Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.64549678
Association of c Src with p52Shc in mitotic NIH3T3 cells as revealed by Src Shc binding site specific antibodies . 0.64549678^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.75103378
Concomitantly , Shc was observed to associate with a tyrosine phosphorylated 145 kDa protein , previously identified as Src homology 2 containing inositol phosphatase , only under conditions of negative signaling . 0.75103378^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.61738219
Immunoprecipitation experiments demonstrated functional differences between N Shc and Sck : ( 1 ) N Shc was a higher affinity adapter molecule than Sck in nerve growth factor and brain derived neurotrophic factor signaling ; and ( 2 ) N Shc , but not Sck , was efficiently phosphorylated by activated Src tyrosine kinase , whereas Sck , but not N Shc , formed a complex with pp 135 , a protein highly phosphorylated by 5 Src . 0.61738219^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.50562113
The association between Shc and LRP 1 may provide a mechanism for recruitment of Shc to the plasma membrane where it is phosphorylated by 5 Src . 0.50562113^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.52199359
Surprisingly , Src inhibition affected neither association of Shc with ErbB receptors nor phosphorylation of receptor bound Shc . 0.52199359^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The mammalian shc gene encodes two overlapping proteins of 46 and 52 kDa , each with a C terminal Src homology 2 ( SH 2 ) domain and an N terminal glycine / proline rich sequence , that induce malignant transformation when overexpressed in mouse fibroblasts . p46shc , p52shc , and an additional 66 kDa shc gene product become highly tyrosine phosphorylated in Rat 2 cells transformed by the 5 src or 5 fps oncogene . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The present studies demonstrate that IL 2 stimulation induces phosphorylation of the src homology 2 domain containing protein , p52shc , on both tyrosine and serine residues . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The Src homology 2 ( SH 2 ) domain containing Shc proteins p52shc and p46shc become phosphorylated upon activation of several tyrosine kinases and are implicated in mitogenic signal transduction . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The protein tyrosine phosphorylation pattern induced by IL 3 , IL 5 and GM CSF in these cell lines was shown to be remarkably similar and all three cytokines induced tyrosine phosphorylation of Shc , a src homology domain 2 containing protein which has been shown to be involved in Ras activation by tyrosine kinase receptors . . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
In vitro characterization of major ligands for Src homology 2 domains derived from protein tyrosine kinases , from the adaptor protein SHC and from GTPase activating protein in Ramos B cells . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
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 P12931 Pubmed SVM Score :0.0
EphB 1 recruits c Src and p52Shc to activate MAPK / ERK and promote chemotaxis . ^^^ 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 . ^^^ Site directed mutagenesis experiments demonstrate that tyrosines 600 and 778 of EphB 1 are required for its interaction with c Src and p52Shc . ^^^ Furthermore , phosphorylation of p52Shc by c Src is essential for its recruitment to EphB 1 signaling complexes through its phosphotyrosine binding domain . ^^^ Together these findings highlight a new aspect of EphB 1 signaling , whereby the concerted action of c Src and p52Shc activates MAPK / ERK and regulates events involved in cell motility . . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Our previous studies have shown that ectopic expression of the adaptor protein p52shc or p66shc , but not p46shc , and EGF stimulation lead to the activation of c Src that is accompanied by phosphorylation of signal transducers and activators of transcription ( Stat ) in A 431 cells . ^^^ Phosphorylation of Stat 3 / 5 in response to p52shc expression , EGF or H2O2 could also be inhibited by introduction into cells of phospho Tyr 845 specific antibody or by expression of dominant negative version of c Src . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
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 . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The purpose of this study was to determine if src homologous collagen like protein ( Shc ) was an in vivo substrate of the intestinal EGF receptor . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Src homologous and collagen ( Shc ) protein binds to F actin and translocates to the cytoskeleton upon nerve growth factor stimulation in PC 12 cells . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
One pathway by which ERKs 1 and 2 are activated by tyrosine kinases involves the Src homology ( SH ) 2 containing proteins SHC and Grb 2 . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The interaction is mediated by SHC amino acids 1 to 238 and is therefore independent of the Src homology 2 domain . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
MT forms complexes with protein phosphatase 2A ( PP2A ) , pp60c src , phosphatidylinositol 3 kinase , and Shc . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
IL 5 stimulation results in rapid tyrosine phosphorylation of beta c and proteins containing Src homology 2 ( SH 2 ) and / or SH 3 domains such as phosphatidyl inositol 3 kinase , Shc , Vav , and HS 1 , suggesting their involvement in IL 5 mediated signal transduction . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Consistent with suppression of pp60Src and pp53 / 56Lyn kinase activity , TGF beta also caused a substantial intracellular accumulation of the unphosphorylated form of SH 2 containing protein ( SHC ) , a substrate of the Src family kinases . ^^^ 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 P12931 Pubmed SVM Score :0.0
Previously , we showed that SH 2 domains expressed as recombinant glutathione S transferase fusion proteins ( GST SH 2 ) from GTPase activating protein , Shc , zeta chain associated protein tyrosine kinase Zap 70 , and Src like tyrosine kinases precipitated distinct sets of phospho proteins from activated B cells . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Shc is an adaptor protein that contains two phosphotyrosine binding domains , a Src homology 2 ( SH 2 ) domain and the newly described phosphotyrosine interaction ( PI ) domain . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
RESULTS : We have found that the Shc amino terminal region binds to a number of tyrosine phosphorylated proteins in 5 src transformed cells . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The insulin receptor phosphorylates insulin receptor substrate 1 ( IRS 1 ) and Shc on tyrosine residues , both of which associate with the protein abundant Src homology / growth factor receptor bound protein 2 ( ASH / GRB2 ) leading to p21ras activation . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) and src homology and collagen protein ( SHC ) are signaling proteins which are rapidly phosphorylated on tyrosines after insulin receptor ( IR ) activation . ^^^
Interacting proteins: P29353 and P12931 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 P12931 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 P12931 Pubmed SVM Score :0.0
Corresponding with Shc and PDGF receptor phosphorylation induced by angiotensin 2 was the recruitment and phosphorylation of c Src . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Cell transformation by middle T is strictly dependent on the ability of this protein to associate with cellular enzymes like members of the Src family of tyrosine kinases , a phosphatidylinositol 3 kinase , phosphatase 2A and SHC , an adapter protein linking GDP / GTP exchange factors to tyrosine kinase receptors . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Shc is a ubiquitously expressed Src homology 2 ( SH 2 ) domain protein that can transform fibroblasts and differentiate PC 12 cells in a Ras dependent fashion . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
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 . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Among these are members of the Src family of tyrosine kinases , the phosphatidylinositol 3 kinase , the serine / threonine phosphatase PP2A and the adaptor protein Shc ( in the case of MomT ) . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
