Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P29353 and P62993	Pubmed	SVM Score :1.3734031
Like p52shc / p46shc , p66shc is tyrosine phosphorylated upon epidermal growth factor ( EGF ) stimulation , binds to activated EGF receptors ( EGFRs ) and forms stable complexes with Grb 2 . 1.3734031^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.82289871
However , TC 45 inhibited the EGF induced association of p52Shc with Grb 2 , which was attributed to the ability of the PTP to recognize specifically p52Shc phosphorylated on Y 239 . 0.82289871^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.92407099
The NH ( 2 ) terminal proline rich collagen homology 2 ( CH 2 ) domain of p66shc associates with full length grb 2 in vitro via the COOH terminal src homology 3 ( C SH 3 ) domain of grb 2 . 0.92407099^^^ This relationship between p66shc , grb 2 , and sos 1 provides a novel mechanism for the activation of rac1 . . 0.56779146^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.56373806
Interaction of Shc with Grb 2 regulates the Grb 2 association with mSOS . 0.56373806^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.93191548
EGF induced association of Shc with the adapter protein Grb 2 may have implications for activation of the p21ras signaling pathway in the intestine . 0.93191548^^^ The association of Grb 2 with Shc increased fourfold and fivefold . 0.67045154^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.73142269
The SLF dependent association between Grb 2 and Shc in nontransformed cells involved formation of a complex of Grb 2 with c kit receptor after SLF treatment . 0.73142269^^^ In contrast to p210bcr abl transformed cells , in which there was constitutive tight association between Grb 2 and Shc , binding between Grb 2 and Shc was Steel factor ( SLF ) dependent in a SLF responsive , nontransformed parental cell line . 0.65334068^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.53936632
Treatment of PC 12 cells expressing either wild type or the Y766F mutant with aFGF led to tyrosine phosphorylation of Shc , the association of Shc with GRB 2 , a shift in the electrophoretic mobility of the Ras guanine nucleotide releasing factor , Sos ( son of sevenless ) , and enhancement in mitogen activated protein kinase phosphorylation . 0.53936632^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.82204553
Previous studies have demonstrated that GRB 2 directly interacts with Shc , a proto oncogene product that is tyrosine phosphorylated upon receptor and nonreceptor PTK activation . 0.82204553^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :2.1789802
These analyses reveal a hierarchy of interactions between Grb 2 and Shc with the EGFR and indicate that Grb 2 can bind the tyrosine phosphorylated EGFR directly , as well as indirectly via Shc . . 2.1789802^^^ Since Grb 2 also binds Shc after EGF stimulation , we investigated whether Y 1173 is a binding site for the SH 2 domain of Shc on the EGFR . 0.56959915^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.78949368
Shc interacted with tyrosine phosphorylated p 150 via its SH 2 domain , and the Grb 2 SH2 domain likewise bound tyrosine phosphorylated Fms and p 150 . 0.78949368^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.65755825
Following tyrosine phosphorylation by either receptor or non receptor tyrosine kinases , Shc may interact with the adaptor protein Grb 2 , which is linked to Sos 1 , a guanine nucleotide exchange factor for human ras . 0.65755825^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.57768126
By contrast , tyrosine phosphorylation of Shc protein and phospholipase C gamma as well as interaction of Grb 2 protein with Shc and SOS protein signaling components are unaltered in the TM 1 infected cells . 0.57768126^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.59575929
Interaction of Shc with Grb 2 regulates association of Grb 2 with mSOS . 0.59575929^^^ The following observations support a role for Shc in regulating the Grb 2 : mSOS association : ( 1 ) a phosphopeptide corresponding to the sequence surrounding Tyr 317 of Shc , which displaces Shc from Grb 2 , abolished the enhanced association between Grb 2 and mSOS ; and ( 2 ) addition of phosphorylated Shc to unactivated T cell lysates was sufficient to enhance the interaction of Grb 2 with mSOS . 0.51890982^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.93571914
However , Grb 2 was shown to associate rapidly with SHC proteins in a GH dependent manner . 0.93571914^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :1.1882493
In contrast , the dissociation of SOS from Grb 2 did not affect the interactions between Grb 2 and tyrosine phosphorylated Shc . 1.1882493^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.59072792
Similarly , more Grb 2 was associated with Shc than with EGFR after EGF stimulation . 0.59072792^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.57799867
These effects require the association of Shc with Grb 2 . 0.57799867^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :1.0744613
In this communication , we demonstrate that the Shc proteins are phosphorylated on tyrosine residues and are complexed with Grb 2 and the chicken EGFR following ligand activation of this receptor . 1.0744613^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.81868148
We conclude that Shc serves as a primary docking protein for GRB 2 in smooth muscle cells and is critical for proliferation in response to PDGF . . 0.81868148^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.51207784
However , expression of IRS 1 increased the extent of Grb 2 associated with IRS 1 with a concomitant reduction in the amount of Grb 2 associated with Shc . 0.51207784^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.72944026
SHC is phosphorylated on tyrosine and associates with GRB 2 in MT transformed cells . 0.72944026^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :1.0627214
From these results , we conclude that after insulin and EGF treatment , Shc associates with both Grb 2 and mSOS and therefore may mediate , at least in part , insulin and EGF induced activation of p21ras . 1.0627214^^^ These results indicate that the association of Grb 2 nSOS with Shc may be an important event in insulin induced , mSOS mediated activation of p21ras . . 0.809093^^^ Shc proteins are phosphorylated on tyrosine residues and associate with growth factor receptor bound protein 2 ( Grb 2 ) upon treatment of cells with epidermal growth factor ( EGF ) or insulin . 0.79109849^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.51182325
Importantly , 3 13 fold more Grb 2 was associated with Shc than with IRS 1 . 0.51182325^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.61529127
Complex formation between Trk and SHC , SHC tyrosine phosphorylation , and association of SHC with Grb 2 were mediated by autophosphorylation at Y 490 in Trk [ sequence : see text ] . 0.61529127^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.53572724
The shc oncogene product is tyrosine phosphorylated by Src family kinases and after its phosphorylation interacts with the adapter protein Grb 2 ( growth factor receptor bound protein 2 ) . 0.53572724^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.79303488
Taken together , these data demonstrate that interruption of the interaction between Shc and the endogenous Grb 2 by the delta N Grb 2 impairs the oncogenic signaling of the activated p 185 , indicating that ( 1 ) the delta N Grb 2 functions as a strong dominant negative mutant , and ( 2 ) Shc / Grb2 / Sos pathway plays a major role in mediating the oncogenic signal of the activated p 185 . 0.79303488^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.52575382
In these cells , activated HERRet induces tyrosine phosphorylation of Shc , complex formation of Shc with Grb 2 and Sos and activation of p21ras . 0.52575382^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :1.4690706
Here we show that Shc is tyrosine phosphorylated and associates with Grb 2 in 5 Abl transformed cells , whereas Shc in NIH3T3 cells is phosphorylated solely on serine and is not Grb 2 associated . 1.4690706^^^ A necessary downstream element of Abelson murine leukemia virus ( Ab MLV ) mediated transformation is Ras , which can be activated by the phosphotyrosine dependent association of Shc with the Grb 2 mSos complex . 0.58630513^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.54528236
Stimulation via the T cell growth factor interleukin 2 ( IL 2 ) leads to tyrosine phosphorylation of Shc , the interaction of Shc with Grb 2 , and the Ras GTP / GDP exchange factor , mSOS . 0.54528236^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.51037828
FcgammaRI cross linking induces the tyrosine phosphorylation of Shc ; tyrosine phosphorylated Shc binds to Grb 2 forming a Shc Grb 2 complex . 0.51037828^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.56271815
Surprisingly , however , despite the EGF induced decrease in the amount of Grb 2 SOS bound to Shc , the extent of Grb 2 associated with Shc remained constant , and there was a concomitant increase in the amount of SOS associated with Grb 2 . 0.56271815^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.66007081
Interaction between Grb 2 and p120cbl increases threefold following EGF treatment of cells ; in vitro , this induction of Grb 2 association with unphosphorylated p120cbl can be mimicked by the addition of tyrosine phosphorylated Shc , suggesting a transfer of information between the SH 2 and SH 3 domains of Grb 2 . 0.66007081^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.92629685
As in Shc , N Shc can bind activated EGF receptor , become tyrosine phosphorylated , and form a complex with Grb 2 adapter protein following EGF stimulation . 0.92629685^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.83003081
Although Grb 2 also associated with tyrosine phosphorylated Shc , there was no detectable interaction of CrkII with Shc . 0.83003081^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.56100848
We have previously reported that tyrosine phosphorylation of Shc and its association with the Grb 2 Sos complex may contribute to the activation of the mitogen activated protein kinase pathway by gastrin . 0.56100848^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.628047
It is also shown that Shc is associated with the adaptor protein Grb 2 . 0.628047^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.61608924
This resulted in an increased association of IRS 1 with the p 85 subunit of phosphatidylinositol 3 kinase , increased phosphatidylinositol 3 kinase activity in anti IRS 1 immunoprecipitates , constitutive activation of p 70 S6 protein kinase , and an increased association of Grb 2 with Shc in the absence of ligand . 0.61608924^^^ By contrast , association of Grb 2 with Shc and activation of MAPK , but not the p 70 S6 kinase , could be stimulated by epidermal growth factor or platelet derived growth factor . 0.57969306^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.54532253
Mutagenesis studies indicate that Y239 / 240 make an important contribution to the association of Shc with Grb 2 . 0.54532253^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.66114908
The association of Shc with GRB 2 by IGF 1 was detected by immunoblot with anti Shc antibody but was hardly visible with antiphosphotyrosine antibody , which was in marked contrast to efficient tyrosine phosphorylation of Shc by EGF . 0.66114908^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.59178946
Shc stimulates Ras / mitogen activated protein kinase ( MAPK ) through forming a complex with Grb 2 at the phosphorylated tyrosine ( Y ) residue 317 . 0.59178946^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.74669023
GH promoted the rapid , transient association of SHC with the Grb 2 SOS complex , which correlated with the time course of Ras , Raf , and MEK activation . 0.74669023^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :1.0516513
We previously observed that this stimulation condition is associated with a reduction in the interaction of Grb 2 with phosphorylated Shc , an enhanced interaction of Shc with SHIP , and a block in the Ras signaling pathway . 1.0516513^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.73169319
Surprisingly , only the gel shifted 66 kDa Shc isoform ( serine / threonine phosphorylated ) was tyrosine phosphorylated and associated with Grb 2 . 0.73169319^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.78590941
Like growth factor induced Shc phosphorylation , which leads to the association of Shc with Grb 2 , TPA also induced this association , but , correspondingly to the above results , the TPA induced association was disrupted by in vitro treatment of the Shc immunoprecipitate with PP 1 . 0.78590941^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.57799867
UTP also promoted the association of Shc with Grb 2 . 0.57799867^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.66855521
Ang 2 rapidly induced phosphorylation of Shc and association of Shc with Grb 2 . 0.66855521^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :2.0282413
In addition , Shc bound to the activated EGF receptor via the PTB domain dominantly interacts with Grb 2 Sos complex and plays a major role in the Ras signaling pathway . . 2.0282413^^^ Shc R397K was coprecipitated with the QM 1148 and QM 1173 receptors , was tyrosine phosphorylated , and associated with Grb 2 and Sos . 0.86009173^^^ In cells expressing the QM 1173 receptor , Shc R175K was tyrosine phosphorylated and associated with Grb 2 , while association of Sos was barely detectable . 0.77059196^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.56699898
Following an infusion of insulin , Shc was found to associate with GRB 2 . 0.56699898^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.66245984
Tyrosine phosphorylation of Shc allowed for enhanced interactions between Shc and Grb 2 as identified by coimmunoprecipitation experiments . 0.66245984^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.95587963
We provide evidence that SLP 76 , Cbl , and Shc are tyrosine phosphorylated on FcgammaRI receptor stimulation and are associated with the adapter protein Grb 2 in gamma interferon differentiated U 937 cells ( U937IF ) . 0.95587963^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :1.044813
In addition , 14 , 15 EET SI administration stimulated tyrosine phosphorylation of src homologous and collagen like protein ( SHC ) and association of SHC with both growth factor receptor binding protein ( GRB 2 ) and EGFR . 1.044813^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.67787775
Collectively , these results suggest that the association of Shc with Grb 2 is essential for IGF 1 mediated neurite outgrowth , whereas the IRS 2 Grb 2 phosphatidylinositol 3 ' kinase complex may regulate growth cone extension and membrane ruffling . . 0.67787775^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.88156774
The interactions between Shc , Grb 2 , and SHIP are therefore analogous to the interactions between Shc , Grb 2 , and SOS . 0.88156774^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.62168707
In FGF 2 treated proliferating EC , FRS 2 as well as Shc are tyrosine phosphorylated and interact with Grb 2 . 0.62168707^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.52485746
Our results also show that shear stress induced an association of alphavbeta 3 and beta 1 integrins with Shc , and an attendant association of Shc with Grb 2 . 0.52485746^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :1.321174
Among upstream signaling molecules of ERK , Shc was constitutively associated with Grb 2 and was not tyrosine phosphorylated by GM CSF and FMLP , and Sos 1 and c Raf 1 were not phosphorylated by GM CSF , IL 3 , TNF , and FMLP in monocytes , whereas all these signaling molecules were affected and / or utilized by GM CSF in MO7e cells . 1.321174^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.75512154
Although overexpression of SHIP 2 did not affect insulin induced tyrosine phosphorylation of the insulin receptor beta subunit and Shc , subsequent association of Shc with Grb 2 was inhibited , possibly by competition between the SH 2 domains of SHIP 2 and Grb 2 for the Shc phosphotyrosine . 0.75512154^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.8877598
Shc then associates with growth factor receptor bound protein 2 ( Grb 2 ) , an adaptor protein and extracellular signal regulated kinase . 0.8877598^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.5862305
Stimulation of FcalphaRI induced the tyrosine phosphorylation of Shc and increased the association of Grb 2 with Shc and CrkL . 0.5862305^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.6959384
Coexpression of Cas with 5 Src enhanced the association of Grb 2 with the adapter protein Shc and the protein tyrosine phosphatase Shp 2 ; coexpression of Shc or Shp 2 mutants significantly reduced SRE activation by Cas and 5 Src . 0.6959384^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.5917227
Intact actin filaments appear to be essential for mediation of early events such as association of Shc with Grb 2 in response to insulin , which leads to stimulation of gene expression . 0.5917227^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.58343031
But , further upstream , phosphorylation of syk and of shc and inducible association between shc and Grb 2 were not affected . 0.58343031^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.76063206
Phosphorylated Shc binds to Grb 2 which forms a complex with Sos guanine nucleotide exchange factor for p21ras . 0.76063206^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.52269836
By contrast , ethanol had no effect on Shc phosphorylation when measured up to 1 h , and did not affect the association of Grb 2 with Shc . 0.52269836^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :1.3355616
Whereas SHC bound to RET was associated with GRB 2 and GAB 1 proteins , SNT / FRS2 was associated with GRB 2 only , suggesting that SNT / FRS2 is involved mainly in the activation of the RAS / mitogen activated protein kinase ( MAPK ) pathway but not the phosphatidylinositol 3 kinase ( PI 3 K ) / AKT pathway . 1.3355616^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.60070266
Of the subsequent intracellular signaling pathways , PDGF induced PDGF beta receptor association with PLC gamma was not affected , whereas tyrosine phosphorylation of Shc , subsequent association of Shc with Grb 2 , and MAP kinase activation were relatively decreased . 0.60070266^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.70867698
The tyrosine phosphorylation of IGF IR , IRS 2 , Shc , and p42 / p44 MAP kinase ( MAPK ) , and the association of Grb 2 with Shc , were examined by immunoprecipitations and Western blotting . 0.70867698^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.91688091
Shc protein has been shown to directly induce the association with growth factor receptor bound protein 2 and downstream the activation of the mitogen activated protein kinase . 0.91688091^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.58586593
E 2 induced phosphorylation of c Src is associated with increased tyrosine phosphorylation of Shc , increased association of Shc with Grb 2 , and induction of Ras , but not Rap 1 , activation . 0.58586593^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.71237119
To explore the interactions between Grb 2 and phosphorylated ligands , we have solved the crystal structure of complexes between the Grb 2 SH2 domain and peptides corresponding to Shc derived sequences . 0.71237119^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.60243259
Furthermore , Shc tyrosine phosphorylation and its association with Grb 2 were also elevated in small t antigen expressing cells . 0.60243259^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.72485401
In turn , Shc binds Grb 2 and Sos , which results in the rapid activation of MAP kinase . 0.72485401^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.74288975
We finally show that Grb 2 binds to p 60 ( Shc ) in oocytes specifically upon insulin treatment . 0.74288975^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.79005409
The inhibition of IGF 1 induced MAP kinase activation in ErbB 2 overexpressing breast cancer cells is correlated with decreased IGF 1 induced Shc tyrosine phosphorylation , leading to a decreased association of Grb 2 with Shc and decreased Raf phosphorylation . 0.79005409^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.73134752
In turn , Shc binds Grb 2 and Sos , which result in the rapid activation of mitogen activated protein kinase . 0.73134752^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.83033153
In turn , Shc binds Grb 2 and Sos which result in the rapid activation of MAP kinase . 0.83033153^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.72485401
In turn , Shc binds Grb 2 and Sos , which result in the rapid activation of MAP kinase . 0.72485401^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We also show that upon tyrosine phosphorylation , p52shc becomes associated with the adaptor protein , Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Once tyrosine phosphorylated , p52Shc and p46Shc associated with grb 2 . ^^^ Treatment with SLF or IL 3 did increase tyrosine phosphorylation of membrane localized p52Shc , which could then associate with grb 2 , although the majority of tyrosine phosphorylated Shc was located in the cytosol . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Lastly , as has been shown previously with the tyrosine kinase containing receptors for epidermal growth factor , platelet derived growth factor , and insulin , activation of the EpR leads to the association of p52shc with the 25 Kd polypeptide , Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The activation pathway does not directly involve phorbol ester sensitive protein kinase C types , but does require ( 1 ) pertussis toxin sensitive G protein beta gamma subunits , ( 2 ) a staurosporine and genistein sensitive protein kinase , ( 3 ) phosphoinositide 3 ' kinase activity , ( 4 ) activation of Sos in a multimolecular complex that contains p46Shc , and p52Shc , and Grb 2 , ( 5 ) the GTPase p21Ras , and ( 6 ) the protein kinase p74Raf 1 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The results indicated that AlFx dose dependently enhanced the tyr phos of the cell adhesion proteins FAK and paxillin , as well as of the adaptor molecules p46shc , p52shc , and p66shc and their association with GRB 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
After a 4 week follow up a second laparotomy was performed , and the residual pancreas removed . p46Shc , p52Shc and p66Shc , Grb 2 , and p42 / p44 MAP kinase expression and phosphorylation were measured either in freshly isolated pancreatic acinar cells or whole pancreatic extracts . ^^^ Incubating freshly isolated pancreatic acinar cells with bombesin resulted in time and concentration dependent stimulation of p46Shc / p52Shc phosphorylation , Shc Grb 2 complex formation , and p42 / p44 MAP kinase activation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Here we demonstrate that activated EphB 1 recruits the adaptor proteins Grb 2 and p52Shc and promotes p52Shc and c Src tyrosine phosphorylation as well as MAPK / extracellular signal regulated kinase ( ERK ) activation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Cooperation and selectivity of the two Grb 2 binding sites of p52Shc in T cell antigen receptor signaling to Ras family GTPases and Myc dependent survival . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