Cytosolic Shc bound only GRB 2 , whereas , membrane associated Shc complexed with GRB 2 , the PDGF beta receptor , Src , and additional tyrosine phosphorylated proteins . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
METHODS : Immunodetection was used to compare the expression and tyrosine phosphorylation state of PLC gamma 1 , EGFR , phosphatidylinositol 3 kinase ( PI 3 kinase ) , ras guanosine triphosphatase activating protein ( GAP ) , and src homologous collagen like protein ( SHC ) in the postnatal rat intestine . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
This report demonstrates that NPTY is required for interaction between MT and SHC protein , a Src homology 2 ( SH 2 ) containing protooncogene product implicated in activating Ras via association with GRB 2 protein . ^^^ This result suggests that a complex exists that contains , at a minimum , MT , Src family tyrosine kinases , phosphatidylinositol 3 kinase , and SHC . . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Involvement of Src homology / collagen ( SHC ) proteins in signaling through the insulin receptor and the insulin like growth factor 1 receptor . ^^^ Src homology / collagen ( SHC ) proteins are thought to participate in signaling through both receptor tyrosine kinases , such as the insulin receptor and the EGF ( epidermal growth factor ) receptor , and cytoplasmic tyrosine kinases , such as 5 src and 5 fps . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The importance of epidermal growth factor ( EGF ) receptor expression level and autophosphorylation sites in src homology and collagen protein ( SHC ) tyrosine phosphorylation has been studied . ^^^ 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 P12931 Pubmed SVM Score :0.0
In order to explore the signaling mechanism from tyrosine kinase to Ras activation in more detail , interactions between two adaptor molecules , Shc and Grb2 / Ash , which contain Src homology regions , and their interactions with the NGF and EGF receptors were examined . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
Mutagenesis of the specific binding sites for these src homology 2 ( SH 2 ) domain containing substrates within the Trk cytoplasmic domain suggests a non essential function of PI3 ' K and reveals a major role for the signal controlled by the SHC binding site at tyrosine 490 and a co operative function of the PLC gamma mediated pathway for neuronal differentiation of PC 12 cells . . ^^^
Interacting proteins: P29353 and P12931 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 . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
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 ) . ^^^ Because several Src family kinases participate in T cell activation and Shc functions upstream of Ras , the role of Shc in T cell signaling was examined . ^^^ The Src homology region 2 ( SH 2 ) domain of Shc directly interacted with the tyrosine phosphorylated zeta chain of the TCR . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
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 . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Another transformation defective mutant encoding a middle T that retains functional binding of both pp60c src and PI 3 kinase but is incapable of binding Shc ( a protein involved in activation of Ras ) induced 2DG transport to wild type levels . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Shc could interact with the activated receptors through the carboxyl terminal Src homology 2 ( SH 2 ) domain or the structurally unrelated amino terminal phosphotyrosine binding ( PTB ) domain . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
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 . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
One of the proteins , middle T antigen , has been shown to bind cellular proteins involved in cell signalling such as c Src , phosphatase 2A , phosphatidylinositol 3 kinase and SHC . ^^^
Interacting proteins: P29353 and P12931 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 . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Shc is an Src homology 2 ( SH 2 ) domain protein thought to be an important component of the signaling pathway leading from cell surface receptors to Ras . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The Shc adaptor protein contains two phosphotyrosine [ Tyr ( P ) ] binding modules an N terminal Tyr ( P ) binding ( PTB ) domain and a C terminal Src homology 2 ( SH 2 ) domain . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The p80 / p85 / PI 3 kinase and the Shc / Grb2 / p140 complexes were tightly associated with Src family kinases , which were prime candidates for phosphorylation of Shc , p 80 , p 140 and other phosphotyrosyl substrates present in these complexes . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
A mammalian adaptor protein with conserved Src homology 2 and phosphotyrosine binding domains is related to Shc and is specifically expressed in the brain . ^^^ The Shc adaptor protein , hereafter referred to as ShcA , possesses two distinct phosphotyrosine recognition modules , a C terminal Src homology 2 ( SH 2 ) domain and an N terminal phosphotyrosine binding ( PTB ) domain , and is itself phosphorylated on tyrosine in response to many extracellular signals . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
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 . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Both Shc and p 190 are substrates of activated src and once phosphorylated , they interact with other proteins and upregulate p21ras . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
EGF stimulation also induced the association of Cbl with Src homology and collagen ( Shc ) protein , p 85 subunit of the phosphatidylinositol 3 kinase and Crk proteins , in particular with the CrkL isoform . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Immunoblots for coprecipitated proteins in Shc immunoprecipitates revealed a transient association of Shc and c Src following LPA stimulation , which coincided with increases in Shc associated tyrosine kinase activity and Shc tyrosine phosphorylation . ^^^ Overexpression of wild type or constitutively active mutant c Src , but not kinase inactive mutant c Src , lead to increased tyrosine kinase activity in Shc immunoprecipitates , increased Shc tyrosine phosphorylation , and Shc . ^^^ These data suggest that Gbetagamma subunit mediated formation of Shc . c Src complexes and c Src kinase activation are early events in Ras dependent activation of MAP kinase via pertussis toxin sensitive G protein coupled receptors . . ^^^ Coexpression of Csk , which inactivates Src family kinases by phosphorylating the regulatory C terminal tyrosine residue , inhibited LPA stimulation of Shc tyrosine phosphorylation , Shc . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
To clarify the functional importance of three distinct Shc domains on insulin and EGF signaling , we microinjected glutathione S transferase ( GST ) fusion proteins containing the amino terminus plus collagen homology domain ( NCH ) , collagen homology domain ( CH ) , and Src homology 2 domain ( SH 2 ) into Rat 1 fibroblasts expressing insulin receptors ( HIRc ) . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
To identify the initial steps of the mT induced signaling pathway ( s ) leading to this inhibition , T51B cells were transfected with vectors encoding the NG 59 , dl 23 , and 248M mT mutants , which are known to interact in a differential manner with c Src , P 13 kinase , and Shc . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Functional roles of the Shc phosphotyrosine binding and Src homology 2 domains in insulin and epidermal growth factor signaling . ^^^ Shc contains two phosphotyrosine binding domains , an Src homology 2 ( SH 2 ) domain in the carboxyl terminus of the protein and a phosphotyrosine binding ( PTB ) domain in the amino terminus . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Angiogenic growth factors and their receptors , such as basic fibroblast growth factor ( bFGF ) and Flg , vascular endothelial growth factor ( VEGF ) and Flk 1 , platelet derived growth factor ( PDGF ) B chain and PDGF beta receptor , and five intracellular signal proteins ( phosphatidylinositol 3 kinase [ PI3K ] , phospholipase C gamma [ PLC gamma ] , C Src , SHC , and mitogen activated protein kinase [ MAPK ] ) were examined by Western blot analysis . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
H Dependent self association of the Src homology 2 ( SH 2 ) domain of the Src homologous and collagen like ( SHC ) protein . ^^^ The Src homologous and collagen like ( SHC ) protein plays an essential role in signal transduction pathways in that it participates in the chain of events that leads to the activation of the protein Ras . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