A second complex , not identified in other models includes tyrosine phosphorylated p66SHC , Grb 2 , RasGAP and p 190 RhoGAP . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
U 46619 also activated signaling proteins upstream of p 21 ras , inducing tyrosine phosphorylation on Shc and complex formation between Shc and growth factor receptor binding protein 2 ( GRB 2 ) . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Furthermore , the SH 2 domain of adaptor protein GRB 2 , but not Shc , associated with the activated RON beta chain , and GRB 2 SOS complexes translocated from the cytosol to the membrane upon MSP treatment . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We have shown that , heat shock activates Raf 1 kinase and causes an increase in phosphotyrosine content of the 52 kDa Shc protein accompanied by an increment in the amount of coimmunoprecipitated Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Both TRH and EGF induced the association of tyrosine phosphorylated Shc proteins with a fusion protein containing SH 2 and SH 3 domains of Grb 2 , another important component in ras activation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
This results in Shc also becoming tyrosine phosphorylated and binding to the SH 2 domain of Grb 2 ( ref . 10 ) . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Specific motifs recognized by the SH 2 domains of Csk , 3BP2 , fps / fes , GRB 2 , HCP , SHC , Syk , and Vav . ^^^ We report here the optimal recognition motifs for SH 2 domains from GRB 2 , Drk , Csk , Vav , fps / fes , SHC , Syk ( carboxy terminal SH 2 ) , 3BP2 , and HCP ( amino terminal SH 2 domain , also called PTP1C and SHPTP 1 ) . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Although several of the protein tyrosine phosphorylations induced by the CNTF / LIF / OSM / IL6 family of factors may correspond to novel tyrosine kinase targets , we have been able to demonstrate the involvement of known signaling molecules , such as phospholipase C gamma , phosphoinositol 3 kinase , phosphotyrosine phosphatase ( PTP1D ) , pp 120 , SHC , GRB 2 , STAT 91 , Raf 1 , and the mitogen activated protein kinases ERK 1 and ERK 2 , revealing substantial convergence not only between the pathways activated by this cytokine family and other cytokines , but with pathways previously known to be activated only by factors that utilize receptor tyrosine kinases . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Stimulation of Jurkat cells with either anti TCR beta or anti CD 3 monoclonal antibody failed to induce substantial tyrosine phosphorylation of Shc proteins or their association with Grb 2 which forms a complex with the guanine nucleotide exchange factor hSOS . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Affinities are in the nanomolar range , the Shc peptide having the highest affinity , followed by peptides mimicking Grb 2 binding sites on EGF and HGF receptors , the putative sites on insulin and IGF 1 receptors having much lower affinities . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Multiple cytokines stimulate the binding of a common 145 kilodalton protein to Shc at the Grb 2 recognition site of Shc . ^^^ We recently reported that interleukin 3 , Steel factor , and erythropoietin all induce the tyrosine phosphorylation of Shc and its association with Grb 2 in hemopoietic cell lines . ^^^ The latter finding , in conjunction with the observations that p 145 does not bind , in vitro , to the Src homology 2 ( SH 2 ) domain of Shc , that it is not present in anti Grb 2 immunoprecipitates , and that a phosphopeptide which blocks the binding of Shc to the SH 2 domain of Grb 2 also blocks the binding of Shc to p 145 , suggests that p 145 contains an SH 2 domain and competes with Grb 2 for the same tyrosine phosphorylated site on Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Both normal and GPI defective lines also displayed a similar 2 to 3 fold increase in phosphorylation of the Shc protein and its association with growth factor receptor bound protein 2 in response to insulin . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
This was paralleled by decreased formation of a complex between the adaptor protein known as growth factor receptor bound protein 2 and SHC . ^^^ These results suggest , for the first time , that TGF beta induces down regulation of Src family kinases , leading to disruption of the SHC growth factor receptor bound protein 2 complex . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Shc is tyrosine phosphorylated in antigen receptor activated T cells and can potentially form a complex with the adapter molecule Grb 2 and could thus recruit the Ras guanine nucleotide exchange protein Sos into the antigen receptor complex . ^^^ The present data show that Grb 2 can bind to the phosphorylated TAM , but this binding is independent of Shc and there is no formation of zeta 1 TAM . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The same antibody to SV 40 T antigen , however , fails to coprecipitate another substrate of IGF IR , the transforming protein Shc , and two other signal transducing molecules , Grb 2 and Sos . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Phosphorylation of Shc on tyrosine residue Y 317 allows binding to the SH 2 domain of Grb 2 , and hence stimulation of the Ras pathway . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Shc phosphorylation in cells following growth factor , insulin , cytokine , and lymphocyte receptor activation leads to its association with Grb 2 and activation of Ras . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Consistent with these differences , Grb 2 predominantly bound to the 52 kDa Shc isoform following insulin stimulation , whereas Grb 2 associated with both the 52 and 46 kDa Shc isoforms after EGF stimulation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Shc is then phosphorylated on tyrosine residues and recruits the adaptor Grb 2 , thereby potentially linking alpha 6 beta 4 to the ras pathway . ^^^ Phenylalanine substitutions at the beta 4 TAM disrupted association of alpha 6 beta 4 with hemidesmosomes , but did not interfere with tyrosine phosphorylation of Shc and recruitment of Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Shc and a novel 89 kDa component couple to the Grb 2 Sos complex in fibroblast growth factor 2 stimulated cells . ^^^ The activated fibroblast growth factor receptor 1 ( FGFR 1 ) expressed in L 6 myoblasts did not bind Grb 2 directly , but indirectly , through the small adaptor protein Shc , which was tyrosine phosphorylated in response to fibroblast growth factor 2 ( FGF 2 ) stimulation . ^^^ FGF 2 stimulation of mutant FGFR 1 expressing cells still allowed formation of complexes containing Shc , Grb 2 , and the nucleotide exchange factor Sos and mediation of a mitogenic signal . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Insulin elicits dissociation of Sos from Grb 2 SH3 domains , whereas EGF signaling is reversed by receptor down regulation and Shc dephosphorylation , releasing Grb 2 SH2 domains . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Rapid tyrosine phosphorylation of Grb 2 and Shc in T cells exposed to anti CD 3 , anti CD 4 , and anti CD 45 stimuli : differential effects of aging . ^^^ Two adapter proteins , Grb 2 and Shc , have recently been implicated in the transmission of activation signals from the stimulated T cell receptor to Ras . ^^^ We show here that in vitro stimulation of mouse splenic T cells with crosslinked anti CD 3 antibody leads within 30 s to phosphorylation of both Grb 2 and Shc . ^^^ Crosslinked anti CD 4 antibody leads to phosphorylation of Shc and to the phosphorylation of a 30 kDa protein that cross reacts with anti Grb 2 antibodies . ^^^ Aging leads to a decline in CD 3 stimulated phosphorylation of Shc ( but not Grb 2 ) , and to an increase in CD 4 stimulated phosphorylation of Grb 2 , Shc , and the 30 kDa Grb 2 like protein . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Ras is activated , the SHC adapter protein is tyrosine phosphorylated and binds GRB 2 , and myc mRNA levels are increased following expression of all kinase active BCR ABL proteins with the exception of the Y177F / R552L / Y793F BCR ABL mutant in 32D cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Binding of the Grb 2 SH2 domain to phosphotyrosine motifs on receptors , or other adaptor proteins such as Shc , recruits this Grb2 / Sos complex at the plasma membrane where Sos stimulates nucleotide exchange on ras , then ras activates raf and leads to MAP kinase activation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
SHC and GRB 2 are constitutively by an epidermal growth factor receptor with a point mutation in the transmembrane domain . ^^^ Among these , the SHC adaptor protein was phosphorylated in absence of EGF , the other adaptor , GRB 2 was constitutively associated with the Glu 627 EGF receptor in vivo and in vitro , and mitogen activated protein kinase was constitutively phosphorylated . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The phosphorylated IRS 1 also associates Grb 2 , as does the phosphorylated Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Shc tyrosine phosphorylation and its binding to Grb 2 were impaired in the A 960 cells and were unaffected by overexpression of IRS 1 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
RTK mediated mitogenic signalling involves a series of SH 2 and SH 3 dependent protein protein interactions between tyrosine phosphorylated receptor , Shc , Grb 2 and Sos , resulting in Ras dependent MAP kinase activation . ^^^ Here we demonstrate that activation of MAP kinase by Gi coupled receptors is preceded by the G beta gamma mediated tyrosine phosphorylation of Shc , leading to an increased functional association between Shc , Grb 2 and Sos . ^^^ Moreover , disruption of the Shc Grb 2 Sos complex blocks G beta gamma mediated MAP kinase activation , indicating that G beta gamma does not mediate MAP kinase activation by a direct interaction with Sos . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We demonstrate that the GRB 2 and SHC cytoplasmic substrates are involved in FLT 4 signal transduction . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We show that phospholipase C gamma 1 , Ras GTPase activating protein , the p 85 subunit of phosphatidylinositol 3 ' kinase , Shc , Grb 2 , Vav , Fyn , and Src are components of the Flk2 / Flt3 signal transduction pathway . ^^^ In addition , we demonstrate that phospholipase C gamma 1 , the p 85 subunit of phosphatidylinositol 3 ' kinase , Shc , Grb 2 , and Src family tyrosine kinases , but not Ras GTPase activating protein , Vav , or Nck , physically associate with the Flk2 / Flt3 cytoplasmic domain . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Phosphorylated Shc could be seen to associate with Grb 2 in a complex which included hSOS . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Two Grb 2 SH2 binding proteins were also characterized in RBL2H3 cells ; the adapter Shc and a 33 kDa molecule . ^^^ Shc is constitutively tyrosine phosphorylated in unstimulated cells and Fc epsilon R 1 ligation induces no changes in its phosphorylation or binding to Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
On the other hand , kinase activation of Src and Raf 1 , phosphorylation of protein tyrosine phosphatase 1D / Syp and Shc , and complex formation with Grb 2 were greatly diminished by suramin . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
After stimulation of the HGF receptor , Shc is phosphorylated on Y317VNV , generating an high affinity binding site for Grb 2 ( Kd = 15 nM ) . ^^^ Thus HGF stimulation can trigger the Ras pathway by recruiting Grb 2 both directly through the receptor , and indirectly , through Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In lymphohemopoietic cells , IL 13 , IL 4 , and insulin failed to induce increased tyrosine phosphorylation of Shc , or its association with grb 2 , modification of Sos 1 , or activation of erk 1 and erk 2 mitogen activated protein kinases , suggesting that p 170 mediates downstream pathways distinct from those mediated by IRS 1 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
One corollary of these phosphorylation events in 5 erbB transformed fibroblasts is the formation of a complex involving SHC , growth factor receptor bound protein 2 , and a novel 75 kDa phosphotyrosyl protein . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Stimulation of smooth muscle cells with angiotensin 2 resulted in tyrosine phosphorylation on Shc proteins and subsequent complex formation between Shc and growth factor receptor binding protein 2 ( GRB 2 ) . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The tyrosine phosphorylation of Jak 2 was accompanied by increased kinase activity , whereas Shc tyrosine phosphorylation induced its association with a 25 kD protein , Grb 2 . ^^^ Thus , our data suggest that Jak 2 , Shc , and Grb 2 may be involved in signal transduction after ligand binding to c mpl in human platelets . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Chromosome locations of genes encoding human signal transduction adapter proteins , Nck ( NCK ) , Shc ( SHC 1 ) , and Grb 2 ( GRB 2 ) . ^^^ Therefore , DNAs from panels of rodent human hybrids carrying defined complements of human chromosomes were assayed for the presence of the cognate genes for NCK , SHC , and GRB 2 , three SH 2 or SH2 / SH3 ( Src homology 2 and 3 ) domain containing adapter proteins . ^^^ The NCK locus is at chromosome region 3q21 , a region involved in neoplasia associated changes ; the SHC cognate locus , SHC 1 , is at 1q21 , and the GRB 2 locus is at 17q22 qter telomeric to the HOXB and NGFR loci . ^^^ Both SHC 1 and GRB 2 are in chromosome regions that may be duplicated in some tumor types . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
A mutant insulin receptor induces formation of a Shc growth factor receptor bound protein 2 ( Grb 2 ) complex and p21ras GTP without detectable interaction of insulin receptor substrate 1 ( IRS 1 ) with Grb 2 . ^^^ Insulin receptors induce p21ras GTP formation by two possible mechanisms : tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and its subsequent association with Grb 2 , or Shc phosphorylation and its subsequent association with Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In contrast to insulin , however , IL 4 failed to induce tyrosine phosphorylation of Shc or association of Shc with GRB 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In contrast , the insulin receptor does not bind Grb 2 directly but rather induces the tyrosine phosphorylation of two proteins , insulin receptor substrate 1 and Shc , that bind the Grb2 / Sos complex . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Shc protein is tyrosine phosphorylated upon B cell receptor ( BCR ) activation and after its phosphorylation interacts with the adaptor protein Grb 2 . ^^^ Tyrosine phosphorylation of Shc and its association with Grb 2 were profoundly reduced in both Lyn and Syk deficient B cells upon BCR stimulation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
GRB 7 can also bind tyrosine phosphorylated SHC , albeit at a lower affinity than GRB 2 binds SHC . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Compartmentalization of SHC , GRB 2 and mSOS , and hyperphosphorylation of Raf 1 by EGF but not insulin in liver parenchyma . ^^^ Following administration of a saturating dose of EGF ( 10 micrograms / 100 g body weight ) , there was a rapid ( t1 / 2 approximately 1 . 1 min ) internalization of receptor coincident with its tyrosine phosphorylation at residue 1173 and receptor recruitment of the adaptor protein SHC , its tyrosine phosphorylation and its association with GRB 2 and the Ras guanine nucleotide exchange factor , mSOS , largely in endosomes . ^^^ This led to a cytosolic pool of a complex of tyrosine phosphorylated SHC , GRB 2 and mSOS . ^^^ While insulin administration ( 15 micrograms / 100 g body weight ) led to insulin receptor beta subunit tyrosine phosphorylation and internalization , there was little detectable tyrosine phosphorylation of SHC , recruitment of GRB 2 , association of a complex with mSOS or any detectable change in the mobility of Raf 1 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Endothelin induces tyrosine phosphorylation and GRB 2 association of Shc in astrocytes . ^^^ To clarify the molecular mechanism responsible for this response , involvement of the adapter proteins , Shc and Grb 2 , has now been investigated . ^^^ It is shown here that in these cells , ET 1 stimulates tyrosine phosphorylation of Shc , resulting in its stable association with Grb 2 but not with Grb 3 3 , a Grb 2 isoform with partially deleted SH 2 domain . ^^^ These results demonstrate that tyrosine phosphorylated Shc specifically interacts with the SH 2 domain of Grb 2 . ^^^ These data strongly suggest that ET 1 induced MAPK activation is a G protein coupled pathway that involves Shc , Grb 2 , and probably Raf 1 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Furthermore , the expression of mutant SH PTP 2 had no effect on the binding of Grb 2 to IRS 1 , on the tyrosine phosphorylation of Shc , or on the formation of the complex between Shc and Grb 2 in response to insulin . ^^^ These results suggest that SH PTP 2 may regulate an upstream element necessary for Ras activation in response to insulin and that this upstream element may be required for the Grb 2 or Shc dependent pathway . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In an interleukin ( IL ) 3 dependent cell line expressing the transfected wild type EpoR , Epo , or IL 3 induced tyrosine phosphorylation of Shc and its association with Grb 2 . ^^^ These results suggest that the carboxyl terminal region of EpoR may play a crucial role in activation of MAP kinases through the Ras signaling pathway which may be activated by tyrosine phosphorylation of Shc and its association with Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In response to EGF treatment , complexes form between Sos , Grb 2 and tyrosine phosphorylated Shc and / or EGF receptor . ^^^ In response to NGF treatment , complexes form between Sos , Grb 2 and tyrosine phosphorylated Shc . ^^^ While Shc is also found bound to the activated NGF receptor , Trk , no complexes were detectable that contained both Trk and Grb 2 or Sos . ^^^ In streptolysin O permeabilised cells , a tyrosine phosphopeptide , EGFR Y1068P , which binds to the SH 2 domain of Grb 2 , totally blocks growth factor induced formation of complexes between Grb 2 and Shc or EGF receptor , and also blocks activation of nucleotide exchange on Ras . ^^^ Higher concentrations of TRK Y490P inhibit tyrosine phosphorylation of Shc and the formation of Shc complexes with Grb 2 : this results in strong inhibition of Ras activation by NGF and partial inhibition of Ras activation by EGF . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The activated FLT 4 tyrosine kinase domain was found to interact with the Src homology 2 domains of the SHC and GRB 2 adaptor proteins in vitro and with SHC in cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
This inhibition of insulin signaling directly correlated with an increased association of Grb 2 with IRS 1 and a concomitant sequestration of Grb 2 away from Shc . ^^^ Consistent with the Shc Grb 2 pathway as the major route for insulin stimulated c Fos and AP 1 transcriptional activation , the IRS 1 mediated inhibition was reversed by transfection with an expression plasmid for Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
B cell antigen receptor cross linking induces phosphorylation of the p21ras oncoprotein activators SHC and mSOS 1 as well as assembly of complexes containing SHC , GRB 2 , mSOS 1 , and a 145 kDa tyrosine phosphorylated protein . ^^^ We have investigated the effects of AgR ligation on three proteins that have been implicated as regulators of Ras : SHC , GRB 2 , and mSOS 1 . ^^^ This correlated with the formation of complexes containing SHC , GRB 2 , mSOS 1 , and an unidentified 145 kDa tyrosine phosphorylated protein . ^^^ By using a GRB 2 fusion protein to probe blots , we showed that SHC was the major protein that GRB 2 bound to in anti Ig stimulated B cells . ^^^ This argues that SHC couples GRB 2 / mSOS1 to the 145 kDa protein and that SHC is likely to be essential for mSOS 1 function in B cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The EGF receptor mutant Dc 214 is able to activate the ras guanine nucleotide exchanger and phosphorylate mitogen activated protein kinase ( MAPK ) , presumable as a result of complex formation between tyrosine phosphorylated SHC and GRB 2 . ^^^ Also , our data show that EGF receptors are able to phosphorylate SHC , activate the exchange of guanine nucleotide on ras and phosphorylate MAPK by a mechanism that does not require receptor autophosphorylation sites and , therefore , the src homology 2 ( SH 2 ) : phosphotyrosine dependent interaction of SHC or GRB 2 with the EGF receptor . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