An interaction between mDab 1 and Src is observed when P 19 embryonal carcinoma ( EC ) cells undergo differentiation into neuronal cell types . mDab 1 can also form complexes with cellular phosphotyrosyl proteins through a domain that is related to the phosphotyrosine binding ( PTB ) domains of the Shc family of adaptor proteins . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Inhibition of endogenous Src family kinase activity by cellular expression of a dominant negative kinase inactive mutant of c Src inhibits Gbeta1gamma2 subunit mediated and Gi coupled receptor mediated phosphorylation of both EGF receptor and Shc . ^^^ 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 P12931 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 P12931 Pubmed SVM Score :0.0
Each part of the retina was prepared for Western blot analysis of tyrosine phosphorylated proteins , vascular endothelial growth factor ( VEGF ) , basic fibroblast growth factor ( bFGF ) , and four signal proteins in the tyrosine kinase pathways , which were phospholipase C gamma ( PLC gamma ) , C Src , SH 2 containing protein ( SHC ) , and mitogen activated protein kinase ( MAPK ) . ^^^ The C Src and SHC were not activated in the retina after BVO . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The Src homology 2 ( SH 2 ) domain of SH 2 containing inositol phosphatase ( SHIP ) is essential for tyrosine phosphorylation of SHIP , its association with Shc , and its induction of apoptosis . ^^^ In this study we have investigated the role that the Src homology 2 domain ( SH 2 ) of the 145 kDa 5 phosphatase , SH 2 containing inositol phosphatase ( SHIP ) , plays in three of the properties that have been associated with this protein following cytokine stimulation : its association with Shc , its tyrosine phosphorylation , and its inhibition of hemopoietic cell growth . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
In membrane binding assays , fusion proteins containing the Src homology 2 domains of phospholipase C gamma 1 , Shc , Syk , and Lyn directly bound the tyrosine phosphorylated ITAM peptides . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Activation of ERK 1 and 2 may involve the Src homology 2 containing proteins Shc and Grb 2 . ^^^ Moreover , Shc associated both in vivo and in vitro with phosphorylated gp 130 through the Shc Src homology 2 domain . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
Although 5 src is a more potent inducer of tyrosine phosphorylation than c src 527 , the extent of phosphorylation of either insulin receptor substrate 1 or Shc , two of the major substrates of the IGF 1 receptor , does not seem sufficiently different to explain the qualitative difference in soft agar growth . 5 src , however , is considerably more efficient than c src 527 in its ability to tyrosyl phosphorylate , in R cells , the focal adhesion kinase , Stat 1 , and p130cas . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
In the nontransformed intestinal cell line IEC 6 , expression of EGFR , Src homology and collagen protein ( SHC ) , phospholipase C gamma 1 ( PLC gamma ) , and their tyrosine phosphorylation in response to EGF was assayed by immunoblot . ^^^
Interacting proteins: P29353 and P12931 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 . ^^^ Little is known about the tyrosine phosphorylations involved , although Src activation and Shc phosphorylation are thought to be critical . ^^^ Expression of dominant negative Src or Shc does not affect MAP kinase activation by LPA . ^^^ Thus , Gi mediated Ras / MAP kinase activation in fibroblasts and COS cells involves neither Src nor Shc . ^^^ Our results suggest that the p 100 Grb2 complex , together with an upstream non Src tyrosine kinase and PI 3 kinase , couples Gi to Ras / MAP kinase activation , while Src and Shc act in a different pathway . . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
To elucidate the growth signal transduction pathway downstream of c Src , tyrosine phosphorylation of Shc was examined in U 937 ASRC cells treated with Dexa . ^^^ The decline in c Src by induction of antisense src RNA expression decreased the level of tyrosine phosphorylation of Shc . ^^^ Immunoprecipitated c Src directly phosphorylated immunoprecipitated Shc on tyrosine residues in vitro . ^^^ 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 . . ^^^ 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 . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Shc interaction with Src homology 2 domain containing inositol phosphatase ( SHIP ) in vivo requires the Shc phosphotyrosine binding domain and two specific phosphotyrosines on SHIP . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Phosphatidylinositol 4 , 5 bisphosphate stimulates phosphorylation of the adaptor protein Shc by c Src . ^^^ The adaptor protein Shc was prepared as glutathione S transferase fusion proteins ( GST Shc ) and used as in vitro substrate for c Src . ^^^ Since phosphotyrosine binding domain of Shc has been shown to bind phosphatidyl inositol 4 , 5 bisphosphate ( PtdIns ( 4 , 5 ) P 2 ) [ Zhou et al . ( 1995 ) Nature 378 , 584 592 ] , effect of PtdIns ( 4 , 5 ) P 2 on the phosphorylation of GST Shc by c Src was examined . ^^^ PtdIns ( 4 , 5 ) P 2 stimulated the phosphorylation of GST Shc without any effect on the c Src activity as judged by both its autophosphorylation and phosphorylation of exogenous substrate , Cdc 2 peptide . ^^^ These results suggest that PtdIns ( 4 , 5 ) P 2 can act as a regulator of phosphorylation of Shc by c Src through its binding to Shc . . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
From our binding studies using synthetic peptides , we conclude that 3 phosphohistidine can not replace phosphotyrosine in conferring high affinity binding to the phosphotyrosine binding domain of shc or the src homology 2 domain of phospholipase C gamma1 . . ^^^
Interacting proteins: P29353 and P12931 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 . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
In the 10T model , preferred substrates of c Src are almost exclusively comprised of those molecules that associate with the actin cytoskeleton or with focal adhesions , such as cortactin , p190RhoGAP , and p130CAS , while preferred substrates of the EGF receptor include the receptor itself , SHC , phospholipase C gamma and p62DOK . ^^^ While the major mitogenic signaling pathway is thought to proceed directly from the receptor ( through SHC / GRB2 / SOS / Ras / Raf / MEK / MAPkinase / Elk1 ) , more evidence is accumulating to suggest that proteins involved in regulating the actin cytoskeleton ( such as c Src substrates ) also participate in mitogenesis , either as unique transducers of growth signals and / or as monitors of anti apoptotic conditions ( substratum attachment ) . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The presence of a type 1 ' turn in the BG loop , which is dependent on the presence of a glycine residue at position BG 3 , is indicative of a binding pocket , characteristic of the Src family , SykC and Abl , rather than a binding groove found in PLC gamma 1C , p 85 alpha N and Shc , for example . . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Tyrosine residues 239 and 240 of Shc are phosphatidylinositol 4 , 5 bisphosphate dependent phosphorylation sites by c Src . ^^^ In the previous study ( Sato K . 1 . et al . ( 1997 ) FEBS Lett . 410 , 136 140 ) , we showed that the phosphorylation of Shc protein by c Src is dependent on the binding of phosphatidylinositol 4 , 5 bisphosphate ( PtdIns ( 4 , 5 ) P 2 ) to the PTB domain of Shc . ^^^ In this study , we demonstrate that , in contrast to c Src , 5 Src and epidermal growth factor ( EGF ) receptor can phosphorylate Shc in a PtdIns ( 4 , 5 ) P 2 independent manner and at different phosphorylation sites . ^^^ We found that Y317F Shc but not Y239 / 240F or Y239 / 240 / 317F Shc was phosphorylated by c Src . ^^^ These results highlight the difference between c Src and 5 Src or EGF receptor and suggest that c Src can phosphorylate predominantly on Tyr239 / 240 of Shc only when Shc PTB domain is bound to PtdIns ( 4 , 5 ) P2 . . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Middle T has been shown to interact with a variety of cellular proteins known to mediate mitogenic signaling , like phosphatase 2A , Src family kinases , phosphatidylinositol 3 kinase ( PI 3 kinase ) , the adapter protein SHC , phospholipase Cgamma 1 and 14 3 3 family proteins . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