B cell antigen receptor stimulation induces formation of a Shc Grb 2 complex containing multiple tyrosine phosphorylated proteins . ^^^ Activation of growth factor receptor tyrosine kinases , such as the epidermal growth factor and insulin receptors , induces tyrosine phosphorylation of Shc proteins and their association with the SH 2 domain containing adaptor protein Grb 2 . ^^^ The Shc Grb 2 complex has been implicated in coupling these receptors to p21ras . ^^^ Also , Shc is induced to associate with the Grb 2 molecule and an undefined 130 kDa protein . ^^^ In a specific response to B cell activation , the Shc Grb 2 complex associates with several tyrosine phosphorylated proteins , including two prominent phosphoproteins with molecular masses of 130 and 110 kDa . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Formation of Shc Grb 2 complexes is necessary to induce neoplastic transformation by overexpression of Shc proteins . ^^^ Phosphorylated Shc proteins form a complex with the SH 2 SH3 containing Grb 2 protein which is implicated in the regulation of Ras , suggesting that Shc is involved in the intracellular transmission of growth signals from activated tyrosine kinases to Ras . ^^^ We now report that , in vitro , the high affinity binding of Grb 2 to Shc proteins requires phosphorylation of Shc at Tyr 317 , which lies within the high affinity binding motif for the Grb 2 SH2 domain , pYVNV , where Asn at the +2 position is crucial for complex formation . ^^^ In vivo , Tyr 317 is the major , but not the only , site for Shc phosphorylation , and is the sole Shc high affinity binding site for Grb 2 . ^^^ Mutant Shc proteins with substitution of the Tyr 317 by Phe lose the capacity to be highly phosphorylated on tyrosine upon growth factor receptor activation , to bind Grb 2 and to induce neoplastic transformation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Such polypeptides include Grb 2 , which comprises a single Src homology 2 ( SH 2 ) domain flanked by two SH 3 domains , and the 66 , 52 and 46 kDa Shc proteins which possess an SH 2 domain in their carboxy terminus . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Tyrosine phosphorylated Shc was found to be capable of associating with the SH 2 domain of Grb 2 following IL 2 stimulation . ^^^ These results indicate that tyrosine phosphorylation of Shc and its association with Grb 2 may be important events in IL 2 initiated signal transduction events in T cells . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The oncogenic versions of the Ret and Trk tyrosine kinases bind Shc and Grb 2 adaptor proteins . ^^^ In addition , in cells containing either Ret or Trk oncoproteins , Shc proteins are constitutively phosphorylated on tyrosine and bound to Grb 2 . ^^^ Finally , when proto Trk product is stimulated by NGF , Shc phosphorylation and association with Grb 2 are induced . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Tyrosine phosphorylated Shc , in turn , formed a complex with the signaling molecule Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The Shc GRB 2 complex formed during insulin stimulation is a possible mediator of p21ras and MAP kinase activation in IRS 1 deficient 32 D cells . ^^^ Our results suggest that the Shc GRB 2 complex and the activation of p21ras dependent signaling pathways , including MAP kinase , are insufficient for insulin stimulated mitogenesis and that the essential function ( s ) of IRS 1 in proliferative signaling is largely unrelated to IRS 1 GRB 2 complex formation . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In this study we examine the ability of tyrosine phosphorylated proteins from Jurkat T cells stimulated by CD 2 or T cell receptor CD 3 to interact with the src homology 2 or src homology 3 domains from eight different proteins involved in signal transduction in lymphocytes : Vav , Shc , Nck , phosphatidylinositol 3 kinase , phospholipase C gamma 1 , Ras GTPase activating protein , c Crk and Grb 2 . ^^^ Coimmunoprecipitation experiments support the idea of a trimolecular complex Shc Grb 2 Vav in vivo . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The phosphorylation on tyrosine of SHC and several other GRB 2 associated proteins increased upon stimulation with CSF 1 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In addition , though certain signal transmitters , including Shc and GRB 2 , were recruited by both kinases , EGFR and ErbB 3 elicited tyrosine phosphorylation of distinct sets of intracellular substrates . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Growth factors differentially stimulate the phosphorylation of Shc proteins and their association with Grb 2 in PC 12 pheochromocytoma cells . ^^^ Growth factor receptor tyrosine kinases can form stable associations with intracellular proteins that contain src homology ( SH ) 2 domains , including two proteins , Shc and Grb 2 , that are thought to lie upstream from the ras protooncogene in a signaling cascade . ^^^ NGF and EGF also induced the association of Shc proteins with a Grb 2 fusion protein or endogenous Grb 2 , whereas insulin had no effect . ^^^ All of the tyrosine phosphorylated Shc proteins associated with the Grb 2 fusion protein , although only about half of the endogenous Shc was phosphorylated in response to NGF or EGF . ^^^ Moreover , these growth factors stimulated the association of phosphatidylinositol 3 kinase activity with the Grb 2 fusion protein , although this activity was not detected in anti Shc immunoprecipitates . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
After its phosphorylation , Shc interacted with another adapter protein , Grb 2 , and , via Grb 2 , with the Ras GTP / GDP exchange factor mSOS . ^^^ Thus , during IL 2 signaling , the interaction of Shc with the IL 2R beta chain and its simultaneous association with Grb 2 and mSOS may couple IL 2R stimulation to Ras signaling . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In contrast to the activated epidermal growth factor receptor that binds the GRB 2 Sos complex directly , activation of the insulin receptor results in the interaction of GRB 2 Sos with IRS 1 and Shc , thus linking the insulin receptor to Ras signaling pathways . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The proteins Grb 2 Sem 5 , Shc and Sos have been implicated in the signalling pathway from tyrosine kinase receptors to Ras . ^^^ Sos is also associated with ligand activated tyrosine kinase receptors which bind Grb 2 Sem 5 , and with the Grb 2 Sem 5 binding protein , Shc . ^^^ Sem 5 is homologous to the mammalian protein Grb 2 , which binds the autophosphorylated EGF receptor and other phosphotyrosine containing proteins such as Shc through its SH 2 domain . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The adaptor molecule growth factor receptor bound protein 2 ( Grb 2 ) plays a role in insulin action since it links tyrosine phosphorylated IRS 1 and Shc to the guanine nucleotide exchange factor , Sos , which initiates the mitogen activated protein ( MAP ) kinase cascade by producing Ras GTP . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
After MGDF stimulation , we detect interactions among SHC , grb 2 , SHPTP 1 , SHPTP 2 , and the mpl / JAK2 complex . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The SH 2 domain containing proteins Shc and GRB 2 have been implicated in this latter signaling route . ^^^ Anti Shc antibodies co immunoprecipitated tyrosine phosphorylated 145 kD proteins ( p 145 ) , whereas GRB 2 immunoprecipitates contained phosphorylated Shc , Syp , and proteins of 145 and 90 kD ( p 90 ) . ^^^ In contrast , tyrosine 764 of G CSF R appeared to be exclusively required for tyrosine phosphorylation of Shc and its association with p 145 and GRB 2 . ^^^ In addition , tyrosine 764 also specifically mediated binding of GRB 2 to p 90 without the involvement of Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Phosphorylated Shc subsequently associated with a complex that includes Grb 2 and the p 21 Ras activator , Sos . ^^^ Tyrosine phosphorylation of Shc and subsequent complex formation with Grb 2 and Sos appear to be a common mechanism by which tyrosine kinase receptors and the G / CCKB G protein coupled receptor stimulate the Ras dependent MAP kinase pathway . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The SH2 / SH3 domain containing protein GRB 2 interacts with tyrosine phosphorylated IRS 1 and Shc : implications for insulin control of ras signalling . ^^^ The interactions between GRB 2 and these two proteins require ligand activation of the insulin receptor and are mediated by the binding of the SH 2 domain of GRB 2 to phosphotyrosines on both IRS 1 and Shc . ^^^ Although GRB 2 associates with IRS 1 and Shc , it is not tyrosine phosphorylated after insulin stimulation , implying that GRB 2 is not a substrate for the insulin receptor . ^^^ Furthermore , we have identified a short sequence motif ( YV / IN ) present in IRS 1 , EGFR and Shc , which specifically binds the SH 2 domain of GRB 2 with high affinity . ^^^ We propose a model whereby insulin stimulation leads to formation of multiple protein protein interactions between GRB 2 and the two targets IRS 1 and Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We show that phospholipase C gamma , phosphatidylinositol 3 kinase / p70 S 6 kinase , Shc , Grb 2 , Raf 1 , and mitogen activated protein kinase are downstream components of the Nyk / Mer signal transduction pathways . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
IRL 1620 induced MAPK activation involved the adapter proteins Shc and Grb 2 and the serine / threonine kinase Raf 1 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Transduction of a mitogenic signal from the cell membrane to the nucleus involves the adapter proteins SHC and Grb 2 , which mediate activation of the Ras / mitogen activated protein ( MAP ) kinase pathway . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
UV induces the formation of complexes between activated EGFR and SOS , Grb 2 , PLC gamma , and SHC that can be precipitated with antibodies to EGFR . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
CD 16 mediated p21ras activation is associated with Shc and p 36 tyrosine phosphorylation and their binding with Grb 2 in human natural killer cells . ^^^ The Src homology ( SH ) 2 / SH3 domain containing protein Grb 2 and the oncoprotein Shc have been implicated in a highly conserved mechanism that regulates p21ras activation . ^^^ Shc immunoprecipitates from lysates of CD 16 or IL 2 stimulated NK cells contained Grb 2 and an unidentified 145 kD tyrosine phosphoprotein . ^^^ Grb 2 immunoprecipitates from anti CD 16 stimulated NK cells contained not only Shc , but also a 36 kD tyrosine phosphoprotein ( p 36 ) . ^^^ The interaction between Grb 2 and Shc or p 36 occurred via the Grb2SH2 domain as indicated by in vitro binding assays using a bacteriologically synthesized glutathione S transferase Grb2SH2 fusion protein . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We specifically evaluated whether these compounds affected 2 recently discovered proteins involved in controlling ras function : Shc , which is tyrosine phosphorylated by src and activated growth factor receptors , and Grb 2 , which mediates signal transduction from activated growth factor receptors through ras . ^^^ We evaluated their effects on tyrosine phosphorylation of Shc , binding of Grb 2 to Shc and MAP kinase activity . ^^^ This was accompanied by decreased Shc tyrosine phosphorylation , Shc ' s association with Grb 2 and MAP kinase activity . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The complex formations of Fyn Shc , Shc Grb 2 , and Grb 2 mSOS were detected in the activated Fyn transformed cells , whereas the SH 2 deletion mutant of Fyn failed to form a complex with mSOS . ^^^ These findings support the idea that Fyn activates the activity of mSOS bound to Grb 2 through tyrosine phosphorylation of Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Calcium influx through L type VSCCs leads to tyrosine phosphorylation of the adaptor protein Shc and its association with the adaptor protein Grb 2 , which is bound to the guanine nucleotide exchange factor Sos 1 . ^^^ In response to calcium influx , Shc , Grb 2 , and Sos 1 inducibly associate with a 180 kDa tyrosine phosphorylated protein , which was determined to be the epidermal growth factor receptor ( EGFR ) . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
A second phosphotyrosyl protein we identified , p 140 , associated with the Shc and Grb 2 adapter proteins by direct binding to a novel phosphotyrosine interacting domain located at the N terminus of Shc . and to the SH 3 domains of Grb 2 , respectively . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Sos , Vav , and C3G participate in B cell receptor induced signaling pathways and differentially associate with Shc Grb 2 , Crk , and Crk L adaptors . ^^^ The BCR activates Ras , presumably by the formation of a Shc Grb 2 adaptor complex , which recruits the Grb 2 associated guanine nucleotide exchange factor Sos to the plasma membrane . ^^^ C3G did not bind to either Grb 2 , Shc , or Crk in vivo . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
B cell antigen receptor stimulation and interacts in vivo with Fyn and Syk tyrosine kinases , Grb 2 and Shc adaptors , and the p 85 subunit of phosphatidylinositol 3 kinase . ^^^ Tyrosine phosphorylated Shc , which prominently associated with Grb 2 , was detected in association with Cbl in activated B cells . ^^^ Thus , Grb 2 and Shc adaptors , which associate with immunoreceptor tyrosine based activation motifs , may link Cbl to the B cell receptor . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
HRG also induced the association of GRB 2 with tyrosine phosphorylated p185c erbB 2 , p180erbB 4 and SHC . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In BCR ABL delta 1 40 reactivated by the SH 3 deletion , transphosphoryation of other cellular proteins like p 62 or SHC in vivo and autophosphorylation with recruitment of GRB 2 were also recovered . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Following thrombin stimulation , phosphorylated Shc is recruited to Grb 2 complexes . ^^^ Expression of mutant Shc proteins defective in Grb 2 binding displays a dominant negative effect on thrombin stimulated p 44 MAP kinase activation , gene induction and cell growth . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Interleukin 6 induces tyrosine phosphorylation of the Ras activating protein Shc , and its complex formation with Grb 2 in the human multiple myeloma cell line LP 1 . ^^^ Therefore , we investigated the effects of IL 6 on some recently identified signaling intermediates , Shc ( Src homology and collagen ) and Grb 2 ( growth factor receptor bound protein 2 ) , known to activate p21ras . ^^^ This led to the complex formulation of Shc with Grb 2 , an adaptor protein known to relocate a p21ras GDP exchange factor . ^^^ Taken together , these findings suggest that IL 6 might activate the Ras signaling pathway via tyrosine phosphorylation of Shc and subsequent recruitment of Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Systematic mapping of potential binding sites for Shc and Grb 2 SH2 domains on insulin receptor substrate 1 and the receptors for insulin , epidermal growth factor , platelet derived growth factor , and fibroblast growth factor . ^^^ The specificity characteristics of the SH 2 domains of Grb 2 and Shc are discussed . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Similarly , phosphorylated hSOS 1 was unable to form a complex with Shc through Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Even though epidermal growth factor ( EGF ) also stimulates ERK activity and phosphorylation of SOS similar to insulin , EGF induces a dissociation of the Grb 2 SOS complex from Shc . ^^^ Although EGF stimulation of the mutant EGF receptor activates ERK and phosphorylation of both Shc and SOS , it fails to directly associate with either Shc or Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Association of these mutants with GRB 2 was still observed , suggesting that interaction of p 80 with GRB 2 but not with Shc or IRS 1 was relevant for cell transformation . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The data show that the doubly phosphorylated ITAM all bind the PTK ZAP 70 , but the ITAM also variably bind the PTK p59fyn and the adapters Shc , Grb 2 and the p 85 regulatory subunit of phosphoinositol 3 ' kinase . ^^^ Shc , Grb 2 and p 85 could bind the zeta ITAM and the CD 3 gamma and delta ITAM , but not the CD 3 epsilon ITAM . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The beta gamma subunit of Gi mediates mitogen activated protein ( MAP ) kinase activation through a signaling pathway involving Shc tyrosine phosphorylation , subsequent formation of a multiprotein complex including Shc , Grb 2 , and Sos , and sequential activation of Ras , Raf , and MEK . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Pathways downstream of Shc and Grb 2 are required for cell transformation by the tpr Met oncoprotein . ^^^ Utilizing this mutant , together with additional Tpr Met mutants containing Tyr to Phe substitutions , we have demonstrated that transformation of Fr3T3 fibroblasts by the Tpr Met oncoprotein is dependent upon pathways downstream of Shc and Grb 2 and that pathways downstream of phosphatidylinositol 3 ' kinase , phospholipase Cgamma , and SHPTP2 / Syp are insufficient for transformation . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Antigen receptors on T and B cells activate Ras through a signaling pathway that results in the tyrosine phosphorylation of Shc and the formation of a complex of Shc with the Grb 2 adaptor protein . ^^^ Here we show to the contrary that engagement of FcepsilonRI with antigen leads to increased tyrosine phosphorylation of Shc and the association of Shc with Grb 2 and other proteins ( p 120 and p 140 ) . ^^^ Sos is constitutively associated with Grb 2 in these cells but dissociates from Shc on stimulation with antigen . ^^^ Therefore , the Syk dependent tyrosine phosphorylation of Shc and its association with Grb 2 may provide a pathway through Sos for activation of Ras by FcepsilonRI . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Although IRS 1 is the major substrate of the IGF IR , there is another early phosphotyrosine substrate termed SHC , which also activates Ras via Grb 2 mSos complex . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We conclude that Grb 2 , but not Shc , is involved in T cell receptor signaling . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The heterotrimeric G q protein coupled angiotensin 2 receptor activates p 21 ras via the tyrosine kinase Shc Grb 2 Sos pathway in cardiac myocytes . p 21 ras plays as important role in cell proliferation , transformation and differentiation . ^^^ Ang 2 causes rapid tyrosine phosphorylation of Shc and its association with Grb 2 and mSos 1 , a guanine nucleotide exchange factor of p 21 ras . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
A peptide corresponding to residues 740 762 of the beta 3 cytoplasmic domain was capable of binding the signaling proteins SHC and GRB 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
B cell antigen receptor ( BCR ) stimulation induces tyrosine phosphorylation of the Shc adaptor protein and its association with Grb 2 . ^^^ The Shc / Grb2 complex may be involved in Ras activation , since Grb 2 interacts with the guanine nucleotide exchange factor Sos . ^^^ The 130 kDa molecule inducibly associates with Shc , while the 75 kDa protein interacts with the carboxy terminal SH 3 domain of Grb 2 . ^^^ Cbl constitutively interacts with the SH 3 domains of Grb 2 , with a preference for the amino terminal domain , and is in this way recruited to Shc upon BCR stimulation . ^^^ Immunodepletion studies showed that Grb 2 associated Cbl can be phosphorylated by BCR induced tyrosine kinases independent of a Shc / Grb2 interaction . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Multiple forms of an inositol polyphosphate 5 phosphatase form signaling complexes with Shc and Grb 2 . ^^^ BACKGROUND : Shc and Grb 2 form a complex in cells in response to growth factor stimulation and link tyrosine kinases to Ras during the resulting signaling process . ^^^ Shc and Grb 2 each contain domains that mediate interactions with other unidentified intracellular proteins . ^^^ In vivo studies show that these proteins form signal transduction complexes with Shc and with Grb 2 . ^^^ CONCLUSIONS : These findings strongly implicate the inositol polyphosphate 5 phosphatases in Shc and Grb 2 mediated signal transduction . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Activation of these kinases is independent on protein and mRNA synthesis and is preceded by rapid tyrosine phosphorylation of an adaptor protein p 66 ( Shc ) and formation of a complex between p 66 Shc , a bridging molecule Grb 2 , and a Ras activator , mSos . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Y 577 is also required for association of Shc with GRB 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The Shc proteins have been implicated in the Ras signaling pathway by virtue of their association with the Grb 2 adaptor molecule . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
It has been demonstrated that Bcr Abl interacts with Grb 2 and Shc , which in turn activates the Ras pathway . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Upon ligand binding , the alpha6beta4 integrin becomes phosphorylated on tyrosine residues and combines sequentially with the adaptor molecules Shc and Grb 2 , linking to the ras pathway , and with cytoskeletal elements of hemidesmosomes . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In clones expressing high levels of mutant EGF receptor , the levels of both Grb 2 and SHC were decreased . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Following EGF or insulin stimulation , Shc is phosphorylated on single Tyr 317 residue serving as a docking site for Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The amino acid sequence downstream from tyrosine 1356 represents a consensus binding site for the Grb 2 adaptor protein and forms a multisubstrate binding site for the p 85 subunit of phosphatidylinositol 3 kinase , phospholipase Cgamma , and the Shc adaptor protein . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Involvement of SHC , GRB 2 , SOS and RAS in prolactin signal transduction in mammary epithelial cells . ^^^ Grb 2 and Sos associated with the SHC proteins within 1 3 min of Prl treatment in these mammary cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Enhanced tumorigenic behavior of glioblastoma cells expressing a truncated epidermal growth factor receptor is mediated through the Ras Shc Grb 2 pathway . ^^^ We also show that the truncated EGF receptor constitutively associates with the adapter proteins Shc and Grb 2 which are involved in the recruitment of Ras to activated receptors . ^^^ Several derivatives of DeltaEGFR containing single , or multiple mutations at critical autophosphorylation sites were constructed and used to demonstrate that the major Shc binding site is Tyr 1148 , and that Grb 2 association occurs primarily through Tyr 1068 . ^^^ We conclude that the increased tumorigenic potential of glioblastoma cells expressing the truncated EGF receptor is due at least in part to Ras activation presumably involving the Shc and Grb 2 adapter proteins . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
To assess these two possible pathways , we performed Western blots for Grb 2 in anti Shc and anti IRS 1 immunoprecipitates and found that 5 fold more Grb 2 was associated with Shc than with IRS 1 after either IGF 1 or insulin stimulation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In contrast , Shc , phosphatidylinositol 3 kinase ( Pl3K ) , Grb 2 , and Ras GTPase activating protein ( GAP ) bound with different affinities to the bis or monophosphorylated peptides , while the Src family protein tyrosine kinase ( PTK ) Fyn did not bind specifically to any of the tested peptides . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Cholecystokinin stimulates formation of shc grb 2 complex in rat pancreatic acinar cells through a protein kinase C dependent mechanism . ^^^ We therefore compared the effects of CCK and epidermal growth factor ( EGF ) on Tyr phosphorylation of the adaptor proteins Shc and its association with Grb 2 and the guanine nucleotide exchange factor SOS . ^^^ CCK stimulated tyrosyl phosphorylation of Shc as well as Shc Grb 2 complex formation was significant at 2 . 5 min , maximal at 5 min , and persisted for at least 30 min . ^^^ These results suggest that formation of an Shc Grb 2 SOS complex via a PKC dependent mechanism may provide the link between Gq protein coupled CCK receptor stimulation and Ras activation in these cells . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In addition , another adaptor protein , Shc , may bind to GRB 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Upon phosphorylation , Shc proteins form stable complexes with cellular tyrosine phosphorylated proteins and with the Grb 2 adaptor protein . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In addition to the reported Shc and 145 kDa phosphoproteins , a prominent 90 95 kDa phosphoprotein resembling CD 19 was detected in the Grb 2 complexes . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