In cardiac fibroblasts , Ang 2 activates ERKs through a pathway including the Gbetagamma subunit of Gi protein , tyrosine kinases including Src family tyrosine kinases , Shc , Grb 2 , Ras , and Raf 1 kinase , whereas Gq and protein kinase C are important in cardiac myocytes . . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Furthermore , Src is required for the PDGF dependent phosphorylation of signaling molecules such as Shc . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
VD treatment also induced tyrosine dephosphorylation of Src and a formation of an Src Shc Grb 2 complex . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
We conclude that the initial burst of Src activity is required for efficient tyrosine phosphorylation of receptor associated proteins such as PLCgamma , RasGAP , Shc , and SHP 2 and for maximal activation of Erk . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The potent transforming activity of PyV MT is correlated with its capacity to activate and associate with a number of signaling molecules , including the Src family tyrosine kinases , the 85 kDa Src homology 2 subunit of the phosphatidylinositol 3 ' ( PI 3 ' ) kinase , and the Shc adapter protein . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The adaptor protein Shc contains a phosphotyrosine binding ( PTB ) domain and a Src homology 2 ( SH 2 ) domain , both of which are known to interact with phosphorylated tyrosines . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Recent data suggest that the I4R motif encodes binding sites for several protein tyrosine binding ( PTB ) domain containing proteins such as IRS 1 and Shc and potentially for the Src homology 2 domain of signal transducer and activator of transcription 6 ( STAT 6 ) . ^^^
Interacting proteins: P29353 and P12931 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 . ^^^ Interestingly , c Src in vitro phosphorylation of Shc promoted Grb 2 binding to both wild type and Phe 317 Shc . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Further analysis of signaling events revealed that phosphorylation of the HER 1 substrate , Shc , and its downstream effector , mitogen activated protein kinase , was increased in EGF stimulated MDA MB 468 , MDA MB 231 , and BT 549 cells ( which overexpress both c Src and HER 1 ) as compared with MCF 7 and ZR 75 1 cells ( which only overexpress c Src ) . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Insulin receptor substrate 1 antisense expression in an hepatoma cell line reduces cell proliferation and induces overexpression of the Src homology 2 domain and collagen protein ( SHC ) . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
Shc interaction with activated receptor tyrosine kinases is mediated by two distinct phosphotyrosine interaction domains , an NH 2 terminal phosphotyrosine binding ( PTB ) domain and a COOH terminal Src homology 2 ( SH 2 ) domain . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
At the onset of transformation polyomavirus middle T recruits shc and src to a perinuclear compartment coincident with condensation of endosomes . ^^^ At this time , expression of middle T antigen resulted in the redistribution of shc and src to a brefeldin A resistant perinuclear compartment coincident with the formation of kinase active complexes containing middle T antigen , shc and src . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
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 P12931 Pubmed SVM Score :0.0
To investigate early signaling mechanisms used by the EGFR in prostate tumor cells , we have characterized the involvement of the Shc ( src homology 2 / x collagen related ) adapter protein in EGFR signaling in several human prostate tumor cell lines . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Some of these proteins were identified as the Src Homology Collagen ( SHC ) protein , Janus kinase ( JAK 2 ) and the Mitogen Activated Protein Kinase isoforms ERK 1 and ERK 2 . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Previous studies have shown that the polyomavirus derived oncoprotein , middle T antigen ( mT ) , transforms rodent fibroblasts by interacting with and activating several cytoplasmic signaling proteins ( Src kinases , phospholipase C ( PLC ) gamma 1 , Shc , and phosphoinositide 3 kinase ( PI 3 K ) implicated in cell growth control . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Our previous studies have shown that the tyrosine kinase c Src phosphorylates Shc in a phosphatidylinositol ( PtdIns ) 4 , 5 bisphosphate dependent manner . ^^^ Here we demonstrate that PtdIns 3 , 4 , 5 trisphosphate stimulates phosphorylation of Shc by c Src . ^^^ These results suggest that coordinate action of PtdIns 3 kinase and / or PtdIns 3 , 4 , 5 trisphosphate and c Src can function as positive regulator in tyrosine phosphorylation of Shc in vitro and in vivo . . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Effect of nutritional state on the formation of a complex involving insulin receptor IRS 1 , the 52 kDa Src homology / collagen protein ( Shc ) isoform and phosphatidylinositol 3 ' kinase activity . ^^^ The Src homology and collagen protein ( Shc ) is tyrosine phosphorylated in response to insulin ; however , evidence for its interaction with insulin receptor ( IR ) in normal tissues is missing . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
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 . ^^^
Interacting proteins: P29353 and P12931 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 P12931 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 P12931 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 . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
SHC contains two phosphotyrosine interaction domains : a PTB ( Phosphotyrosine Binding ) and a SH 2 ( Src Homology 2 ) domain . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Protein interactions of Src homology 2 ( SH 2 ) domain containing inositol phosphatase ( SHIP ) : association with Shc displaces SHIP from FcgammaRIIb in B cells . ^^^ Our recent studies revealed that the inositol phosphatase Src homology 2 ( SH 2 ) domain containing inositol phosphatase ( SHIP ) is phosphorylated and associated with Shc exclusively under negative signaling conditions in B cells , which is due to recruitment of the SHIP SH 2 domain to the FcgammaRIIb . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
A novel SH 2 containing phosphatidylinositol 3 , 4 , 5 trisphosphate 5 phosphatase ( SHIP 2 ) is constitutively tyrosine phosphorylated and associated with src homologous and collagen gene ( SHC ) in chronic myelogenous leukemia progenitor cells . ^^^ We describe here the purification and mass spectrometric identification of a 155 kD tyrosine phosphorylated protein associated with src homologous and collagen gene ( SHC ) from p 210 ( bcr / abl ) expressing hematopoietic cells as SHIP 2 , a recently reported , unique SH 2 domain containing protein closely related to phosphatidylinositol polyphosphate 5 phosphatase SHIP . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The src homology domain 2 containing inositol phosphatase SHIP forms a ternary complex with Shc and Grb 2 in antigen receptor stimulated B lymphocytes . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The activation of overexpressed wild type IGF IR , but not that of an ATP binding mutant of IGF IR , resulted in the increased tyrosine phosphorylation of several intracellular proteins , including SHC , Src homology 2 containing inositol 5 phosphatase , protein kinase C delta , and Erk 2 . ^^^
Interacting proteins: P29353 and P12931 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 P12931 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 . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
Src homology and collagen protein ( Shc ) and messenger were not altered . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Expression of Csk , which inactivates Src family kinases , totally inhibited gastrin induced Src like activity detected in anti Src and anti Shc precipitates but diminished by 50 % Shc phosphorylation and ERK 1 activation . ^^^ One requires Shc phosphorylation by Src family kinases , and the other one is independent of these two proteins . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Shc tyrosine phosphorylation and Ras activation by H ( 2 ) O ( 2 ) were also significantly reduced in Fyn / cells , but not altered in Src / cells . ^^^
Interacting proteins: P29353 and P12931 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 P12931 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 P12931 Pubmed SVM Score :0.0