BACKGROUND : The 5 abl oncogene of the Abelson murine leukemia virus ( A MuLV ) encodes a cytoplasmic tyrosine kinase that can associate with phosphoinositide 3 kinase , Shc and Grb 2 , and activate the pathway that leads from Ras to mitogen activated protein ( MAP ) kinase . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
SHIP is constitutively tyrosine phosphorylated and associated with Shc and Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Co immunoprecipitation analyses showed that autophosphorylated STK / RON associated with PLC gamma , P 13 kinase , Shc and Grb 2 in both transfectants . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We provide evidence that a class of integrins combines with the adaptor Shc and thereby with Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
However , insulin treatment of CHO T cells markedly increased the PI 3 , 4 , 5 P 3 5 ' phosphatase activity associated with Shc and Grb 2 . ^^^ The insulin regulated polyphosphoinositide 5 ' phosphatase was not immunoreactive with antibody raised against the recently cloned SHIP 5 ' phosphatase reported to associate with Shc and Grb 2 in B lymphocytes . ^^^ These data demonstrate that insulin causes formation of complexes containing a PI 3 , 4 , 5 P 3 5 ' phosphatase , and Shc or Grb 2 , or both , suggesting an important role of this enzyme in insulin signaling . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The Grb 2 SH2 domain binds to Tyr 1068 of EGFR and Tyr 317 of Shc while its SH 3 domains bind to mSos 1 . ^^^ Therefore , EGF treatment potentially results in the formation of several multimeric signaling complexes , including EGFR Grb 2 mSos1 , EGFR Shc Grb 2 mSos1 , and Shc Grb 2 mSos1 , linking the receptor to activation of the Ras GTPase . ^^^ An EGFR derived phosphopeptide bound Grb 2 with a KD of 0 . 7 microM , whereas the Shc derived phosphopeptide bound Grb 2 with a KD of 0 . 2 microM . ^^^ Grb 2 mSos1 bound to both EGFR and Shc derived phosphopeptides with higher affinities ( KD of 0 . 3 microM and 31 nM , respectively ) than Grb 2 alone . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
IL 3 stimulates tyrosine phosphorylation of the Shc adaptor protein and thereby formation of a complex of Shc with Grb 2 at phosphorylated tyrosine ( Y ) residue 317 Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Epidermal growth factor ( EGF ) stimulated Ras activation involves specific interactions between the EGF receptor ( EGFR ) , the adaptor proteins Grb 2 and Shc , and the nucleotide exchange factor Sos 1 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Tyrosine phosphorylated beta and gamma ITAM peptides immobilized on beads precipitated Syk , Lyn , Shc , Grb 2 , and phospholipase C gamma 1 from lysates of rat basophilic leukemia RBL 2H3 cells . ^^^ Phospholipase C gamma 1 , Shc , and Grb 2 were precipitated only by the diphosphorylated beta ITAM peptide . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Moreover we found that , upon SCF stimulation , the Grb2 / c Cbl complex recruits Shc , probably via Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The increase observed in the phosphotyrosine content of the 52 kDa Shc protein , accompanied by an increased amount of co immunoprecipitated Grb 2 , and the activation of Raf 1 kinase provide evidence of the involvement of a Ras Raf dependent pathway , with a time course that is similar to that of ERK activation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Moreover , in contrast to the normal c Mpl receptor , this same mplY599F mutant was also incapable of stimulating TPO dependent Shc phosphorylation , the association of Shc with Grb 2 or c Mpl and of inducing c fos expression . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Complexes are formed between Fms and other signal transduction proteins such as Grb 2 , Shc , Sos 1 , and p 85 . ^^^ The p 150 is phosphorylated on tyrosine , and forms a complex with Shc and Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We report here the effects of AG 957 on the physical state of p210bcr abl and its signaling adapter molecules Shc and Grb 2 in K 562 cells . ^^^ Material suggesting the involvement of p210bcr abl in high molecular weight complexes also appears using anti Shc , anti Grb 2 and anti phosphotyrosine antibodies . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Signaling from PI3Kgamma to MAPK appears to require a tyrosine kinase , Shc , Grb 2 , Sos , Ras , and Raf . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Ras activation in HeLa cells at mid G 1 phase was dependent on RNA and protein synthesis and was not associated with tyrosine phosphorylation of Shc proteins and their binding to Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Also , the major tyrosine phosphorylated proteins that associate with Grb 2 in erbB 2 over expressing cancer cells appear to be erbB 2 and Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Taxol induces tyrosine phosphorylation of Shc and its association with Grb 2 in murine RAW 264 . 7 cells . ^^^ We investigated a possible effect of taxol on tyrosine phosphorylation of Shc and on formation of the Shc / Grb 2 complex in the murine macrophage like cell line RAW 264 . 7 . ^^^ Non denatured Shc containing protein complexes were immunoprecipitated with anti Shc antibody , and analysis with an anti Grb 2 antibody revealed the presence of the 24 kDa Grb 2 protein . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
BCR mediated Shc phosphorylation and recruitment of Grb 2 depended on CD 45 expression . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Negative signaling in B cells causes reduced Ras activity by reducing Shc Grb 2 interactions . ^^^ In contrast , the association of Shc and Grb 2 was abrogated under negative and induced under positive signaling conditions . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
This was accompanied by the tyrosine phosphorylation of Shc and the formation of complexes between Shc and the adapter protein Grb 2 . ^^^ Thus , these receptors exhibit mechanistic differences in their coupling to Ras signaling , and HRG beta 2 administration triggers multiple inputs into the Ras signaling pathway , involving receptor Grb 2 , receptor Shc , and Shc Grb 2 complexes . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Further analysis indicated that treatment with IFN beta disrupted IL 6 induced binding of PTP1D / Syp to gp 130 and the adaptor protein Grb 2 ; IFN beta pretreatment also interfered with IL 6 induced interaction of Shc with Grb 2 and a 145 kD tyrosine phosphorylated protein . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Stimulation of Gi coupled lysophosphatidic acid and alpha2A adrenergic receptors or overexpression of Gbeta1gamma2 subunits leads to tyrosine phosphorylation of the Shc adapter protein , which then associates with tyrosine phosphoproteins of approximately 130 and 180 kDa , as well as Grb 2 . ^^^ These data suggest that Gbetagamma subunit mediated activation of Src family nonreceptor tyrosine kinases can account for the Gi coupled receptor mediated tyrosine phosphorylation events that direct recruitment of the Shc and Grb 2 adapter proteins to the membrane . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In this respect , it shares some aspects of signaling with growth factor and cytokine receptors , including activation of phospholipase C gamma , src , and ras ; association of shc with grb 2 ; and stimulation of the Jak / STAT pathway . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Here we report that components of the Ras / Raf / MAPK pathway are constitutively activated in these lck transformed immature thymoblasts . p 56 ( lck ) utilizes Shc and Grb 2 adaptors to mediate activation of p 21 ( ras ) in the thymoblast lines by promoting tyrosine phosphorylation of the Shc protein and constitutive interaction between Shc and Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In summary , FGFR 3 signaling pathway utilizes two GRB 2 containing complexes ; Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
RET alternate splicing influences the interaction of activated RET with the SH 2 and PTB domains of Shc , and the SH 2 domain of Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
A tyrosine phosphorylated protein of 140 kD is constitutively associated with the phosphotyrosine binding domain of Shc and the SH 3 domains of Grb 2 in acute myeloid leukemia cells . ^^^ Our results implicate Shc , Grb 2 , p 140 , and additional tyrosine phosphorylated proteins of 61 and 200 kD in signalling of acute myeloid leukemia cells . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Shc is phosphorylated on Tyr 317 , which serves as a docking site for Grb 2 . ^^^ Insulin induced Shc phosphorylation and subsequent association with Grb 2 was enhanced in WT Shc cells . ^^^ Although 317Y / F Shc was also able to interact with insulin receptor , decreased amounts of Shc phosphorylation and Shc association with Grb 2 were observed in 317Y / F Shc cells , indicating that 317Y / F Shc functions as a dominant negative mutant . ^^^ These results indicate that Shc Tyr 317 phosphorylation plays an important role , via coupling with Grb 2 and competition with IRS 1 , in signal transduction to MAP kinase by insulin , ultimately leading to mitogenesis in Rat 1 fibroblasts . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Ligation of alpha6beta4 in primary human keratinocytes caused tyrosine phosphorylation of Shc , recruitment of Grb 2 , activation of Ras and stimulation of the MAP kinases Erk and Jnk . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
This observation led to our hypothesis that the non phosphorylated Tyr 317 containing region of Shc might have specific affinity for the Grb 2 protein . ^^^ We show here that cell permeable peptides encompassing the Shc Tyr 317 region , 312FDD PSYVNVQNL 323 , can bind to the SH 2 domain of Grb 2 regardless of the state of tyrosine phosphorylation . ^^^ The non phosphorylated Shc peptides with single point mutations at Asp 313 , Asp 314 , or Tyr 317 are inactive , suggesting that these residues play an important role in Grb 2 protein recognition . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Tyrosine phosphorylation of EGF receptor ( EGFR ) , Shc , and phospholipase C gamma 1 ( PLC gamma ) , and growth factor receptor binding protein 2 ( Grb 2 ) coprecipitation with EGFR and Shc were analyzed by Western blotting . ^^^ Grb 2 binding to EGFR was suppressed , but EGF induced Shc tyrosine phosphorylation and Grb 2 association with Shc were not significantly decreased . ^^^ CONCLUSIONS : Long term ethanol feeding suppressed EGF induced receptor autophosphorylation in rat hepatocytes with differential inhibition of downstream signaling processes mediated by PLC gamma , Shc , and Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Antisense src expression inhibits tyrosine phosphorylation of Shc and its association with Grb 2 and Sos which leads to MAP kinase activation in U 937 human leukemia cells . ^^^ The amounts of Grb 2 and Sos co immunoprecipitated with Shc were decreased after Dexa treatment . ^^^ Taken together with all these findings , it is suggested that c Src directly phosphorylates Shc on tyrosine residues , which in turn binds to Grb 2 constitutively associated with Sos to form a Shc Grb 2 Sos complex , and that the complex formation is coupled with MAP kinase activation mediated by Ras activation in U 937 cells . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Examination of the early signaling events of PDGF action revealed that DHS did not affect PDGF induced autophosphorylation of the growth factor receptor or phosphorylation of the SH2 / SH3 adaptor protein Shc and its association with Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Signaling factors that associate with activated erythropoietin ( Epo ) receptor complexes include phospholipase C gamma , phosphatidylinositol 3 kinase , SHIP , Shc , Grb 2 , Cbl , Crk l , HCP , Syp , and STAT 5 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Activation of ERK 1 and 2 may involve the Src homology 2 containing proteins Shc and Grb 2 . ^^^ Following IL 6 stimulation , Shc physically associated with Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Expression of wild type and Phe 925 FAK , but not Phe 397 FAK , enhanced p 130 ( Cas ) association with FAK , Shc tyrosine phosphorylation , and Grb 2 binding to Shc after FN stimulation . ^^^ FN induced Grb 2 Shc association is another pathway leading to activation of ERK 2 via Ras . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Shc contains two Grb 2 binding sites needed for efficient formation of complexes with SOS in B lymphocytes . ^^^ Previous work has shown that tyrosine phosphorylated Shc forms complexes with another adapter protein , Grb 2 , and the Ras guanine nucleotide exchange factor SOS . ^^^ Here , we demonstrate that phosphorylation of Shc by the hematopoietic cell specific tyrosine kinase Syk induces binding of Grb 2 to Shc , suggesting that Syk phosphorylates Shc in stimulated B cells . ^^^ Surprisingly , Syk phosphorylated Shc possesses two Grb 2 binding sites rather than the one site that has been previously reported . ^^^ Both of these sites are required for efficient formation of Shc Grb 2 SOS complexes in vitro and in vivo . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Furthermore , the mutated IGF IRs did not alter Grb 2 association with phosphorylated IRS 1 and SHC . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Previously , it has been demonstrated that Bcr Abl interacts with Grb 2 and Shc , which in turn activates the Ras pathway . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We and others have shown that the Bcr Abl oncoprotein binds activators of the Ras pathway such as Grb 2 and Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The 100 kDa protein did not appear to bind directly to Fms , Ship , Cbl , Shc , or Grb 2 , although all of these proteins were coimmunoprecipitated with p 85 after M CSF stimulation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The PDGF induced association of downstream signaling proteins , including phosphoinositide 3 kinase ( PI 3K ) , growth factor receptor binding protein 2 ( GRB 2 ) , SH 2 domain and collagen like ( Shc ) and phospholipase Cgamma ( PLCgamma ) , with VSMC PDGF receptors was also blocked as a result of the inhibition of PDGF stimulated receptor autophosphorylation by PD 089828 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Consistent with this observation , pp 55 selectively binds to isolated SH 2 domains of Lck , Lyn , Src , and Fyn but not to the SH 2 domains of ZAP 70 , Syk , Shc , SLP 76 , Grb 2 , phosphatidylinositol 3 kinase , and c abl in vitro . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Gi mediated activation of the Ras / MAP kinase pathway involves a 100 kDa tyrosine phosphorylated Grb 2 SH3 binding protein , but not Src nor Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
One of these peptides , bearing the Y * ENW motif , bound the Grb 2 SH2 domain with a threefold higher affinity than the peptide motif Y * VNV derived from the natural ligand Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Since G / CCKB receptor occupancy leads to the activation of the phospholipase C ( PLC ) / protein kinase C ( PKC ) pathway , we examined whether PKC stimulation and Ca2+ mobilization contribute to the phosphorylation of Shc proteins and their association with Grb 2 in response to gastrin . ^^^ Our results indicate that Shc proteins are tyrosine phosphorylated and associate with Grb 2 in response to phorbol esters , suggesting that activation of PKC is a potential signalling pathway leading to activation of the Shc / Grb2 complex . ^^^ Inhibition of PKC by GF109203X completely blocked the effect of PMA on Shc tyrosine phosphorylation and its subsequent association with Grb 2 , but had a partial inhibitory effect on the response to gastrin . ^^^ Depletion of the intracellular Ca2+ pools by treatment with thapsigargin blocked the increase in intracellular free calcium concentration induced by gastrin and diminished the ability of the peptide to stimulate Shc phosphorylation and recruitment of Grb 2 . ^^^ In addition , removal of extracellular Ca2+ partially inhibited the effect of gastrin on Shc phosphorylation as well as its association with Grb 2 , indicating that the effects of gastrin are also mediated by Ca2+ dependent mechanisms . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
APS bound to Shc irrespective of stimulation and bound to Grb 2 after stimulation , suggesting that it plays a role in linkage from BCR to Shc / Grb2 pathway . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In NIH 3T3 cells expressing MT , p 52 Shc carrying the F198V mutation is weakly phosphorylated and does not bind MT or Grb 2 . ^^^ This was found to be due to the ability of Shc 1 260 to become tyrosine phosphorylated and bind Grb 2 . ^^^ Furthermore , full length Shc in which Tyr239 / Tyr240 had been mutated to phenylalanine did not become tyrosine phosphorylated or bind Grb 2 but did inhibit colony formation in soft agar . ^^^ Conversely , p 52 Shc carrying a mutation in the other tyrosine phosphorylation site , Tyr 317 , became heavily tyrosine phosphorylated , bound Grb 2 , and gave rise to colonies in soft agar . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Tyrosine 1356 forms a multisubstrate binding site for the Grb 2 and Shc adaptor proteins , the p 85 subunit of phosphatidylinositol 3 ' kinase , phospholipase Cgamma , and a phosphatase , SHP 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
For EGF induced mitogen activated protein kinase activation in 293T cells , both Shc PTB and SH 2 domains are essential for optimal activation , indicating that a mechanism independent of Grb 2 engagement with Shc may exist . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
While each of these transforming mutants displayed Ras dependent signaling , the transforming activity of two of these mutants was correlated with their ability to bind either the GRB 2 or SHC adapter molecules that couple receptor tyrosine kinases to the Ras signaling pathway . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Present studies demonstrate that EGF induces the co immunoprecipitation of phospholipase C ( PLC ) gamma 1 with the adaptor protein GRB 2 and the guanine nucleotide exchange factor Sos , but not with the adaptor protein SHC , in WB cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
HBx induced the association of Ras upstream activating proteins Shc , Grb 2 , and Sos and stimulated GTP loading onto Ras , but without directly participating in complex formation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Further characterization of these tyrosine phosphorylated molecules revealed that Shc , Grb 2 , and SOS form a complex with the activated FLT 4 receptor . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The first peak of activation of p21ras , at 2 5 min , is mediated by immediate association of phosphorylated Shc with the guanosine exchange factor Sos 1 via the adaptor protein Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Synthetic G 1 peptide blocks Grb 2 SH2 domain association ( IC 50 10 25 microM ) with a 9 amino acid pTyr containing peptide derived from the SHC protein ( pTyr 317 ) . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
MAb induced cell differentiation correlated with p185HER2 phosphorylation , recruitment of Shc and Grb 2 transducer molecules into complexes , and MAPK phosphorylation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Under these conditions , SH 2 domains from PLCgamma , PI 3 kinase , SHC , and Grb 2 did not bind p 62 . ( 4 ) Tryptic phosphopeptide maps of the Nck and the GAP associated p 62 proteins are identical . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In contrast to receptors that themselves have tyrosine kinase activity , the signalling pathways leading to MAP kinase activation that are triggered by growth hormone are poorly understood , but appear to be mediated by the proteins Grb 2 and Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Characterization of Ret Shc Grb 2 complex induced by GDNF , MEN 2A , and MEN 2B mutations . ^^^ The results showed that all of them induce a signal transducing complex consisting of Ret , Shc , and Grb 2 proteins . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
This complex consists of Src homologous collagen protein ( Shc ) , growth factor receptor binding protein 2 ( Grb 2 ) , son of sevenless ( Sos ) , and a novel tyrosine phosphorylated form of the cytoskeletal regulatory protein caldesmon . ^^^ The tyrosine phosphorylation of caldesmon , and its association with the Shc Grb 2 Sos signaling complex directly links tyrosine kinase oncogenic signaling events with cytoskeletal regulatory processes , and may define one mechanism regulating actin stress fiber disassembly in transformed cells . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Furthermore , whereas gastrin stimulated phosphorylation of Shc proteins and association with Grb 2 , activation of the HDC promoter was not influenced by expression of dominant negative Ras ( N 15 or N 17 ) proteins . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We have previously demonstrated that CD 16 ligation promotes complex formation between tyrosine phosphorylated shc and Grb 2 , leading to activation of ras signaling pathway in human NK cells . ^^^ Our data show that , while engagement of both receptors induces tyrosine phosphorylation of shc and Grb 2 recruitment , shc SH2 / receptor complex association is evident only in CD 16 zeta but not in CD 16 gamma transfectants . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In this report , using a constitutively activated Ret TK form , Ret ptc 2 , we demonstrate that the MEN 2B as the activated WT Ret TK binds to several SH 2 signalling proteins such as Shc , Grb 2 , Phospholipase Cgamma , Crk and Nck . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
VEGF induced stimulation of KDR results in the association and phosphorylation of the 46 , 52 , and 66 kDa isoforms of Shc and the induction of Shc Grb 2 complex formation . ^^^ In a similar fashion , KDR associates with Grb 2 and Nck in a ligand dependent fashion , suggesting Shc , Grb 2 , and Nck as potential candidates involved in the regulation of endothelial function . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In serum starved cells this results in EGF receptor autophosphorylation and the recruitment of Grb 2 , Shc and Sos 1 but does not induce a corresponding increase in MAP kinase activity . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Stimulation of PDGFR ' s and EGFR ' s induced tyrosine phosphorylation of the Shc adaptor protein and its association with Grb 2 , suggesting a mechanism by which Ras may be activated in human malignant astrocytoma cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
SHC was tyrosine phosphorylated in response to Fc gamma RI stimulation of U937IF cells and bound to the SH 2 domain of GRB 2 in a stimulation dependent manner . ^^^ In fusion protein pull down experiments the interaction of SHC with the SH 2 domain of GRB 2 was increased in PTPase inhibitor pretreated U937IF cells in response to Fc gamma RI stimulation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Interleukin 5 signals through Shc and Grb 2 in human eosinophils . ^^^ A second adapter protein , Grb 2 , coimmunoprecipitated with Shc following IL 5 stimulation of eosinophils . ^^^ These data suggest that IL 5 activates a signal transduction pathway utilizing the adapter proteins Shc and Grb 2 in the human eosinophil . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Furthermore , IL 2 stimulation increased the level of interaction of phosphorylated Cbl with the p 85 SH2 domains , and we provide evidence that the preformed Cbl Grb 2 complex recruits the phosphorylated p 52 Shc adaptor protein . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In contrast , no change is observed in insulin stimulated Shc tyrosine phosphorylation , or in the association of this substrate with Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Expression of Shc family protein ( Shc / ShcA , SCK / ShcB and N Shc / ShcC ) and Grb 2 mRNAs in the hypoglossal motoneurons after axotomy was examined by in situ hybridization . ^^^ Expression levels of SCK , another Shc family member , and Grb 2 were unaffected by nerve injury . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Novel recruitment of Shc , Grb 2 , and Sos by fibroblast growth factor receptor 1 in 5 Src transformed cells . ^^^ Instead , there was a strong constitutive association of FGFR 1 with the adaptor proteins Shc and Grb 2 and the Ras guanine nucleotide exchange factor Sos . ^^^ Association with Shc and Grb 2 and Sos was not observed in response to FGF . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We also identified a significant increase in the phosphotyrosine content of the 52 kDa Shc protein , accompanied by an increase in Shc coimmunoprecipitated Grb 2 , which suggests the Ras involvement by PRL . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Because Shc interacts with MEN 2 forms of Ret , and because phosphorylation of Shc results in Grb 2 recruitment and subsequent signaling through Ras and Raf , the potential interaction between Ret / ptc2 and Shc was investigated . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Shc phosphorylation and Grb 2 association after EGF treatment were present throughout all phases of growth . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In the present study , we found Ang 2 rapidly induced the tyrosine phosphorylation of the epidermal growth factor ( EGF ) receptor and its association with Shc and Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
CD 16 mediated activation of phosphatidylinositol 3 kinase ( PI 3K ) in human NK cells involves tyrosine phosphorylation of Cbl and its association with Grb 2 , Shc , pp 36 and p 85 PI 3K subunit . ^^^ In addition , we detected the presence of the Grb 2 associated tyrosine phosphorylated p 36 and Shc proteins in anti Cbl and anti p 85 immunoprecipitates from CD 16 stimulated NK cell lysates . ^^^ Upon CD 16 stimulation , Pl 3K activity was found associated with Cbl and to a lesser extent with Grb 2 and Shc as well as with the zeta chain of the CD 16 receptor complex . ^^^ Overall these results suggest that the formation of a complex containing either Shc or pp 36 associated with Grb 2 , Cbl and the p 85 subunit of Pl 3K is one of the major mechanisms which might couple CD 16 to the Pl 3K pathway in NK cells . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
FN stimulation of NIH 3T3 fibroblasts promotes c Src and FAK association in the Triton insoluble cell fraction , and the time course of FN stimulated ERK 2 activation paralleled that of Grb 2 binding to FAK at Tyr 925 and Grb 2 binding to Shc . ^^^ In vitro , FAK directly phosphorylated Shc Tyr 317 to promote Grb 2 binding , and in vivo Grb 2 binding to Shc was observed in herbimycin A treated fibroblasts after FN stimulation . ^^^ Interestingly , c Src in vitro phosphorylation of Shc promoted Grb 2 binding to both wild type and Phe 317 Shc . ^^^ Surprisingly , expression of Phe 925 FAK with Phe 317 Shc also did not block signaling to ERK 2 , whereas FN stimulated signaling to ERK 2 was inhibited by coexpression of an SH 3 domain inactivated mutant of Grb 2 . ^^^ Our studies show that FN receptor integrin signaling upstream of Ras and ERK 2 does not follow a linear pathway but that , instead , multiple Grb 2 mediated interactions with Shc , FAK , and perhaps other yet to be determined phosphorylated targets represent parallel signaling pathways that cooperate to promote maximal ERK 2 activation . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
This method measures directly the binding of a 3H labeled phosphopeptide derived from the sequence around tyrosine 317 in the human Shc ( SpYVNVK ) to the SH 2 domain of Grb 2 , which is precoated as glutathione S transferase fusion proteins on solid phase . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The proximal C terminus ( residues 461 670 ) binds to GRB 2 constitutively , and under conditions of receptor activation binds to the tyrosine phosphorylated SHC adapter molecule . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
However , Ras is activated , Shc is tyrosine phosphorylated and binds to Grb 2 in the tetramerization domain deleted BCR ABL expressing hematopoietic cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Here we show that CD 43 specific activation of human T lymphocytes induced tyrosine phosphorylation of the adaptor protein Shc and of the guanine exchange factor Vav , as well as the formation of a macromolecular complex that comprises Shc , GRB 2 , and Vav . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Moreover , insulin / IGF 1 markedly increased the amount of Grb 2 associated SHC proteins by the same extent . ^^^ Our results suggest that both IRS 1 and IRS 2 are required for phosphatidylinositol 3 kinase activation that leads to adipogenic and thermogenic differentiation of fetal brown adipose tissue ; meanwhile , IRS 1 and SHC , but not IRS 2 , associate with Grb 2 leading to the ras mitogen activated protein kinase signaling pathway required for fetal brown adipocyte proliferation . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Both Shc and IRS 1 associate with Growth Factor Receptor Bound protein 2 ( Grb 2 ) , an adaptor molecule . ^^^ Since dynamin constitutively associates with Grb 2 , it could be recruited to the insulin signaling complex through binding of Grb 2 to tyrosine phosphorylated Shc . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Arachidonic acid mediates angiotensin 2 effects on p21ras in renal proximal tubular cells via the tyrosine kinase Shc Grb 2 Sos pathway . ^^^ Furthermore , Ang 2 caused rapid tyrosine phosphorylation of Shc and its association with Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Negative signaling through SHIP appears to inhibit the Ras pathway through SH 2 domain competition with Grb 2 and Shc and may involve consumption of intracellular lipid mediators that act as allosteric enzyme activators or that promote entry of extracellular Ca2+ . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Furthermore , it prevented insulin or 5 ras induced adipocytic differentiation , utilizing a protein kinase C independent pathway . m 1 stimulation did not alter the phosphorylation state of the insulin receptor substrates IRS 1 and SHC , nor the recruitment of Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Dominant negative forms of SHP 2 had no effect on EGF stimulated interaction of GRB 2 with EGFR or SHC , nor did they influence phosphorylation of SHC and SHC / EGFR association . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
CSF 1 induced the de novo recruitment of Cbl , STAT 3 , STAT5a , STAT5b , p 85 , SHP 1 , Shc , vimentin , and Grb 2 to complexes and caused pre existing complexes involving Vav , elongation factor 1alpha , and F actin to increase in size . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Matrigel induced long lasting tyrosine phosphorylation of Shc , with recruitment of Grb 2 and microtubule associated protein kinase ( MAPK ) activation in both parental NP 31 and NP 31 transformed by ts 5 Ras , which was blocked by anti beta 1 integrin antibody . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Immunoprecipitation was performed with antisera to signal transducers and activators of transcription 1 ( STAT 1 ) , STAT 3 , Janus kinase 1 ( Jak 1 ) , Shc , Grb 2 , Sos 1 , and HGF receptor ( met ) . ^^^ Phosphorylated HGF receptor coimmunoprecipitated with Shc , Grb 2 , and Sos 1 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Growth factor derived mitogenic signals from the cell surface are transmitted to the nucleus via receptor tyrosine kinases ( RTKs ) , the adaptor proteins Shc and Grb 2 , and a Ras dependent protein kinase cascade that activates the extracellular signal regulated kinase ( ERK ) subfamily of mitogen activated protein kinases . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Thus , we examined the interactions of various SH 2 containing molecules like PLC gamma 1 , rasGAP , p 85 subunit of PI 3 kinase , Src , Fyn , Crk , Nck , Grb 2 and Shc with HEK 2 using in vitro binding assays , immunoprecipitations and yeast Two Hybrid assays . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The failure to activate Shc is accompanied by a downstream deficiency in recruitment of Grb 2 and subsequent mitogen activated protein kinase activation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Only the CH domain , which contains the two Grb 2 binding sites on Shc , was phosphorylated by ZAP 70 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Western blot analysis demonstrated that the concentrations of IRS 1 , Shc , GRB 2 , SOS , Syp , PI 3 kinase , MAP kinase and Gi alpha were at least 10 fold higher in cell surface derived , caveolin enriched fraction than in a cell surface derived , caveolin poor fraction ( i . e . , the plasma membranes ) . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We propose a model whereby the association of Grb 2 with CD 28 occurs via an inducible SH 3 mediated interaction and leads to the recruitment of tyrosine phosphorylated proteins such as p 52 ( shc ) bound to the SH 2 domain of Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
These receptor and substrate phosphorylation create binding sites for SH 2 containing signaling molecule , such as Grb 2 , Shc , PI 3 kinase and SHP 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In both cases , ErbB 1 coupled to the adaptor protein Shc , but only when activated by EGF was it able to interact with Grb 2 . ^^^ ErbB 2 binding to peptides containing the Src homology 2 domain of Grb 2 or p 85 and the phosphotyrosine binding domain of Shc varied according to the mode of receptor activation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In all of the tumor cell lines , EGF caused an association between Shc and Grb 2 , another adapter protein linked to cellular ras activation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We show that phosphorylation of tyrosine 490 , but not 785 , of Trk is essential for activation of both Ras and PI 3 kinase in vivo , correlating with tyrosine phosphorylation of Shc and binding of Shc to the adaptor Grb 2 and the Ras exchange factor Sos . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
AG 1478 , a tyrphostin selective for the EGF receptor , reduced the activation of MAP kinase , the tyrosine phosphorylation of SHC , the association of Grb 2 with SHC , and the tyrosine phosphorylation of the EGF receptor and p 120 ( cbl ) but did not block the tyrosine phosphorylation of RAFTK . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The subsequent release of the Grb 2 MEKK1 complex from Shc proteins correlates with JNK activation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Shc is subsequently phosphorylated at tyrosine 317 and recruits Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Overexpression of Slap by this method inhibited DNA synthesis induced by PDGF and serum , whereas overexpression of the adaptor proteins Grb 2 and Shc did not . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Gbetagamma mediated mitogen activated protein kinase activation is mediated by activation of phosphoinositide 3 kinase , followed by a tyrosine phosphorylation event , and proceeds in a sequence of events that involve functional association among the adaptor proteins Shc , Grb 2 , and Sos . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Here we demonstrate that the BCR induced ERK activation is reduced by loss of Grb 2 or expression of a dominant negative form of Ras , RasN 17 , whereas this response is not affected by loss of Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
However , in intact cells , the interaction of Grb 2 with the two short and long Ret isoforms expressed separately is of similar strength , thus suggesting that Ret short isoform interaction with Grb 2 could be mediated not only by Shc but also by a molecule that binds preferentially to this isoform . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Immunoprecipitation / Western blot studies revealed that CCh stimulated tyrosine phosphorylation of the EGF receptor ( EGFr ) and increased co immunoprecipitation of the adapter proteins , Shc and Grb 2 , with the EGFr . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Increased Pyk 2 tyrosine phosphorylation paralleled the time course of Grb 2 binding to Shc and activation of ERK 2 in FAK cells . ^^^ Significantly , repression of endogenous Src family PTK activity by p 50 ( csk ) overexpression inhibited FN stimulated cell spreading , Pyk 2 tyrosine phosphorylation , Grb 2 binding to Shc , and ERK 2 activation in the FAK but not in FAK+ cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Under these conditions , insulin induced Ras activation was also abolished , and Grb 2 association with the Src and collogen homologous ( Shc ) molecule was inhibited without inhibition of the tyrosine phosphorylation of Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
This correlates with a specific inability to achieve high levels of p 66 ( SHC ) tyrosyl phosphorylation and association of p 66 ( SHC ) with GRB 2 , despite high levels of EGF receptor ( EGFR ) autophosphorylation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In contrast to receptor tyrosine kinases , the signalling pathways leading to MAP kinase activation by GH are poorly understood but appear to involve Grb 2 and Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Moreover , tyrosine phosphorylation of Gab 1 correlated with the binding of several SH 2 containing signaling proteins to Gab 1 including Shc , Grb 2 , phosphatidylinositol 3 kinase , and the SHP 2 tyrosine phosphatase . ^^^ In contrast , the Grb 2 SH2 domain did not bind directly to Gab 1 but instead to the Shc and SHP 2 associated with Gab 1 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Shc is phosphorylated on Tyr 239 / 240 and / or Tyr 317 , which serves as a docking site for Grb 2 . ^^^ Insulin induced Shc phosphorylation and subsequent association with Grb 2 was enhanced in wild type ( WT ) Shc cell . ^^^ These results indicate that Shc Tyr 317 is more predominant insulin induced phosphorylation site than Tyr 239 / 240 for coupling with Grb 2 leading to MAP kinase activation and mitogenesis in Rat 1 fibroblasts . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Direct binding of Shc , Grb 2 , SHP 2 and p 40 to the murine granulocyte colony stimulating factor receptor . ^^^ In this report , we show rapid phosphorylation of Shc upon stimulation of NFS 60 cells with G CSF , and inducible association of Shc and Grb 2 with the G CSF R in these cells . ^^^ Using a tyrosine phosphorylated GST G CSF R fusion we demonstrate that Shc , Grb 2 and SHP 2 directly bind the receptor via their respective SH 2 domains , suggesting multiple routes of MAPK activation from the G CSF R are possible . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In particular , following activation of a receptor protein tyrosine kinase ( RPTK ) , proteins like Shc and Grb 2 bind to phosphotyrosine residues of stimulated receptors , thereby activating downstream components of specific signalling pathways . ^^^ Early data obtained in non neuronal cells have revealed that Shc and Grb 2 proteins are highly expressed and activated in all cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Both the c Src and c Fyn tyrosine kinases are tyrosine phosphorylated and activated by cellular hGH stimulation and form part of the multiprotein signaling complex as does tensin , paxillin , IRS 1 , the p 85 subunit of phosphatidylinositol 3 kinase , C3G , SHC , Grb 2 , and Sos 1 . c Cbl and Nck are also tyrosine phosphorylated by cellular stimulation with hGH and associate with the p 130 ( Cas ) CrkII complex . c Jun N terminal kinase / stress activated protein kinase ( JNK / SAPK ) is activated in response to hGH in accordance with the formation of the abovementioned signaling complex , and hGH stimulated JNK / SAPK activity is increased in CrkII overexpressing NIH3T3 cells compared with vector transfected NIH3T3 cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Phosphorylation of Shc tyrosine residues 239 and 317 leads to recruitment of the Grb 2 Sos complex , thus linking Shc phosphorylation to Ras activation . ^^^ The binding specificity of the Gads SH 2 domain is similar to Grb 2 and mediates the interaction of Gads with Shc , Bcr Abl and c kit . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Actinomycin D , C 2 and 7 , inhibitors of Grb 2 SHC interaction produced by Streptomyces . ^^^ Actinomycin D , C 2 and 7 , cyclic peptides , inhibited Grb 2 SH2 domain association ( IC 50 5 7 microM ) with a phosphotyrosine containing peptide derived from the Shc protein ( pTyr 317 ) . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Phosphorylation of a number of substrates such as GAP , GRB 2 , SHC , FES , CRKL , and paxillin is considered a decisive step in transformation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We also found that the chronic activation of the adapter protein is correlated with the binding of Shc to Grb 2 and with defects in the downregulation of mitogen activated protein kinases . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The roles of these substrates as signaling molecules for GH were further demonstrated by the finding that GH stimulated the association of IRS 1 / 2 with phosphatidylinositol 3 kinase , Grb 2 , and phosphotyrosine phosphatase and of Shc with Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
On the other hand , adapter molecules such as Shc , GRB 2 , and SHP 2 have been shown to link the cytokine receptors to Ras , followed by the activation of the Raf MEK MAP kinase pathway , leading to the activation of various transcription factors in the nucleus . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The Arg 1152 > Gln mutant did not signal Shc phosphorylation or Shc Grb 2 association in intact L 6 cells , while binding Shc in a yeast two hybrid system and phosphorylating Shc in vitro . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Association of Shc , Cbl , Grb 2 , and Sos following treatment with 2 , 3 , 7 , 8 tetrachlorodibenzo p dioxin in primary rat hepatocytes . c Src kinases and p 21 Ras are known to be implicated in 2 , 3 , 7 , 8 tetrachlorodibenzo p dioxin ( TCDD ) mediated signal transduction . ^^^ The present study is designed to clarify whether TCDD modulates the molecular interactions of Shc , Cbl , Grb 2 , and Sos in primary rat hepatocytes . ^^^ Interestingly , TCDD decreases the tyrosine phosphorylation level of Cbl , although Cbl recruits more Grb 2 and Shc proteins by TCDD . ^^^ These results indicate that TCDD modulates the molecular interaction of adaptor complex proteins including Shc , Grb 2 , Sos , and Cbl . ^^^ Furthermore , tyrosine phosphorylation of Cbl may not be critical for interaction of the protein with Grb 2 and Shc in the TCDD signaling pathway in primary rat hepatocytes . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The levels of PI 3 kinase , GLUT 4 , p 70 S6 kinase and Ras mRNA were significantly increased by 89 , 40 , 38 , and 47 % , respectively , with running training ; however , the Nck mRNA level was decreased by 24 % . mRNA levels of SHP 2 , Grb 2 , Sos , Shc , GAP , p 62 and p 90 S6 kinase were unaltered by running training . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Over expression of ErbB 2 also resulted in the ligand independent constitutive association between Shc and another adaptor protein , Grb 2 , indicating that receptor activation was sufficient to activate downstream signalling pathways . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The insulin receptor substrate ( IRS ) , SHC , GRB 2 , CRKII and CRKL adaptor proteins have all been implicated in transmitting signals to the nucleus of the cell . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In cardiac fibroblasts , angiotensin 2 activates ERKs through a pathway including the Gbetagamma subunit of Gi protein , Src family tyrosine kinases , Shc , Grb 2 and Ras , whereas Gq and protein kinase C are important in cardiac myocytes . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Furthermore , signaling molecules such as the adaptor proteins Shc and Grb 2 , and the small G protein Rho , also reside within these microdomains . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We also show that NGF induces tyrosine phosphorylation of Shc and its association with Grb 2 . ^^^ Vav and Ras with the adaptor proteins Shc and Grb 2 appear to serve as a link between different receptor mediated signaling pathways and , in human B cells , may play an important regulatory role in neuroimmune interactions . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
BACKGROUND : The adaptor protein Gads is a Grb 2 related protein originally identified on the basis of its interaction with the tyrosine phosphorylated form of the docking protein Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Activation of muscarinic receptors with carbachol was found to inhibit EGF induced signaling , including tyrosine phosphorylation of the adaptor protein Cbl and of the EGF receptor , and complex formation between Shc proteins and the EGF receptor and Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In a second pathway , independent of IRS 1 , GRB 2 links the insulin receptor to Ras signaling through another adapter protein , called Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