It contains a protein interaction ( PI ) domain similar to the phosphotyrosine binding domain of the Shc oncoprotein , it is phosphorylated by the Src protein tyrosine kinase , and it binds to SH 2 domains in a phosphotyrosine dependent manner . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
SHC possesses two phosphotyrosine binding domains : an amino terminal phosphotyrosine binding ( PTB ) and a carboxy terminal Src Homology 2 ( SH 2 ) domain . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
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 . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Mutation of either Tyr 851 or Tyr 883 , but mostly the latter , decreased Src phosphorylation of cadherin and the binding of Shc to cadherin , as determined by Sepharose bead binding and gel overlay assays . ^^^ Of the two tyrosine residues , Tyr 883 is the major Src phosphorylation and Shc binding site . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The hormone mediates these effects by activation of signaling pathways which utilize , 1 ) adaptor molecules such as the insulin receptor substrates ( IRS ) , the Src and collagen homologs ( Shc ) , and the growth factor receptor binding protein 2 ( Grb 2 ) ; 2 ) lipid kinases such as phosphatidylinositol 3 kinase ( PI 3 Kinase ) ; 3 ) small G proteins ; and 4 ) serine , threonine , and tyrosine kinases . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Phosphorylation of Shc by Src family kinases is necessary for stem cell factor receptor / c kit mediated activation of the Ras / MAP kinase pathway and c fos induction . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Insulin signaling [ tyrosine phosphorylation of insulin receptor ( IR ) , insulin receptor substrate 1 ( IRS 1 ) , Src homology and collagen protein ( Shc ) and phosphatidyl inositol 3 ' kinase activity ( PI 3 ' kinase ) ] was studied in the liver and thigh muscles of fat ( FL ) and lean ( LL ) chickens . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
METHODS : The present experiments used an explant culture model of the developing rat cerebellum to test the hypothesis that ethanol decreases endogenous trophic support by limiting the availability of trophic factors , such as GDNF , or by altering the activation of key adapter proteins such as Shc ( Src homology domain carboxy terminal ) that couple GDNF binding to multiple intracellular signaling pathways . ^^^
Interacting proteins: P29353 and P12931 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 . ^^^
Interacting proteins: P29353 and P12931 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 . ^^^ The Src family tyrosine kinase inhibitor , PP 1 , was shown to completely inhibit Shc tyrosine phosphorylation , the Shc Grb 2 interaction , and the FcgammaR induced respiratory burst . ^^^ Our results provide the first evidence that the upstream activation of Src kinases is required for the modulation of the Shc Grb 2 interaction and the myeloid NADPH oxidase response . . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
The SH 2 ( src homology 2 ) domain of Shc is also critical for signaling , but not required for phosphorylation of Shc . ^^^ In both cell types , inhibition of src family member kinases by chemical inhibitors or microinjection block Shc phosphorylation and bromodeoxyuridine ( BrdU ) incorporation in response to thrombin . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
Also , c Src activated by EGF treatment or expression of constitutively activated Ral GTPase led to tyrosine phosphorylation of Stat 3 and cortactin , but not Shc or subsequent Erk activation . ^^^ In contrast , c Src activated by isoproterenol led to tyrosine phosphorylation of Shc and subsequent Erk activation , but not tyrosine phosphorylation of cortactin or Stat 3 . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Furthermore AG 1478 , a specific inhibitor of the EGF receptor kinase , blocked Erk 1 and Erk 2 activation . c Src kinase was not involved in the IL 8 mediated phosphorylation of the EGF receptor , but was critical for Shc phosphorylation and downstream Erk1 / 2 kinase activation . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Evidence to support different mechanisms of PDGFbeta R phosphorylation includes differences in the time course of PDGFbeta R phosphorylation , differing effects of inhibitors of the endogenous PDGFbeta R tyrosine kinase and Src family tyrosine kinases , differing results when the PDGFbeta R was directly immunoprecipitated ( PDGFbeta R antibody ) versus coimmunoprecipitated ( Shc antibody ) , and cell fractionation studies that suggested that the Shc . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
Most notably , G ( q / 11 ) induced ERK activation was sensitive to N 17 Ras and to expression of the C terminal Src kinase but also to other dominant negative mutants of signaling components localized upstream of Ras , like Shc and the EGFR . ^^^ However , Src did not contribute to Shc tyrosine phosphorylation . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
To address this problem , we transfected MCF 7 cells to express the noncatalytic carboxylterminal domain of focal adhesion kinase ( FAK ) , FAK ( Y397F ) , kinase defective c Src , or Shc FFF , all of which express dominant negative activity . ^^^ Both activities were rescued by co transfecting the cells to express constitutively active MEK 1 , indicating that FAK , c Src , and Shc are upstream of MEK . ^^^ Urokinase type plasminogen activator stimulates the Ras / Extracellular signal regulated kinase ( ERK ) signaling pathway and MCF 7 cell migration by a mechanism that requires focal adhesion kinase , Src , and Shc . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Indeed , three amino acids important for ligand binding in Src SH 3 were replaced in the Slap SH 3 sequence ; Slap SH 3 did not bind to the Src SH 3 partners p85alpha , Shc , and Sam 68 in vitro , and the chimeric tyrosine kinase Slap / SrcK , composed of SlapDeltaC fused to the SH 2 linker kinase sequence of Src , was not regulated in vivo . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
We found that the IGF 1 dependent tyrosine phosphorylation of 66 kDa Shc ( Src homology collagen ) was markedly increased by cAMP pretreatment , and that this change was mainly due to an increase in the levels of 66 kDa Shc protein . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
We studied the impact of 16 serine residues in HIR by mutation to alanine and co overexpression in human embryonic kidney ( HEK ) 293 cells together with the docking proteins insulin receptor substrate ( IRS ) 1 , IRS 2 , or ( SHC ) Src homologous and collagen like . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The Shc adaptor protein possesses 2 distinct phosphotyrosine ( pTyr ) recognition modules the pTyr binding ( PTB ) domain and the Src homology 2 ( SH 2 ) domain and multiple potential sites for tyrosine ( Tyr ) phosphorylation ( Tyr residues 239 , 240 , and 317 ) . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The hemopoietic specific Gads ( Grb 2 related adaptor downstream of Shc ) adaptor protein possesses amino and carboxyl terminal Src homology 3 ( SH 3 ) domains flanking a central SH 2 domain and a unique region rich in glutamine and proline residues . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Here we show that agonists of the CaR increase the kinase activity of Src and ERKs ( extracellular signal regulated kinases ) in rat OSE cells and promote association between tyrosine phosphorylated Shc and p120rasGAP . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
These changes are accompanied by cytoskeletal binding and phosphorylation of focal adhesion kinase ( FAK ) at Tyr 397 and Tyr 925 , c Src at Tyr 416 , recruitment of the adapter proteins p 130 ( Cas ) , Shc , and Nck , and activation of the extracellular regulated kinases ERK1 / 2 . ^^^ Whereas cardiocytes under both conditions showed RGD stimulated ERK1 / 2 activation , only collagen embedded cells exhibited cytoskeletal assembly of FAK , c Src , Nck , and Shc . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Adaptor protein Shc undergoes translocation and mediates up regulation of the tyrosine kinase c Src in EGF stimulated A 431 cells . ^^^ In our previous studies , Shc was shown to be a substrate of the tyrosine kinase c Src in vitro and in vivo . ^^^ Indirect immunofluorescent study demonstrated that all Shc isoforms co localize with EGF receptor ( EGFR ) and activated c Src in both plasma membranes and cytoplasmic vesicle structures . ^^^ An immunoprecipitation study demonstrated that the EGFR Src association and c Src activation are augmented in cells expressing GFP Shc P 52 or P 66 , but not P 46 . ^^^ We also found that EGFR and Shc can be dissociated from c Src by the addition of a synthetic peptide that corresponds to the autophosphorylation site of c Src . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Since insulin is a key hormone for adipocyte conversion , and IRS 1 ( insulin receptor substrate 1 ) and Shc ( Src homology collagen ) proximal intracellular substrates of the insulin receptor control cell proliferation , the aim of this study was to investigate the role of IRS 1 and Shc in the early steps of differentiation . ^^^