After macrophage colony stimulating factor ( M CSF ) stimulation of FDC P 1 ( Fms ) myeloid cells , both 145 and 135 kD SHIP forms were tyrosine phosphorylated and could be coimmunoprecipitated with antibodies to Shc and Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Although the mutated receptor had lost its ability to recruit and / or activate known signaling molecules , such as GRB 2 , SHC , GAB 1 , and PI3K , by using a sensitive association kinase assay we found that the mutated receptor can still associate and phosphorylate a approximately 250 kDa protein . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In cardiac fibroblasts , Ang 2 activated MAP kinase through a pathway including the Gbetagamma subunit of Gi protein , Src , Shc , Grb 2 , and Ras , while Gq and protein kinase C were important in cardiac myocytes . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Flt 3 signaling involves tyrosyl phosphorylation of SHP 2 and SHIP and their association with Grb 2 and Shc in Baf3 / Flt3 cells . ^^^ Like the chimeric murine Flt 3 , human Flt 3 undergoes autophosphorylation , associates with Grb 2 , and leads to tyrosine phosphorylation of Shc on ligand binding . ^^^ These results demonstrate that SHP 2 and SHIP are important components in the human Flt 3 signaling pathway and suggest that SHP 2 and SHIP , by forming complexes with adapter proteins Grb 2 and Shc , may modulate MAP kinase activation , which may be necessary for the mitogenic signaling of Flt3 . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In contrast , EGFR truncation did not impair EGF mitogenic signaling , and in c ' 1000 cells EGF was able to stimulate the association of ErbB 2 with GRB 2 and SHC . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
While the function of Shc in the activation of the Ras pathway via binding to Grb 2 has been well characterized , it is becoming increasingly apparent that Shc participates in additional signaling pathways through interactions with other cytoplasmic proteins . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Multiple binding sites in the growth factor receptor Xmrk mediate binding to p59fyn , GRB 2 and Shc . ^^^ Examination of the Xmrk carboxyterminus for putative tyrosine autophosphorylation sites revealed the presence of potential binding motifs for GRB 2 as well as for Shc . ^^^ The GRB 2 and Shc interactions with the receptor could be disrupted individually by phosphotyrosine peptides containing putative Xmrk autophosphorylation sites , indicating direct binding of both proteins . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
PKC was required for maximal activation of mitogen activated kinase kinase 1 , Raf 1 , and Ras , tyrosine phosphorylation of Shc , and Shc association with Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The need for Shc in this process is however unclear since Grb 2 can be recruited directly to phosphotyrosine containing membrane receptors through its src homology 2 domain . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Shc was also inducibly tyrosine phosphorylated and bound to Grb 2 after Fc gammaRI stimulation of the macrophages . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Grb 2 association with SHC and mitogen activated protein kinase ( MAPK ) activity was also enhanced in response to IGF 1 stimulation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Although insulin receptors and SHC were present in forebrain cortex , there was no increase in their phosphorylation , nor was there any recruitment of GRB 2 following stimulation with insulin . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Pyk 2 induced activation of Src is necessary for phosphorylation of Shc and p130Cas and their association with Grb 2 and Crk , respectively , and for the activation of ERK and JNK cascades . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Analysis of signaling pathways downstream of these tyrosines suggested a positive role for STAT 3 activation in both differentiation and survival signaling , whereas SHP 2 , Grb 2 and Shc appear important for proliferation signaling . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Although high affinity interaction required the presence of at least two of the four YXXM motifs in mIRS 3 , there was not a requirement for specific YXXM motifs . mIRS 3 also bound to SHP 2 , Grb 2 , Nck , and Shc , but less strongly than to p 85 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
A small pool of CSF 1R formed a multimeric complex with phosphatidylinositol 3 kinase ( PI 3 kinase ) , SHP 1 , Grb 2 , Shc , c Src , Cbl , and a significant number of tyrosine phosphorylated proteins in CSF 1 stimulated cells . ^^^ The major pool of activated CSF 1R formed transient multimeric complexes with distinctly different tyrosine phosphorylated proteins , which included STAT 3 but also PI 3 kinase , Shc , SHP 1 , and Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The paradigm for activation of Ras and extracellular signal regulated kinase ( ERK ) / mitogen activated protein ( MAP ) kinase by extracellular stimuli via tyrosine kinases , Shc , Grb 2 , and Sos does not encompass an obvious role for phosphoinositide ( PI ) 3 kinase , and yet inhibitors of this lipid kinase family have been shown to block the ERK / MAP kinase signalling pathway under certain circumstances . ^^^ The concentrations of EGF for which PI 3 kinase inhibitors block Ras activation induce formation of Shc Grb 2 complexes but not detectable EGF receptor phosphorylation and do not activate PI 3 kinase . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Activation of p 125 ( FAK ) was accompanied by its increased association with adapter proteins GRB 2 , Shc , and nonreceptor type tyrosine kinase p 60 ( c src ) . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
To better understand the role of Shc in the oncogenesis by point mutation activated neu ( p185 * ) , we transfected a Shc mutant ( ShcdeltaCHI ) , which lacks the Grb 2 binding site Y 317 by deletion of collagen homology domain 1 , into p185 * transformed NIH3T3 cells . ^^^ We also found that ShcdeltaCH 1 could associate with p185 * ; however , this association did not interfere with the endogenous Shc p185 * interaction or the Shc Grb 2 interaction . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
FAK associates with several different signaling proteins such as Src family PTKs , p130Cas , Shc , Grb 2 , PI 3 kinase , and paxillin . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In addition , ZAS induced the tyrosine phosphorylation of the SHC proteins and their association with GRB 2 , suggesting a role for this complex in the activation of the ERK pathway . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In contrast to what we observed in the AR42J cells , G 17 failed to stimulate MAPK activation and Shc tyrosyl phosphorylation and association with the adapter protein Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Since Ras activation requires the assembly of a multiprotein complex , we examined the effect of carbachol and EGF on tyrosyl phosphorylation of Shc and its association with Grb 2 and the guanine nucleotide exchange factor Sos . ^^^ Grb 2 association with Shc was demonstrated by blotting Grb 2 immunoprecipitates with an anti Shc antibody . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We therefore hypothesized a competition model in which the SH 2 domain of SHIP competes with that of Grb 2 for binding to phospho Shc to inhibit the Ras pathway . ^^^ Second , under conditions of negative signaling leading to SHIP Shc interaction in wild type B cells , we observed a profound reduction in the activation induced association of Grb 2 to Sos . ^^^ Experiments reported here and elsewhere revealed the Grb 2 Sos interaction required the engagement of the Grb 2 SH2 domain by phospho Shc . ^^^ Third , we demonstrated that phospho Shc can not concomitantly bind Grb 2 and SHIP , indicating that the two proteins competed for the same phospho tyrosine residue on Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Here , we show that hypoxia induced tyrosine phosphorylation of p 125 ( FAK ) and paxillin and that hypoxia induced activation of p 125 ( FAK ) was accompanied by its increased association with adapter proteins Shc and GRB 2 , and non receptor type tyrosine kinase p 60 ( c src ) . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Immunoblotting of p 185 ( neu ) containing microvillar fractions revealed the presence in each of stably associated Shc , Grb 2 , Sos , Ras , Raf , mitogen activated protein kinase kinase , and mitogen activated protein kinase / extracellular signal regulated kinase , as well as the transcription factor phosphorylating kinase Rsk . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We found that CSR induced the activation of FAK and Src and the association of FAK and Shc , a signaling molecule linking growth factor receptor tyrosine kinase and Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
This inhibitor has been obtained by rational drug design and is specific toward the Grb 2 SH2 vs . other SH 2 domains and the PTB domain of SHC in vitro . ^^^ Accordingly , CGP 78850 blocks epidermal growth factor receptor ( EGFR ) Grb 2 and Shc Grb 2 interactions in living cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
AP 1510 treatment induced tyrosine phosphorylation of ErbB 1 and ErbB 2 homodimers and recruitment of Src homology 2 domain containing proteins ( Shc and Grb 2 ) . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Insulin stimulation of Shc association with Grb 2 , which is important for p21ras MAP kinase activation , was decreased by overexpression of WT and 2F SHIP . ^^^ Importantly , insulin induced Shc 10 Grb 2 association was not detectably reduced in deltaSH 2 SHIP cells . ^^^ In accordance with the extent of Shc association with Grb 2 , insulin induced MAP kinase activation was relatively decreased in both WT SHIP and 2F SHIP cells , but not in deltaSH 2 SHIP cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Two adaptor molecules , Grb 2 and Shc , have been implicated in the extracellular signal regulated kinase ( ERK ) activation by receptor tyrosine kinases such as the epidermal growth factor receptor ( EGFR ) . ^^^ Here we show that the EGF mediated ERK activation is abolished by loss of Grb 2 , whereas this response is not affected by loss of Shc . ^^^ Conversely , the EGF mediated c Jun N terminal kinase ( JNK ) activation is dependent on Shc , but not Grb 2 . ^^^ These findings strongly support distinct roles for Grb 2 and Shc in controlling ERK and JNK activation after EGF stimulation . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In cardiac fibroblasts AngII activated MAP kinase via G beta gamma subunit of Gi , Src , Shc , Grb 2 , and Ras , whereas Gq and protein kinase C were critical in cardiomyocytes . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The tyrphostin AG 1478 , known to inhibit EGF receptor phosphorylation , also inhibited the angiotensin 2 and EGF induced activation of ERK , the phosphorylation of the EGF receptor , and the subsequent association of Shc and Grb 2 . ^^^ Nitric oxide did not affect either EGF receptor phosphorylation or Shc Grb 2 activation induced by either Ang 2 or EGF . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In contrast , the IGF 1 receptor chimera mediated more effective Shc phosphorylation , association of Shc with Grb 2 , and activation of mitogen activated protein kinase compared with the insulin receptor chimera . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Therefore , we studied Raf 1 activity , its potential activators protein kinase C ( PKC ) and Ras , and expression and associations of adapter proteins Shc , Grb 2 , and Sos during experimental gastric ulcer healing . ^^^ Our results demonstrate that gastric ulceration significantly increases Raf 1 kinase activity , Grb 2 and Ras protein , and Shc Grb 2 and Grb 2 Sos complex levels . ^^^ These findings indicate that Raf 1 activation during gastric ulcer healing is Ras mediated , involves Shc Grb 2 Sos , and is PKC independent . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
OA induced EGFR autophosphorylation triggered EGFR signaling pathway activation ( as assessed through coimmunoprecipitation of SH 2 proteins such as SHC , GRB 2 , and SHP 2 ) and subsequent p42 / p44 mitogen activated protein kinase ( as shown by the use of EGFR deficient B82L and EGFR transduced B82LK ( + ) cell lines ) . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
This phosphorylation is transformation associated , and the phosphorylated form of CaD is associated with a signaling complex consisting of Shc , Grb 2 , and Sos in transformed fibroblasts . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The truncated fragments were tyrosine phosphorylated under resting conditions , and associated with the signalling intermediates Shc and Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Accelerated mammary tumor development in mutant polyomavirus middle T transgenic mice expressing elevated levels of either the Shc or Grb 2 adapter protein . ^^^ The Grb 2 and Shc adapter proteins play critical roles in coupling activated growth factor receptors to several cellular signaling pathways . ^^^ To assess the role of these molecules in mammary epithelial development and tumorigenesis , we have generated transgenic mice which individually express the Grb 2 and Shc proteins in the mammary epithelium . ^^^ Although mammary epithelial cell specific expression of Grb 2 or Shc accelerated ductal morphogenesis , mammary tumors were rarely observed in these strains . ^^^ To explore the potential role of these adapter proteins in mammary tumorigenesis , mice coexpressing either Shc or Grb 2 and a mutant form of polyomavirus middle T ( PyV mT ) antigen in the mammary epithelium were generated . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Tyrosine phosphorylation of Shc in response to B cell Ag receptor ( BCR ) engagement creates binding sites for the Src homology 2 ( SH 2 ) domain of Grb 2 . ^^^ We found that both the SH 2 domain and phosphotyrosine binding ( PTB ) domain of Shc are important for BCR induced tyrosine phosphorylation of Shc and the subsequent binding of Grb 2 to Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Furthermore , a training induced co immunoprecipitation of IR with Shc 66 was detected , along with changes in in vivo Tyr phosphorylation of Shc and mitogen activated protein kinase , as well as accumulation of Shc 66 , Shc 52 , and Grb 2 in hippocampal synaptic membrane fractions following training . ^^^ These findings suggest that IR may participate in memory processing through activation of its receptor Tyr kinase activity , and they suggest possible engagement of Shc / Grb 2 / Ras / mitogen activated protein kinase cascades . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Neuregulin increases the association of the adaptor proteins Grb 2 and Shc with both ErbB 2 and ErbB 3 in C2C12 muscle cells . ^^^ Dephosphorylation of the tyrosine phosphorylated ErbB proteins abolished their association with both Grb 2 and Shc , suggesting a tyrosine phosphorylation dependent interaction . ^^^ Taken together , these data indicate that the interaction of ErbB receptors with Grb 2 alone is insufficient for neuregulin activated transcription , but that ErbB receptor signaling via Shc is necessary and important . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Glucose ( > 3 mM ) independently increased tyrosine phosphorylation mediated recruitment of growth factor bound protein 2 ( Grb 2 ) / murine sons of sevenless 1 protein ( mSOS ) and PI3 ' K to insulin receptor substrate ( IRS ) 1 and IRS 2 , as well as SH 2 containing protein ( Shc ) association with Grb2 / mSOS and downstream activation of mitogen activated protein kinase and 70 kDa S 6 kinase . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
EGF and NGF strongly activated tyrosine phosphorylation of Shc and caused association of Src homology collagen ( Shc ) with growth factor receptor bound protein 2 ( Grb 2 ) ; however , neither NE nor UTP caused substantial activation of the Shc / Grb2 pathway . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
By contrast , Shc and Grb 2 were inducibly associated with the EGFR in response to EGF stimulation of glioma cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
When stably expressed in K 562 cells , SHIP was found to be constitutively tyrosine phosphorylated and associated with endogenous Shc and Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
High affinity IgG receptor activation of Src family kinases is required for modulation of the Shc Grb 2 Sos complex and the downstream activation of the nicotinamide adenine dinucleotide phosphate ( reduced ) oxidase . ^^^ We used the U 937 cell line to examine the modulation of adaptor protein interactions ( Shc , Grb 2 , and Cbl ) after high affinity IgG receptor ( FcgammaRI ) cross linking , leading to the formation of the Grb 2 Sos complex , the activation of Ras , and the regulation of the respiratory burst . ^^^ Tyrosine phosphorylated Shc , mainly the p 52 isoform , was observed to transiently onload to the membrane Grb 2 Sos complex on FcgammaRI stimulation . ^^^ Cross linking of FcgammaRI induces the tyrosine phosphorylation of Cbl , which forms a complex with Grb 2 and Shc via the Cbl C terminus . ^^^ Kinetic experiments confirm that Cbl Grb 2 is relatively stable , whereas Grb 2 Sos , Grb 2 Shc , and Cbl Shc interactions are highly inducible . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Over expression of the wild type Ras protein or some of its regulatory components , such as Shc or Grb 2 , induces an amplification of PLD activation by PDGF challenge . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In addition to its catalytic activity on phosphatidylinositol substrates , it can serve as an adaptor protein in binding Shc and Grb 2 . ^^^ Erythropoietin ( EPO ) , the primary regulator of erythropoiesis , has been shown to activate the tyrosine phosphorylation of Shc , resulting in recruitment of Grb 2 . ^^^ EPO activates the tyrosine phosphorylation of Ship 1 , resulting in the interdependent recruitment of Shc and Grb 2 . ^^^ In addition , we have shown that EPO stimulates the formation of a ternary complex consisting of Ship 1 , Shc , and Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In cardiac fibroblasts AngII activated MAP kinases through a pathway including the Gbetagamma subunit of Gi protein , Src , Shc , Grb 2 , and Ras , while Gq and PKC activation was necessary in cardiac myocytes . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Evidence is also presented that Shp 2 does not appear to modulate the signal relay from EGF receptor to Ras through the Shc , Grb 2 , and Sos proteins . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Insulin stimulates rapid tyrosine phosphorylation of the protein Shc , which subsequently binds to Grb 2 , resulting in the activation of a complex mitogenic signaling network . ^^^ In this study , we examined the levels of Shc protein , its phosphorylation state and Shc Grb 2 association in liver , muscle and adipose tissue before and after insulin administration in three animal models of insulin resistance ( chronic dexamethasone treatment , 72 h starvation and aging ) . ^^^ Alterations in Shc phosphorylation correlated well with the level of Shc Grb 2 association . ^^^ These results indicate that Shc tyrosyl phosphorylation and Shc Grb 2 association are regulated in the different types of insulin resistance and that this regulation is apparently related to the animals ' plasma insulin levels . ^^^ The Shc Grb 2 association is directly related to the insulin induced tyrosyl phosphorylation of Shc . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
As previously reported , insulin induced Shc phosphorylation , Shc Grb 2 association , MAP kinase activation , and BrdU incorporation . ^^^ Okadaic acid also stimulated tyrosine phosphorylation of Shc and its subsequent association with Grb 2 in a time and dose dependent manner without affecting tyrosine phosphorylation of insulin receptor beta subunit and IRS . ^^^ Interestingly , preincubation of okadaic acid potentiated insulin stimulation of tyrosine phosphorylation of Shc ( 213 % of control ) , Shc Grb 2 association ( 150 % ) , MAP kinase activity ( 152 % ) , and BrdU incorporation ( 148 % ) . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Urea treatment also induced the tyrosine phosphorylation of Shc and the recruitment to Shc of Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Upstream events such as the Syk dependent phosphorylation of Shc , the engagement of Shc with the adapter protein , Grb 2 , and the activation of Ras itself are unaffected . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Expression of full length ATIC ALK cDNA in mouse fibroblasts revealed that the fusion protein ( a ) possesses constitutive tyrosine kinase activity ; ( b ) forms stable complexes with the signaling proteins Grb 2 and Shc ; ( c ) induces tyrosine phosphorylation of Shc ; and ( d ) provokes oncogenic transformation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Matrix induced tyrosine phosphorylation of an adaptor protein Shc with recruitment of Grb 2 was observed even when tubulogenesis was nearly completed at G 1 stage of the cell cycle in 2 3 weeks . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
H2O2 induced the phosphorylation of the EGF receptor and the formation of a receptor complex comprising Shc , Grb 2 , Sos , and the EGF receptor . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
This phosphoprotein complex includes Grb 2 , Shc , Sos , tyrosine phosphorylated form of caldesmon , and two , as yet , unidentified proteins . ^^^ The presence of Grb 2 , Shc , and Sos in this complex implicates Ras in ligand independent signaling by these oncogenic epidermal growth factor receptor mutants . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We analyzed the elements of the pathway that lead to this activation , and we observed that calmodulin antagonists completely block the initial Raf 1 activation without affecting the function of upstream elements , such as Ras , Grb 2 , Shc , and Trk . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Of note , IL 8 induced transient phosphorylation of the epidermal growth factor ( EGF ) receptor and its association with the adaptor molecules Shc and Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Shc is believed to be regulated by a change in subcellular localization from the cytosol to the plasma membrane , where it recruits Grb 2 / Sos complexes and hence permits juxtaposition of the guanine nucleotide exchange factor Sos to Ras , resulting in GDP / GTP exchange and Ras activation . ^^^ Membrane targeted Shc was phosphorylated on tyrosine residues and bound Grb 2 / Sos in the absence of TCR engagement . ^^^ Interestingly , a membrane targeted Shc mutant lacking both Grb 2 binding sites was not only incapable of signaling in the absence of TCR triggering , but transdominantly inhibited endogenous Shc , supporting a non redundant role for Shc in the activation of the Ras / MAP kinase pathway in T cells . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Grb 2 binding to TrkA is independent of Shc , FRS 2 , phospholipase Cgamma 1 , rAPS , and SH2B and is observed in in vitro binding assays , yeast two hybrid assays , and in co immunoprecipitation assays . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