Interacting proteins: P29353 and P12931 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 P12931 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 P12931 Pubmed SVM Score :0.0
One protein , the adaptor Shc , was a substrate for both Src family kinases ( on tyrosines 239 and 240 ) and a distinct tyrosine kinase ( on tyrosine 317 , which is perhaps phosphorylated by the PDGF receptor itself ) . ^^^ These inhibitions were overcome by heterologous expression of Myc , supporting the hypothesis that Shc functions in the Src pathway . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Tyrosine phosphorylation of Src homologous and collagen ( Shc ) , extracellular signal regulated kinase ( ERK ) 1 and ERK 2 , and phospholipase C gamma 1 ( PLC gamma 1 ) was increased by the three neurotrophins and the increase was inhibited in the presence of K252a . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
We assessed the roles of insulin receptor substrate 1 ( IRS 1 ) and Shc in insulin action on farnesyltransferase ( FTase ) and geranylgeranyltransferase 1 ( GGTase 1 ) using Chinese hamster ovary ( CHO ) cells that overexpress wild type human insulin receptors ( CHO hIR WT ) or mutant insulin receptors lacking the NPEY domain ( CHO DeltaNPEY ) or 3T3 L 1 fibroblasts transfected with adenoviruses that express the PTB or SAIN domain of IRS 1 and Shc , the pleckstrin homology ( PH ) domain of IRS 1 , or the Src homology 2 ( SH 2 ) domain of Shc . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
These results suggest that Sck , but not N Shc nor Shc , transmit signals in conjunction with pp 135 following Src activation and / or calcium entry in the cell . . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
In addition , we report that , upon direct or antibody dependent target cell interaction , shc coprecipitates with the Src homology 2 ( SH 2 ) containing inositol phosphatase , SHIP . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The Src family of nonreceptor tyrosine kinases has been shown to mediate the mitogenic effects of other growth factors that also activate Shc and the ERK 1 and 2 MAPKs . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Ang 2 caused a rapid tyrosine phosphorylation of Src homology and collagen ( Shc ) , which was inhibited by quercetin . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Moreover , PP 2 ( 20 nM ) , an inhibitor of Src , blocked D ( 4 ) receptor mediated SHC phosphorylation and ERK activation . ^^^ We also demonstrated that D ( 4 ) receptor stimulated cell proliferation is mediated by the Src / SHC / Ras / ERK pathway . . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
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 . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Using a GST fusion protein carrying the cytoplasmic tail of beta dystroglycan , we identified five SH 2 domain containing proteins that interact with beta dystroglycan in a phosphorylation dependent manner , including c Src , Fyn , Csk , NCK , and SHC . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Since growth factor induced MAPK activation involves signaling via the adapter protein Shc ( Src homology and collagen homology ) and its association with membrane receptors , we hypothesized that breast cancer cells utilize similar signaling mechanisms in response to E 2 . ^^^ Using selective inhibitors , we also demonstrated that ERalpha and Src are upstream regulators of Shc . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Down regulation of insulin receptor substrates ( IRS ) 1 and IRS 2 and Src homologous and collagen like protein Shc gene expression by insulin in skeletal muscle is not associated with insulin resistance or type 2 diabetes . ^^^ To examine whether altered gene expression of insulin receptor substrates ( IRS ) 1 and IRS 2 and Src homologous and collagen like protein Shc is an inherited trait and is associated with muscle insulin resistance or type 2 diabetes , we measured mRNA levels of these genes by a relative quantitative RT PCR method in muscle biopsies taken before and after an insulin clamp from 12 monozygotic twin pairs discordant for type 2 diabetes and 12 control subjects . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Co expression of Kv1 . 3 plus 5 Src with n Shc did not significantly alter 5 Src induced Kv1 . 3 current suppression but reversed 5 Src induced increased tau ( inact ) and restored the right shifted voltage at half activation ( 5 ( 1 / 2 ) ) induced by 5 Src . ^^^ The 5 Src induced shift in 5 ( 1 / 2 ) and increased tau ( inact ) was retained when Tyr ( 220 ) , Tyr ( 221 ) , and Tyr ( 304 ) in the CH domain of n Shc were mutated to Phe ( triple Shc mutant ) but was reversed back to control values when either wild type Shc or the family member Sck , which is not a substrate for Src kinase , was substituted for the triple Shc mutant . ^^^ Thus the portion of the CH domain that includes Tyr ( 220 ) , Tyr ( 221 ) , and Tyr ( 304 ) may regulate a shift in Kv1 . 3 voltage dependence and inactivation kinetics produced by n Shc in the presence of 5 Src . ^^^ Collectively these data indicate that Grb 10 and n Shc adaptor molecules differentially modulate the degree of Kv1 . 3 tyrosine phosphorylation , the channel ' s biophysical properties , and the physical complexes associated with Kv1 . 3 in the presence of Src kinase . . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Middle T antigen is the oncogenic protein of Polyomavirus and associates with several cellular enzymes involved in signal transduction , e . g . , Src tyrosine kinases , phosphatidylinositol 3 kinase ( PI 3 kinase ) , protein phosphatase 2A ( PP2A ) , and Shc , an SH 2 domain containing adapter protein . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
EGFR was Ca ( 2+ ) independently activated and predominantly contributed to Shc / ERK / c fos activation , while Pyk 2 or c Src contributed less to it . . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Discoidin domain receptor 2 interacts with Src and Shc following its activation by type 1 collagen . ^^^ Here we show that DDR 2 is also unusual in that it requires Src activity to be maximally tyrosine phosphorylated , and that Src activity also promotes association of DDR 2 with Shc . ^^^ These results identify Src kinase and the adaptor protein Shc as key signaling intermediates in DDR 2 signal transduction . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Pull down experiments with different Shc domains and mutants of the VE cadherin cytoplasmic tail have shown that Shc binds to the carboxy terminal domain of the VE cadherin tail through its Src homology 2 domain ( SH 2 ) . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The protein content of insulin receptors and SRC homology adaptor protein ( SHC ) did not change significantly along the time frame analyzed . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
Src activity initiates a signal transduction cascade , involving the adaptor protein Shc , which culminates in the transcriptional activation of the transcription factor Myc . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The Src homology 2 ( SH 2 ) domain containing inositol 5 ' phosphatase ( SHIP ) , which acts as the gatekeeper of degranulation , binds via both its SH 2 domain and its phosphorylated NPXY motifs to the adapter protein Shc via the latter ' s phosphorylated tyrosines and phosphotyrosine binding domain , respectively . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Adaptor protein Shc is an isoform specific direct activator of the tyrosine kinase c Src . ^^^ We show here that the Shc adaptor protein is a novel direct activator of c Src in epidermal growth factor receptor signaling in A 431 human epidermoid carcinoma cells . ^^^ Among the three Shc isoforms , P 66 and P 52 , but not P 46 , were found to interact with and activate c Src in vitro and in vivo . ^^^ We have identified the interaction sites between Shc and c Src and constructed a point mutant of Shc that abolishes the c Src activation . ^^^ Using this mutant , we have confirmed that the Shc mediated c Src activation triggers Stat p21 / WAF1 / Cip1 pathway that has been implicated in the cell cycle arrest and apoptosis of epidermal growth factor stimulated A 431 cells . . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
The Src homology 2 ( SH 2 ) domain of Shc is necessary for PDGF and EGF mediated Shc phosphorylation , whereas the phosphotyrosine binding ( PTB ) domain is critical for the actions of insulin . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
An emerging family of adapter protein , Shc ( Src homology and collagen ) related molecules , i . e . , Shc / ShcA , Sck / ShcB , and N Shc / ShcC , has been implicated in various phosphotyrosine signal transduction mechanisms , including that for NTs . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
We investigated the tyrosine kinase receptor pathway by evaluating the protein expression of total and phosphorylated mitogen activated protein kinase ( MAPK ) isoform p44 / p42 ( e . g . , extracellular signal regulated kinase [ ERK ] 1 / 2 ) , the steroid receptor coactivator Src and Shc ( Src homology / collagen protein ) . ^^^ In vitro , 17 beta estradiol induced proliferation of isolated normal cholangiocyte was associated with increased ( P < . 01 ) protein expression of p ERK1 / 2 , Src , and Shc . ^^^ In conclusion , this study showed that estrogens induced cholangiocyte proliferation by activating the Src / Shc / ERK pathway . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
We extend this hypothesis to downstream signalling molecules activated by ligation of the alphaVbeta 3 integrin , some of which ( i . e . , Src , PYK 2 , and Shc ) could have similar specific roles in tumor cells , activated endothelium and osteoclasts , but not in other cell types . . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Binding of Src to Shc was required for its activation and for Ras dependent activation of ERK1 / 2 , cell proliferation , and wound recovery . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
SHIP 2 associated with the adapter protein Shc via its NPXY motif during cell spreading on collagen 1 in a Src activity dependent manner . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Membrane localization of Src homology 2 containing inositol 5 ' phosphatase 2 via Shc association is required for the negative regulation of insulin signaling in Rat 1 fibroblasts overexpressing insulin receptors . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
In this report we provide evidence that first , SHIP is indeed phosphorylated by ITAM FcgammaR , using cell systems that lack FcgammaRIIb expression ; second , coimmunoprecipitation experiments demonstrate that SHIP associates with native ITAM bearing FcgammaRIIa in vivo ; and third , phosphorylation of SHIP by FcgammaRIIa is inhibited by overexpressing either the SHIP Src homology 2 domain or a dominant negative mutant of Shc . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Ly GDI is phosphorylated on tyrosine residues following T cell receptor stimulation , and it associates with the Src homology 2 region of an adapter protein , Shc . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Through its Src homology 3 ( SH 3 ) and SH 2 domains , the Src kinase Lyn interacts with a small number of phosphoproteins , such as Shc , Cbl , and Vav , which regulate cell cycle and the cytoskeleton . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Here , we demonstrate that PP 1 , a selective inhibitor of Src family kinases , blocks the EGF induced Gab 2 tyrosine phosphorylation without inhibiting EGF induced phosphorylation of the EGF receptor , ErbB 3 , or Shc . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
In addition , the present study provides evidence that the Src family tyrosine kinase Yes is activated by CCK and mediates CCK induced tyrosine phosphorylation of Shc . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The kinetics of phosphorylation of Shc , previously demonstrated to be phosphorylated by Src downstream of c Kit , was stronger and more rapid in the GNNK form , whereas it showed slower kinetics in the GNNK+ form . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Upon JAK 2 activation , tyrosine phosphorylation of signal transducer and activator of transcription 1 ( STAT 1 ) , STAT 5b , insulin receptor substrate 1 ( IRS 1 ) , and Src homology and collagen homology ( Shc ) were detected . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
Using a combination of genetic and pharmacological approaches , we show herein that integrin signaling to Shc in T cells requires the receptor tyrosine phosphatase CD 45 , the Src family kinase member Lck , and protein kinase C . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
TGF beta did not impair proximal signaling by Shc or STAT 5 , and induction of some downstream genes , including cytokine inducible Src homology 2 containing protein ( CIS ) , bcl 10 ( L ) , and bcl 2 , was spared . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Src induces Shc binding to tyrosine 63 in the cytoplasmic domain of the LDL receptor related protein 1 . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The critical role of c Src and the Shc / Grb2 / ERK2 signaling pathway in angiotensin 2 dependent VSMC proliferation . ^^^ Recent evidence suggest that the tyrosine kinase c Src may mediate this proliferative response . c Src can signal through multiple intracellular signaling pathways including ( 1 ) the Shc / Grb2 / ERK2 pathway , ( 2 ) the signal transducers and activators of transcription ( STATs ) , ( 3 ) the focal adhesion kinase ( FAK ) signaling pathway , and ( 4 ) the phosphatidylinositol 3 kinase ( PI3K ) signaling pathway . ^^^ In this study , we sought to determine the extent to which c Src mediates vascular smooth muscle cell proliferation through the Shc / Grb2 / ERK2 signaling pathway . ^^^ Here we demonstrate that treatment of vascular smooth muscle cells with angiotensin 2 results in activation of the Shc / Grb2 / ERK2 signaling pathway as measured by ( 1 ) increased Shc tyrosine phosphorylation , ( 2 ) increased c Src / Shc cellular co localization , ( 3 ) increased Shc / Grb2 co association , and ( 4 ) ERK 2 activation . ^^^ Thus , the data suggest that c Src and the Shc / Grb2 / ERK2 signaling pathway play a critical role in angiotensin 2 mediated VSMC proliferation . . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
These include phosphorylation of src and PLCgamma leading finally to activation of PKC , as well as activation of Crk and Shc . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Our results point to the involvement of several ErbB specific ligands ( amphiregulin and neuregulin 1 ) and enzymes or adaptor molecules ( PI3K , Src , Shc and Grb 7 ) in the ErbB pathway dysregulation associated with breast cancer . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The in vivo interaction between PLSCR 1 and Shc requires the Src mediated phosphorylation on tyrosines 69 and 74 . ^^^ We propose that PLSCR 1 , through its interaction with Shc , promotes Src kinase activation through the EGF receptor . . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Src homology 2 / alpha collagen related protein ( Shc ) is the main mediator of IGF 1 mitogenic action , coupling IGF IR phosphorylation to Ras MAPK activation . ^^^ Src family kinases regulate IGF 1 action through an Shc dependent mechanism . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Integrin alpha6beta4 signaling proceeds through Src family kinase ( SFK ) mediated phosphorylation of the cytoplasmic tail of beta 4 , recruitment of Shc , and activation of Ras and phosphoinositide 3 kinase . ^^^
Interacting proteins: P29353 and P12931 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 . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The human Src homology and collagen ( Shc ) gene encodes three protein isoforms of 46 , 52 , and 66 kDa that belong to a family of molecular adapters involved in several signal transduction pathways . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Since these Shc isoforms have been implicated in the activation of protein kinase c Src , which is required for FAK tyrosine phosphorylation , the observed dephosphorylation of FAK and of the FAK substrate paxillin by OTA could be ascribed to the early down regulation of Shc isoforms . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Activated receptor tyrosine kinases bind the Shc adaptor protein through its N terminal phosphotyrosine binding ( PTB ) and C terminal Src homology 2 ( SH 2 ) domains . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