CD 22 forms a quaternary complex with SHIP , Grb 2 , and Shc . ^^^ The adapter proteins Grb 2 and Shc were found to interact with distinct and specific regions of the CD 22 cytoplasmic domain . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Involvement of proline rich tyrosine kinase 2 in platelet activation : tyrosine phosphorylation mostly dependent on alphaIIbbeta 3 integrin and protein kinase C , translocation to the cytoskeleton and association with Shc through Grb 2 . ^^^ In immunoprecipitation studies , Pyk 2 , as well as FAK , seemed to associate with Shc through Grb 2 . ^^^ With the use of glutathione S transferase fusion proteins containing Shc SH 2 , Grb 2 SH2 , and Grb 2 N terminal and C terminal SH 3 domains , it was implied that the proline rich region of Pyk 2 ( and FAK ) binds to the N terminal SH 3 domain of Grb 2 and that the phosphotyrosine residue of Shc binds to the SH 2 domain of Grb 2 . ^^^ Furthermore , Pyk 2 , as well as FAK , might have one or more important roles in post aggregation tyrosine phosphorylation events , in association with the cytoskeleton and through interaction with adapter proteins including Grb 2 and Shc . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In cardiac fibroblasts , angiotensin 2 activated ERK via the G ( beta ) gamma subunit of Gi , Src , Shc , Grb 2 , and Ras , whereas Gq and protein kinase C were critical in cardiomyocytes . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In contrast , insulin induced association of Shc and Grb 2 was not inhibited . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The enhanced activation of EGFR by the tethered form of TGFalpha was reflected by higher activation of Grb 2 , SHC and Erk downstream mediators of EGF receptor signaling . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Coimmunoprecipitation studies demonstrated that both EGF and Cpd 5 induced tyrosine phosphorylation of EGFR was associated with increased amounts of adapter proteins Shc and Grb 2 , and the Ras GTP GDP exchange protein Sos , indicating the formation of functional EGFR complexes . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
However , we did not detect interactions with Grb 2 , SHC , or phospholipase C gamma . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Under these conditions , cAMP pretreatment significantly increased binding of Grb 2 ( growth factor receptor bound protein 2 ) to Shc in response to IGF 1 , and activation of MAP kinase ( mitogen activated protein kinase ) induced by IGF 1 was also enhanced by cAMP . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We found that the signaling pathway involves the activation of epidermal growth factor receptor ( EGFR ) kinase , activation of the adaptor proteins Shc and Grb 2 , and the small G protein Ras . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In addition , there is an increased association between the Grb 2 protein and Shc proteins upon PRL stimulation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
SP induced formation of an activated EGFR complex containing the adapter proteins SHC and Grb 2 , but not c Src . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
TPA treatment of MCF 7 cells caused an increased association of Shc with Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Natural analogues ( D , C 2 , and 7 ) of actinomycin inhibit Grb 2 SH2 domain binding with phosphopeptide derived from Shc in vitro and in intracellular system . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Furthermore , a pTyr 317 Shc phosphopeptide selectively recognized Grb 2 , Sos 1 , SHIP , and the p 85 subunit of phosphatidylinositol 3 ' kinase from mast cells , as characterized by mass spectrometry . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Stimulation with SCF + ET 1 induced a more rapid and stronger tyrosyl phosphorylation of proteins corresponding to p 52 and p 66 Shc than did stimulation with SCF only , and this was accompanied by a stronger association of tyrosine phosphorylated Shc with Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
There was little or no tyrosine phosphorylation of Shc or association of Grb 2 with Shc or IRS 1 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Grb 2 bridges receptors to tyrosine kinase substrates such as SHC and SOS , which in turn facilitate the activation of downstream signaling pathways , including Ras and mitogen activated protein kinase ( MAPK ) . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In addition , independent of PKC 12 ( S ) HETE increases tyrosine phosphorylation of Shc , and Grb 2 , stimulates association between Shc and Src , and increases the activity of Ras , via Src family kinases . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Mechanism of mitogenic effect of fluoride on fetal rat osteoblastic cells : evidence for Shc , Grb 2 and P CREB dependent pathways . ^^^ It suggests that tyrosine kinase mediated mitogenic signaling involves a series of protein protein interactions between tyrosine phosphorylated receptors , Shc and Grb 2 , resulting in an AlFx induced mitogenic effect . ^^^ The results indicate that AlFx dose dependently enhances the tyrosine phosphorylation of the adaptor molecule Shc ( p 52 ) and its association with Grb 2 in the tyrosine kinase mediated pathway . ^^^ Taken together , the results suggest that adaptor proteins , including Shc and Grb 2 of the protein tyrosine kinase cascade are implicated in fluoride induced mitogenic activity of fetal rat calvarial osteoblastic cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
To further evaluate the mechanism by which SFFV activates the Raf 1 / MAPK pathway , we investigated the effects of SFFV on upstream components of this pathway , and our results indicate that SFFV activates Shc and Grb 2 and that this leads to Ras activation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The components of this signaling complex include the signal adapter proteins Shc , Grb 2 , and Nck , and tyrosine phosphorylated forms of p 21 activated kinase ( Pak ) , caldesmon , and myosin light chain kinase . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Analysis of these cells indicates that FAK is not necessary for efficient tyrosine phosphorylation of Shc , association of Shc with Grb 2 , and activation of ERK in response to matrix adhesion . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
TRH induced EGF receptor phosphorylation was found to lead to the recruitment of the adapter proteins Grb 2 and Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Here , we show that the protooncoprotein Shc , which promotes Ras activation by recruiting the Grb 2 Sos complex in response to stimulation of cytokine stimulation , also signals to the PI 3K / Akt pathway . ^^^ Mutation of the three tyrosyl phosphorylation sites of Shc , which bind Grb 2 , blocks the ability of the Shc chimera to evoke Gab 2 tyrosyl phosphorylation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Moreover , we demonstrate that addition of both linker for activation of T cells ( LAT ) and Grb 2 related adaptor downstream of Shc ( Gads ) to SLP 76 allow SLP 76 to be recruited into GEMs , whereby the BCR function is reconstituted . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Ligand stimulation of neuronal cells induced the assembly of a large protein complex containing c Ret , Grb 2 , and tyrosine phosphorylated forms of Shc , p 85 ( PI3K ) , the adaptor Gab 2 , and the protein tyrosine phosphatase SHP 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Ret oncogene signal transduction via a IRS 2 / PI 3 kinase / PKB and a SHC / Grb 2 dependent pathway : possible implication for transforming activity in NIH3T3 cells . ^^^ Moreover , Ret 9bp induces phosphorylation of SHC resulting in growth factor receptor binding protein 2 ( Grb 2 ) binding and activation of the mitogen activating protein ( MAP ) kinase pathway . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In response to GDNF stimulation , SHC bound to GAB 1 and GRB 2 adaptor proteins as well as RET , and SHC and GAB 1 were highly phosphorylated on tyrosine . ^^^ The complex formation consisting of SHC , GAB 1 and GRB 2 was almost abolished by replacement of tyrosine 1062 in RET with phenylalanine . ^^^ Tyrosine phosphorylated GAB 1 was also associated with p 85 subunit of PI 3 K , resulting in PI 3 K and AKT activation , whereas SHC GRB 2 SOS complex was responsible for the RAS / ERK signaling pathway . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Grb 2 protein is comprised of one SH 2 surrounded by two SH 3 domains and interacts by means of its Src homology ( SH 2 ) domain with phosphotyrosine residues of target proteins such as the epidermal growth factor ( EGF ) receptor or the Shc adaptor . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The Grb 2 adaptor was recruited by the upstream Src homology 2 / alpha collagen related ( Shc ) effector , as the SH 2 Shc domain prevented the GVBD and the ERK 2 phosphorylation induced by FGF 1 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
RET dimerization and its complex formation with Shc and Grb 2 adaptor proteins were detected in tumor tissues . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In OVCA 433 human ovarian carcinoma cells , ET 1 caused phosphorylation of the epidermal growth factor receptor ( EGF R ) that was accompanied by phosphorylation of Shc and its recruitment complexed with Grb 2 . ^^^ Specific inhibition of EGF R kinase activity by tyrphostin AG 1478 prevented ET 1 induced transactivation of the EGF R , as well as Shc phosphorylation and recruitment with Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In the present study , we demonstrate that oncostatin M ( OSM ) , but not IL 6 or leukemia inhibitory factor , induces tyrosine phosphorylation of the Shc isoforms p 52 and p 66 and their association with Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
They interact with tyrosine phosphorylated Shp 2 , p 85 , Grb 2 , and Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Signaling from PI3Kgamma to MAPK appears to require in our murine cellular system a tyrosine kinase ( still not characterized ) , Shc , Grb 2 , Sos , Ras and Raf . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In the present study , we investigated if these results were related to changes in the mobilization of intracellular calcium , activation of phospholipase D ( PLD ) or amounts of GPIIIa and the intracellular tyrosine kinases Fak , Syk , Grb 2 , Shc and rhoA . ^^^ Levels of Fak , Syk , Shc , Grb 2 and rhoA appeared equal in patients and controls . ^^^ Moreover , no apparent differences in the intracellular amounts of Fak , Syk Shc , Grb 2 and rhoA could be detected between PV and control platelets . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Transient expression of Vav in 293T and NIH 3T3 cells demonstrated that ligand stimulation of several RPTKs ( epidermal growth factor receptor [ EGFR ] , Ros , insulin receptor [ IR ] , and insulin like growth factor 1 receptor [ IGFR ] ) led to tyrosine phosphorylation of Vav 3 and its association with the receptors as well as their downstream signaling molecules , including Shc , Grb 2 , phospholipase C ( PLC gamma ) , and phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The multisubstrate docking site mediates the binding of several adapter proteins such as Grb 2 , SHC , Crk / CRKL , and the large adapter protein Gab 1 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
ANG 2 ( 100 nM ) promoted the formation of a complex between PYK 2 and the ERK1 / 2 regulators Shc and Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
These results show that , in addition to Shc and Grb 2 , a PI3K dependent pathway involving Gab 1 and SHP 2 is essential for Ras activation under EGF stimulation . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Grb 2 and Shc adapter proteins play distinct roles in Neu ( ErbB 2 ) induced mammary tumorigenesis : implications for human breast cancer . ^^^ The transforming potential of two of these mutants correlates with their capacity to recruit Grb 2 directly to Y 1144 ( YB ) or indirectly through Shc to Y 1227 ( YD ) . ^^^ To further address the significance of these ErbB 2 coupled signaling molecules in induction of mammary cancers , transgenic mice expressing mutant Neu receptors lacking the known autophosphorylation sites ( NYPD ) or those coupled directly to either Grb 2 ( YB ) or Shc ( YD ) adapter molecules were derived . ^^^ These observations argue that Grb 2 and Shc play important and distinct roles in ErbB 2 / Neu induced mammary tumorigenesis and metastasis . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In this report , we identify this 100 kDa protein as the recently cloned scaffolding protein Gab 2 , and we demonstrate that Gab 2 associates with several molecules involved in M CSF signaling , including Grb 2 , SHP 2 , the p 85 subunit of phosphatidylinositol 3 ' kinase , SHIP , and SHC . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
TEL JAK 2 , in addition to activating Stat 5 , associates with Shc and Grb 2 and induces activation of Erk 2 , and expression of Socs 1 inhibits engagement of each of these signaling molecules . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
On the contrary , the significant decrease of Shc phosphorylation , Grb 2 recruitment and the reduced phosphorylation level of Akt Thr 308 and Akt substrates FKHR and Bad detected in transgenic glands show that activation of the Shc and the Akt pathways require intact cell ECM interactions . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In this study , we show that upon thrombopoietin ( Tpo ) stimulation the two adapter proteins Gab 1 and Gab 2 are strongly tyrosine phosphorylated and associated with Shc , SHP 2 , PI 3 kinase and Grb 2 in mpl expressing UT 7 cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
LPC stimulated the association of Shc with PYK 2 , Shc tyrosine phosphorylation , and Grb 2 binding to Shc and induced Ras activation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Our results indicate that while there are measurable differences in the abilities of the two mutant receptors to stimulate [ ( 3 ) H ] thymidine incorporation between 20 and 24 h after addition of EGF , these differences can not be correlated with significant differences in EGF stimulated tyrosine phosphorylation of mutant EGF receptor and endogenous ErbB 2 , the extent of receptor internalization , EGF stimulated ion uptake , stimulation of SHC activity , or receptor association with Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Grb 2 can bind EGFR directly or through another SH 2 containing protein , Shc . ^^^ To analyse the spatial and temporal regulation of EGFR interactions with SH 2 domains in living cells , we have combined imaging microscopy with a modified method of measuring fluorescence resonance energy transfer ( FRET ) on a pixel by pixel basis using EGFR fused to cyan fluorescent protein ( CFP ) in pair with Grb 2 or Shc fused to yellow fluorescent protein ( YFP ) . ^^^ Stimulation by EGF resulted in the recruitment of Grb 2 YFP and YFP Shc to cellular compartments that contained EGFR CFP , and a large increase in the FRET signal . ^^^ In particular , FRET measurements indicated that activated EGFR CFP interacted with YFP Shc and Grb 2 YFP in membrane ruffles and endosomes . ^^^ Moreover , in contrast with previous biochemical studies , FRET experiments show that a large pool of Grb 2 and Shc is associated with EGFRs for a prolonged period after EGF stimulation . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We show that a substantial fraction of tyrosine phosphorylated epidermal growth factor receptor ( EGFR ) and Shc , Grb 2 and Cbl after internalization relocates from early endosomes to compartments which are negative for the early endosomes , recycling vesicle markers EEA 1 and transferrin in EGF stimulated cells . ^^^ Co immunoprecipitations showed EGFR in complex with both Shc , Grb 2 and Cbl . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Grb 2 and Shc ) are also degraded in an EGF induced Cbl b dependent fashion . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
IGF 1 induced tyrosine phosphorylation of Shc and its subsequent association with Grb 2 were increased in WT Shc cells , whereas they were decreased in 3F Shc cells compared with those in parental L 6 cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Also GST Grb 2 SH2 proteins exclusively bound to the p 46 ( Shc ) , p 52 ( Shc ) , and p 66 ( Shc ) are important adaptors of the Ras pathway in HepG 2 cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
CD 2 crosslinking markedly induced tyrosine phosphorylation of Cbl associated with Grb 2 or CrkL , Shc and LAT , compared with IL 2 stimulation . ^^^ However , costimulation of IL 2 with CD 2 crosslinking remarkably enhanced associations of Grb 2 Shc and CrkL Cbl , compared to IL 2 stimulation or CD 2 crosslinking alone . ^^^ In vitro binding studies using GST fusion proteins revealed that interactions of Grb 2 Shc and CrkL Cbl were mediated through each SH 2 domain in tyrosine phosphorylation dependent manner . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Second , disruption of the interaction of the insulin receptor with PLC gamma 1 by microinjection of SH 2 domains derived from PLC gamma 1 or Grb 2 but not Shc similarly blocks insulin induced DNA synthesis . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Immunoblotting indicated the presence of Shc , Grb 2 , Ras ( p 21 ) , Raf and ERK 1 and 2 ( ERK1 / 2 ) in spermatozoa . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The transforming potential of at least two of these autophosphorylation sites ( Tyr ( 1144 ) and Tyr ( 1226 / 1227 ) ) has been further correlated with their ability to associate with Grb 2 and Shc adapter proteins , respectively . ^^^ The results showed that Grb 2 recruitment to site 1144 is absolutely required for transforming signal from this autophosphorylation site , whereas association of Shc mediated transformation is dependent on conservation of the NPXY motif spanning Tyr ( 1227 ) . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In addition to the EGF receptor , PI3K C2beta ( 2 298 ) also isolated both Shc and Grb 2 from A 431 cell lysates . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Binding of EGF and PDGF to the receptors activates receptor tyrosine kinase and rapid association of adapter proteins Shc and Grb 2 , and evokes the Ras / MAP kinase cascade . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Thus , by binding to Shc , CEACAM 1 sequesters this major coupler of Grb 2 to the insulin receptor and down regulates the Ras / MAP kinase mitogenesis pathway . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We examined the classical signal pathway in which SHC is phosphorylated and binds to SOS and GRB 2 to activate Ras , Raf , and MAP kinase . ^^^ With 5 20 min of exposure , estradiol caused binding of SHC to the estrogen receptor , phosphorylation of SHC , binding of GRB 2 to SOS , and activation of MAP kinase . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
UV induced neither relocalisation of Shc and Grb 2 nor activation of Raf , but activation of MEK and MAPK was observed . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
However , SHC expression and SHC tyrosine phosphorylation and its association with Grb 2 were unaltered in response to insulin in IGF IR deficient brown adipocytes . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Treatment with 17 AAG decreased NPM ALK expression and phosphorylation , thus impairing its association with phospholipase C gamma , Src homology 2 domain containing protein ( Shc ) , growth factor receptor bound protein 2 ( Grb 2 ) , and insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Use of signal specific receptor tyrosine kinase oncoproteins reveals that pathways downstream from Grb 2 or Shc are sufficient for cell transformation and metastasis . ^^^ We have generated variant forms of the Tpr Met oncoprotein with the ability to bind individually to the p 85 subunit of PI3 ' K , PLCgamma , or to the Grb 2 or Shc adaptor proteins . ^^^ Variants that recruit the Shc or Grb 2 adaptor proteins generated foci of morphologically transformed fibroblast cells and induced anchorage independent growth , scattering of epithelial cells and experimental metastasis . ^^^ Using this unique RTK oncoprotein model , we have established that Grb 2 or Shc dependent signaling pathways are sufficient for cell transformation and metastatic spread . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Surprisingly , EGF and TGF alpha induced full activation of MAPK in duration and intensity and stimulated association of the EGFR with Shc and Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In addition , in common with NPM ALK , the TFG ALK proteins formed stable complexes with the signaling proteins Grb 2 , Shc , and PLC gamma . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
However , insulin induced tyrosine phosphorylation of the insulin receptor and SHC , and the association of SHC / growth factor receptor binding protein 2 ( GRB 2 ) decreased significantly from d 1 to wk 60 of life in both types of tissues . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In thrombin activated platelets , the Grb 2 SH2 domain formed an association with the beta 3 subunit of the alphaIIb beta 3 integrin ( GPIIb IIIa ) , Shc , Syk , Src and SHP 1 ( SH 2 containing phosphotyrosine phosphatase 1 ) , whereas these associations did not occur after the engagement of the receptor for the Fc domain of IgG ( FcgammaRIIa ) or in resting platelets . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Moreover , the GH induced association of IRS 1 / phosphatidylinositol 3 kinase , IRS 1 / growth factor receptor bound 2 ( Grb 2 ) , and Shc / Grb2 are increased in diabetic rats as well . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
TEL JAK 2 expression in Ba / F3 cells results in constitutive association and tyrosine phosphorylation of Shc and Ship 1 and , consequently , recruitment of Grb 2 to TEL JAK 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In turn , Shc bound Grb 2 and Sos which resulted in the activation of MAP kinase . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
To directly explore the role of Shc we used the ShcY317F mutant , which carries the mutation of a tyrosine residue involved in Grb 2 recruitment . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Although it interacts with the ErbB 2 C terminus through the PDZ domain , Erbin has no effect on ErbB 2 tyrosine phosphorylation or binding to the adaptor proteins Shc and Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Ligand mediated activation allows EphA 2 to form a molecular complex with the SHC and GRB 2 adaptor proteins . ^^^ We also show that the interaction of EphA 2 with GRB 2 is indirect and mediated by SHC and that this complex is necessary for EphA 2 mediated activation of ERK kinases . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
This form of alpha 6 integrin coimmunoprecipitated with both the signaling adaptor molecule Shc and its downstream effector Grb 2 , suggesting that , in lens fiber cells , uncleaved alpha 6 integrin was associated with a Shc mediated signaling complex . ^^^ Its high association with Shc and Grb 2 in the differentiating cortical fiber cell zone indicates that alpha 6 integrin may provide a cell survival signal in the presence of the apoptotic like processes that are initiated in this region of the embryonic lens to clear the lens cells of their organelles . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
RasGAP and Shc were also found to associate with GRB 2 in LA significantly more in the conditioned animals . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
With regard to the large effect on MAPK phosphorylation , we found that PTP1B overexpression led to the impaired phosphorylation of both IRS 1 and Shc , resulting in a decrease in their association with Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In addition , LH induced IRS 1 / phosphoinositol 3 kinase and Shc / growth factor receptor binding protein 2 ( Grb 2 ) associations and downstream AKT ( protein kinase B , homologous to 5 AKT ) serine phosphorylation and ERK tyrosine phosphorylation , respectively . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Combined cell lysates were affinity purified over the SH 2 domain of the adapter protein Grb 2 ( GST SH 2 fusion protein ) that specifically binds phosphorylated EGFR and Src homologous and collagen ( Shc ) protein . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Immunoprecipitation / Western blot studies revealed that BK stimulated tyrosine phosphorylation of EGFR , its association with an adapter molecule Grb 2 , and complex formation between Grb 2 and the adapter protein Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The PER mutant with all five autophosphorylation sites mutated to phenylalanine ( 5YF ) was equivalently capable of interacting with several important signaling molecules , including Shc , Grb 2 , Gab 1 , phospholipase Cgamma , and Cbl . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Along with ErbB 4 , adaptor proteins Grb 2 and Shc were translocated to lipid rafts by NRG stimulation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The tyrosine phosphorylated EGFR was immunoprecipitated together with GRB 2 and tyrosine phosphorylated Shc , indicating that transactivated EGFR is able to generate downstream signals . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Gab 1 and Gab 2 are scaffolding proteins acting downstream of cell surface receptors and interact with a variety of cytoplasmic signaling proteins such as Grb 2 , Shp 2 , phosphatidylinositol 3 kinase , Shc , and Crk . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Conversely , TGF beta 1 did not alter IGF 1 stimulated IRS 1 associated phosphatidylinositol 3 kinase activity , IGF 1 induced tyrosine phosphorylation of Shc , and its binding to Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
When crossed with mice expressing activated forms of the Neu receptor tyrosine kinase that selectively couple to the Grb 2 or Shc signaling pathways the activated type 1 receptor increased the latency of mammary tumor formation but also enhanced the frequency of extravascular lung metastasis . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
However , even at concentrations of 0 . 1 to 1000 microM , no significant inhibitions were observed against other SH 2 domains binding such as the growth factor receptor binding protein 2 ( Grb 2 ) SH 2 domain to phosphopeptide of Shc and phospholipase Cgamma 1 ( PLCgamma 1 ) SH 2 domain to translational elongation factor 1alpha ( EF1alpha ) C terminal . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Morphine caused serine phosphorylation of the IR and impaired the formation of the signaling complex among the IR , Shc , and Grb 2 . ^^^ These results suggest that morphine attenuates IR signaling to Akt by disrupting the IRS 1 p 85 interaction but inhibits signaling to ERK by disruption of the complex among the IR , Shc , and Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
These growth factors , most notably EGF , trigger cell proliferation via signal transduction pathways involving EGF R , adapter proteins ( Grb 2 , Shc and Sos ) , Ras , Raf 1 and MAP ( Erk1 / Erk2 ) kinases , which , after translocation to nuclei , activate transcription factors and cell proliferation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Specificity of insulin like growth factor 1 and insulin on Shc phosphorylation and Grb 2 recruitment in caveolae . ^^^ In R IGF IRWT cells , IGF 1 causes Fyn enrichment in the caveolae with a time course consistent with Shc phosphorylation and Grb 2 recruitment in these regions . ^^^ Here we show that insulin also induces Shc phosphorylation and Grb 2 recruitment to caveolae , but with a significantly different time course compared with IGF 1 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
To further define the events linking the membrane distal tyrosine and JNK activation , the Src homology 2 domains of Shc , Grb 2 , and 3BP2 were shown to bind the full length GCSF R and a phosphopeptide encompassing the membrane distal tyrosine . ^^^ When binding to variant phosphopeptides based on this membrane distal tyrosine was tested , altering the amino acids immediately following the phosphotyrosine could selectively abolish the interaction with Shc or Grb 2 , or the binding to both Grb 2 and 3BP2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
By using this system , we showed that endosomal activation of PDGFR recruits various signaling proteins including Grb 2 , SHC , phospholipase C gamma 1 , and the p85alpha subunit of phosphatidylinositol 3 kinase into endosomes and forms signaling complexes with PDGFR . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Although phosphorylation of Gab 2 was similar in WT and mutant cell lines , phosphorylation of Shc on Tyr ( 313 ) in response to IGF 1 was decreased in cells expressing the mutant receptor , as was recruitment of Grb 2 and Ship to Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
To define the role of RTK dependent signals in various oncogenic processes , we have previously engineered RTK oncoproteins that recruit either the Shc or Grb 2 adaptor proteins . ^^^ Although these RTK oncoproteins transform cells with similar efficiencies , fibroblasts expressing the Shc binding RTK oncoproteins induced tumors with short latency ( approximately 7 days ) , whereas cells expressing the Grb 2 binding RTK oncoproteins induced tumors with delayed latency ( approximately 24 days ) . ^^^ The importance of Shc recruitment to RTKs for the induction of VEGF was further demonstrated by using mutants of the Neu / ErbB2 RTK , where the Shc , but not Grb 2 , binding mutant induced VEGF . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Additionally , GH induced further accumulation of GHR , Grb 2 , and SHC proteins in the CM fraction . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Here we report on the structural dynamic effects upon interaction of a phosphopeptide ligand derived from the recognition sequence of the Shc adaptor protein with ( 1 ) the isolated SH 2 domain of Grb 2 ( Grb 2 SH2 ) and ( 2 ) the full length Grb 2 protein . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In contrast , control studies in ligand stimulated A 431 human cancer cells revealed an additional phosphorylated subset of promitogenic phosphoproteins ( Grb 2 , Shc , Jnk 2 , phospholipase C gamma , and phosphatidylinositol 3 ' kinase ) . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Thus , SHIP competes son of sevenless ( SOS ) away from Shc Grb 2 . ^^^ In summary , 1 ) SHIP WT and SHIPDeltaIP expression inhibit insulin and PDGF stimulated Ras , MAPK kinase , and MAPK activities ; 2 ) SHIP associates with tyrosine phosphorylated Shc , and the proline rich sequences in SHIP associate with Grb 2 and titrate out SOS to form Shc * Grb2 * SHIP complexes ; and 3 ) dissociation of SOS from the Shc * Grb2 complex inhibits Ras GTP loading , leading to decreased signaling through the MAPK pathway . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Epidermal growth factor receptor ( EGFR ) tyrosine phosphorylation and recruitment of its adaptor proteins , Shc and Grb 2 , to EGFR were detected by immunoprecipitation and Western blot analysis . ^^^ After arsenical treatment , Shc immunoprecipitates contained coprecipitated EGFR and Grb 2 , suggesting that both arsenicals induce the assembly of EGFR Shc Grb 2 complexes . ^^^ CONCLUSIONS : Our data indicate that both arsenite and arsenate activate the EGFR Shc Grb 2 MEK1 / 2 ERK1 / 2 signalling cascade in NHEK . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Incubation of 1 LN cells with alpha2M * induced Grb 2 , shc , sos and Raf 1 expression , as well as phosphorylation of MEK 1 / 2 , ERK 1 / 2 , p 38 MAPK and JNK . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The results show that IGF 1 induced Shc phosphorylation and its subsequent binding to Grb 2 is required for sustained phosphorylation of MAPK and increased cell proliferation in SMCs . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In addition , similar results for Cav3 . 1 activation were also shown in the case of Sos 1 , Grb 2 , and Shc , which means that Cav3 . 1 activation triggers p 21 ( ras ) and that this signal is transferred to ERK by Sos 1 , Grb 2 , and Shc . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Shc adapter proteins are thought to regulate cellular proliferation , differentiation and apoptosis by activating the SOS Grb 2 RAS MAPK signaling cascade . ^^^ We then recapitulated phosphorylation dependent Shc Grb 2 complex formation in Saccharomyces cerevisiae . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
To conduce these activities , the cytoplasmic C terminal region of this receptor acts as a docking site for multiple protein substrates , including Grb 2 , Gab 1 , STAT 3 , Shc , SHIP 1 and Src . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Shc and Grb 2 proteins are important molecules in Ras signaling pathways leading to cellular differentiation and proliferation , which require dramatic morphological changes . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Consistent with the suppression , NAC inhibited NGF induced activation of TrkA , formation of receptor complexes comprising TrkA , Shc , Grb 2 , and Sos , and activation of phospholipase Cgamma and phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In addition to interactions with multiple signaling adaptors Grb 2 , SHC , SCK , and NSP 2 , EGF receptors in HN 5 cells were shown to form direct or indirect physical interactions with additional kinases including ACK 1 , focal adhesion kinase ( FAK ) , Pyk 2 , Yes , EphA 2 , and EphB 4 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Prolidase activity and collagen biosynthesis are supposed to be regulated by beta ( 1 ) integrins , which initiate a signaling pathway in which several kinases and intracellular proteins are involved , including focal adhesion kinase pp 125 ( FAK ) ( FAK ) , Src , Shc , growth factor receptor bound protein 2 ( Grb 2 ) , son of sevenless protein ( SOS ) , Ras , Raf and mitogen activated protein kinases ( MAPK ) , extracellular signal regulated kinase 1 ( ERK ( 1 ) ) and kinase 2 ( ERK ( 2 ) ) . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
A constitutive complex of Grb 2 and Cbl could be recruited to both receptor isoforms via docking of Shc to phosphorylated Tyr 1062 in RET . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
To elucidate the downstream signaling in the PC9 / ZD cellular machinery , complex formation between EGFR and its adaptor proteins GRB 2 , SOS , and Shc was examined . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Analysis of detergent resistant membrane fractions revealed that the EGF dependent association of endocytic proteins with rafts is as efficient as that of signaling effector molecules , such as Grb 2 or Shc . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Dramatic inhibition of interaction between docking protein Shc and GST Grb 2 was observed at late stages of cell induction ( 48 72 h ) while binding of pY containing proteins during this period did not differ significantly in control and differentiated cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The intracellular pathways used by neurotrophins share many common protein substrates that are used by other receptor tyrosine kinases ( RTK ) , such as Shc , Grb 2 , FRS 2 , and phospholipase C gamma . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Oncogenic Met receptor induces cell cycle progression in Xenopus oocytes independent of direct Grb 2 and Shc binding or Mos synthesis , but requires phosphatidylinositol 3 kinase and Raf signaling . ^^^ We show that cell cycle progression and activation of MAPK and JNK mediated by the oncogenic Met receptor , Tpr Met , are dependent on its kinase activity and the presence of the twin phosphotyrosine ( Y 482 & Y 489 ) residues in its C terminus , but that the recruitment of Grb 2 and Shc adaptor proteins is dispensable , implicating other signaling molecules . ^^^ However , using Met receptor oncoproteins engineered to recruit specific signaling proteins , we demonstrate that recruitment of Grb 2 or Shc adaptor proteins is sufficient to induce cell cycle progression and activation of MAPK and JNK , while the binding of phospholipase Cgamma or phosphatidylinositol 3 kinase alone fails to elicit these responses . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We also found that the receptor proximal events accompanying Tat induced Ras activation are mediated by tyrosine phosphorylation of Shc and recruitment of Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Using variant forms of Tpr Met that are engineered to recruit a specific signaling molecule of choice , we demonstrate that the sole recruitment of either the Grb 2 or the Shc adaptor protein is sufficient to induce ectopic structures and anterior reduction , while the recruitment of PI 3Kinase ( PI 3K ) is necessary but not sufficient for this effect . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Nucleotide exchange stimulation by PE is prevented by PKC ( protein kinase C ) inhibition but not by EGFR [ EGF ( epidermal growth factor ) receptor ] blockade , despite the fact that EGFR inhibition aborts basal and PE induced Shc ( Src homology and collagen homology ) phosphorylation and Shc Grb 2 ( growth factor receptor bound protein 2 ) association . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
HGF stimulated Gab 1 association with c Met , Grb 2 , SHP 2 , PI3K , Shc , Crk isoforms and CrkL , but not with PLCgamma 1 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The interaction between p85alpha SH 3 and BCR / ABL may be intermediated by proteins such as c Cbl , Shc , Grb 2 , and / or Gab 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The model includes EGF , EGFR , the adapter proteins Grb 2 and Shc , and the guanine nucleotide exchange factor Sos , which is activated through EGF induced formation of EGFR Grb 2 Sos and EGFR Shc Grb 2 Sos assemblies at the plasma membrane . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NEU 3 markedly enhanced tyrosine phosphorylation of integrin beta 4 with recruitment of Shc and Grb 2 only on laminin 5 , and NEU 3 was co immunoprecipitated by an anti ( integrin beta 4 ) antibody , suggesting that association of NEU 3 with integrin beta 4 might facilitate promotion of the integrin derived signalling on laminin 5 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The adaptor protein Gab 2 coordinates the assembly of the IL 3 signalsome comprising Gab 2 , Grb 2 , Shc , SHP 2 and PI3K . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
ShcA and Grb 2 mediate polyoma middle T antigen induced endothelial transformation and Gab 1 tyrosine phosphorylation . ^^^ Requirement for a ShcA PTB domain binding site was suppressed by replacing this motif in PymT with YXN sequences , which bind the Grb 2 SH2 domain upon phosphorylation . ^^^ Surprisingly , PymT recruitment of ShcA and Grb 2 correlated with PI3K activation . ^^^ PymT mimics activated receptor tyrosine kinases by forming a ShcA Grb 2 Gab1 complex , thus inducing Gab 1 tyrosine phosphorylation , which itself is associated with PI3K . ^^^ Therefore , PymT activation of ShcA Grb 2 signaling is critical for endothelial transformation , and PymT can stimulate Grb 2 signaling to both the MAP kinase and PI3K pathways . . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
ShcA and Grb 2 are crucial components in signalling by most tyrosine kinase associated receptors . ^^^ How ever , it is not clear whether Grb 2 bound directly to the receptor is equivalent to Grb 2 associated via ShcA . ^^^ The two known Grb 2 binding sites from murine ShcA , 313Y and 239 / 240YY , could functionally replace the MT ShcA interacting region in transformation assays using Rat 2 fibroblasts . ^^^ Two standard Grb 2 interacting sequences , either from the EGF receptor or the ShcA 313Y region , could not replace the requirement for ShcA binding to MT , indicating an enhanced role for the ShcA 239 / 240YY motif . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
The expression of beta ( 1 ) integrin receptor , as well as Sos 1 and phosphorylated MAPK , ERK ( 1 ) and ERK ( 2 ) but not FAK , Shc , and Grb 2 was significantly decreased in cells incubated for 24h with 20 microM AB 4 compared to the control , not treated cells , whereas in the same conditions melphalan did not evoke any changes in expression of all these signaling proteins , as shown by Western immunoblot analysis . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In this report , we demonstrate that class 2 phosphoinositide 3 kinase C2beta ( PI3KC2beta ) associates with the Eps8 / Abi1 / Sos1 complex and is recruited to the EGF receptor as part of a multiprotein signaling complex also involving Shc and Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Activation of GPCRs sometimes results in a phenomenon known as `` transactivation ' ' of RTKs , which leads to the recruitment of scaffold proteins , such as Shc , Grb 2 , and Sos in addition to mitogen activated protein kinase activation . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Phosphorylation of human ShcA at Tyr 317 within its central ( CH 1 ) region induces binding to the Grb 2 SH2 domain and is thereby implicated in activation of the Ras pathway . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
These phenomena were peculiar to ShcA , since Grb 2 adaptor protein remained expressed at constant level throughout development . ^^^ The embryonically expressed ShcA proteins were functionally active , since p 52 ( ShcA ) became phosphorylated on tyrosine and associated with Grb 2 following intraventricular injection of epidermal growth factor in the embryonic brain . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Tyrosine phosphorylation stimulates PI3K and PLCgamma 1 enzymatic activity , and on ShcA creates binding sites for Grb 2 with its associated Sos 1 and Gab 1 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Irradiation of keratinocytes increases the phosphorylation of EGFR on tyrosine residues Y 845 , Y 992 , Y 1045 , Y 1068 , Y 1086 , Y 1148 , and Y 1173 above the basal levels and leads to the increased recruitment of the adaptor proteins Grb 2 and ShcA and of a p 55 form of the regulatory subunit of the phosphatidylinositide 3 kinase to the UVB activated EGFR . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Grb 2 also is involved in complexes with ShcA and tyrosine phosphorylated CTFs , and in AD brain the interaction between Grb 2 ShcA and CTFs is enhanced . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Receptor tyrosine kinases ( RTKs ) recruit adaptors , such as Grb 2 and ShcA , that activate signaling pathways involved in growth and survival , whereas death receptors bind adaptors , such as Fadd , that promote apoptosis . ^^^ To test the ability of interaction domains to create new signaling pathways , we have fused the phosphotyrosine recognition domains of Grb 2 ( Scr homology 2 domain ) or ShcA ( phosphotyrosine binding domain ) to the death effector domain of Fadd . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
In this present study using the small interfering RNA technique , we have found that ShcA adapter proteins play a rather active role in CSR induced Erk activation , contrary to their mostly redundant role in other signaling pathways , e . g . growth factor induced Erk activation , where Grb 2 can bind directly to the receptor tyrosine kinase and activate Erk in the absence of ShcA . ^^^ In a quest for molecules upstream of ShcA in this signaling , we found that CSR induced ShcA tyrosine phosphorylation , its association with Grb 2 , Erk activation , and uPA gene expression were all dependent on Rho kinase , p 38 mitogen activated protein kinase , and Src . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Apoptotic cell death influences the signaling activity of the amyloid precursor protein through ShcA and Grb 2 adaptor proteins in neuroblastoma SH SY5Y cells . ^^^ Among others , the interaction between tyrosine phosphorylated CTFs and ShcA Grb 2 adaptors is highly enhanced in AD brain . ^^^ Upon activation of apoptotic cell death this interaction is rapidly degraded , APP is partially cleaved and the complex APP / Grb2 is replaced by a new complex between CTFs and ShcA that still involves Grb 2 . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
BACE 1 expression is upregulated in AD brain , and we have recently shown in human brain and in vitro that BACE product CTFs , when phosphorylated in tyrosine residues , interact with the adaptor proteins ShcA and Grb 2 , which usually are involved in signal transduction pathways . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
Tyrosine phosphorylation generates a substrate that is sequentially bound by the adaptor proteins ShcA and Grb 2 , and this interaction is significantly enhanced in Alzheimer ' s disease brains . ^^^ Our data suggest the following : ( 1 ) in normally proliferating SH SY5Y cells , full length APP is complexed with Grb 2 [ Q 3 ] , likely through its SH 2 domain ; ( 2 ) upon induction of apoptosis , APP is degraded and ShcA Grb 2 coimmunoprecipitates with CTFs recognized by anti APP antibodies ; and ( 3 ) caspase inhibitors partially block the degradation of APP and the coprecipitation of CTFs with ShcA Grb 2 adaptors . ^^^ In summary , our data suggest that in SH SY5Y cells , tyrosine phosphorylated APP is involved in a complex with ShcA Grb 2 adaptors that is disrupted during apoptosis . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
It was shown that , following EGF stimulation , these cells exhibited decreased EGF receptor tyrosine phosphorylation , aberrant recruitment of the adaptor proteins ShcA and Grb 2 to the EGF receptor , reduced phosphorylation of ShcA and reduced Ras activation in comparison with control cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
We have recently described an interaction between tyrosine phosphorylated CTFs and ShcA adaptor protein which is highly enhanced in AD brain , and a new interaction between APP and the adaptor protein Grb 2 both in human brain and in neuroblastoma cultured cells . ^^^
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA
Interacting proteins: P29353 and P62993	Pubmed	SVM Score :0.0
NA