PAF exposure induced binding of p 130 ( Cas ) , Src , SHC , and paxillin to FAK . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
In this study , we observed that curcumin inhibited the kinase activity of 5 Src , which led to a decrease in tyrosyl substrate phosphorylation of Shc , cortactin , and FAK . ^^^ Consistent with the abrogation of Src activity was the reduction of Src Tyr 416 phosphorylation , Src mediated Shc Tyr 317 phosphorylation , decreased ERK activation , and cell proliferation in 5 Src transformed cells . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Further analysis demonstrated that , although TSA reduced the expression of Eps 8 in a dose and time dependent manner , both the protein expression and kinase activity of 5 Src remained constant , and the abundance and phosphotyrosine levels of Src substrates , including cortactin , focal adhesion kinase , p 130 ( Cas ) , paxillin , and Shc , were not altered . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Cell stimulation through CD 43 results in recruitment of different signaling proteins , including members of the Src family kinases , Syk , phospholipase Cgamma 2 , the adapter protein Shc , the guanine nucleotide exchange factor Vav , and activation of protein kinase C . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
We have now found that phosphorylation of Ser 585 of beta ( c ) in response to GM CSF recruited 14 3 3 and phosphatidyl inositol 3 OH kinase ( PI 3 kinase ) to the receptor , while phosphorylation of the neighboring Tyr 577 within this `` viability domain ' ' promoted the activation of both Src homology and collagen ( Shc ) and Ras . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The involvement of Shc in the pathway regulating APP processing is confirmed by the effects of constitutively active and dominant negative mutants of Src and Rac1 . . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
However , phosphorylation of Shc on Tyr ( 239 ) , the Src phosphorylation site , was normal . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
The expression of beta ( 1 ) integrin receptor , as well as Src , son of sevenless protein ( SOS ) and phosphorylated mitogen activated protein ( MAP ) kinases ( MAPK ) , extracellular signal regulated kinase 1 ( ERK ( 1 ) ) and kinase 2 ( ERK ( 2 ) ) but not focal adhesion kinase pp 125 ( FAK ) ( FAK ) , Shc , and Grb 2 was significantly decreased in cells incubated for 24 h with 10 microM AB ( 1 ) compared to the control , whereas in the same conditions chlorambucil did not evoke any changes in expression of all these signaling proteins , as shown by Western immunoblot analysis . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
In EGFR ( Y5F ) expressing cells , LPA failed to elicit tyrosine phosphorylation of Src homologous and collagen protein ( SHC ) and caused only a modest increase in ERK1 / 2 phosphorylation similar to that in wild type B82L cells . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
In some contexts , steroid receptors interact directly with c Src and other cytoplasmic signaling molecules , such as Shc , PI3K , and p 130 Cas . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
In R cells transiently expressing the Y1250F / Y1251F mutant RACK 1 became constitutively associated with beta 1 integrin and did not associate with Shc , Src , or Shp 2 . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
The frontier includes characterization of how scaffolding / adapter proteins , such as cbl , gab , grb , p130Cas , and shc , as well as itam containing proteins and nonreceptor tyrosine kinase adapters of the src and syk families , delimit and integrate signals of multiple receptors to bring about specific outcomes . . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
N Shc ( neural Shc ) ( also ShcC ) , an adapter protein possessing two phosphotyrosine binding motifs [ PTB ( phosphotyrosine binding ) and SH 2 ( Src homology 2 ) domains ] , is predominantly expressed in mature neurons of the CNS and transmits neurotrophin signals from the TrkB receptor to the Ras / mitogen activated protein kinase ( MAPK ) pathway , leading to cellular growth , differentiation , or survival . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
In the presence of estradiol ( E 2 ) , ERalpha , Src homology and collagen homology ( Shc ) , and insulin like growth factor receptor 1 proteins associate with and increase the localization of ERalpha at the membrane . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Here , we define a mechanism whereby integrin alpha 5 beta 3 , through activation , clustering , and signaling by means of p 66 Shc ( Src homology 2 domain containing ) , regulates the production of VEGF in tumor cells expressing this integrin . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
We previously found that EGF ( epidermal growth factor ) increases the EGFR ( EGF receptor ) kinase binding affinity towards the major tyrosine phosphorylation sites in downstream adaptor proteins such as Gab 1 ( Grb 2 associated binding protein 1 ) and Shc [ Src homology 2 ( SH 2 ) domain and collagen containing protein ] , but not that towards EGFR autophosphorylation sites [ Fan , Wong , Deb and Johnson ( 2004 ) J . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
C terminal Src kinase homologous kinase and the adaptor Shc bind to both phosphotyrosines 568 and 570 . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
Tyrosine 740 phosphorylation of discoidin domain receptor 2 by Src stimulates intramolecular autophosphorylation and Shc signaling complex formation . ^^^ Collectively , our findings are consistent with the following mechanism for Src dependent DDR 2 activation and signaling : 1 ) ligand binding promotes phosphorylation of Tyr 740 in the DDR 2 activation loop by Src ; 2 ) Tyr 740 phosphorylation stimulates intramolecular autophosphorylation of DDR 2 ; 3 ) DDR 2 autophosphorylation generates cytosolic domain phosphotyrosines that promote the formation of DDR 2 cytosolic domain Shc signaling complexes . . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
A critical step in this process is the phosphorylation of Tyr 397 of FAK , which creates a binding site for Src family kinases , PI3K ( phosphoinositide 3 kinase ) and Shc ( Src homology and collagen homology ) . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
They stimulate ERK , Shc , and Src phosphorylation in MCF 7 breast cancer cells at low concentrations , yet they are very ineffective in stimulating transcription of endogenous estrogen target genes , being approximately 10 , 000 fold less potent than estradiol in genomic actions . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
HRS was found to sequester PELP 1 in the cytoplasm , leading to the activation of MAPK in a manner that is dependent on the epidermal growth factor receptor but independent of the estrogen receptor , Shc , and Src . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
To elucidate the molecular basis for signaling specificity of GDNF mediated RET signaling in kidney development , we characterized mice that exclusively express either the human RET 9 or RET 51 isoform , or express these isoforms with individual mutations in docking tyrosines for PTB and SH 2 domain containing adaptors Src ( Y 981 ) , PLCgamma ( Y 1015 ) , and Shc ( Y 1062 ) . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Additionally , Y 228 in the YLSF sequence and Y 291 are IRK substrates ; the former sequence provides optimum recognition motif in the tyrosine phosphatase , SHP 1 , and for SHC ( Src homology 2 domain containing transfroming protein 1 ) . ^^^
Interacting proteins: P29353 and P12931 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 P12931 Pubmed SVM Score :0.0
We tested whether Shc is a substrate of c Src in SMC by disrupting Src / Shc association using a peptide containing a YXXL ( Tyr 328 ) motif sequence derived from Src . ^^^ Upon IGF 1 stimulation , a complex assembles on SHPS 1 that contains SHP 2 , c Src , and Shc wherein Src phosphorylates Shc , a signaling step that is necessary for an optimal mitogenic response . . ^^^ These studies were undertaken to determine whether Src kinase activity is required to phosphorylate Shc in response to IGF 1 in SMC and because SHP 2 binds to Src whether their interaction was also required for IGF 1 stimulated mitogenesis . ^^^ Our results show that IGF 1 induces activation of Src kinase and that is required for Shc phosphorylation and for optimal MAPK activation . ^^^ The peptide blocked the binding of Src and Shc in vitro and in vivo . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
Activation of Trk receptors leads to increased phosphorylation of Shc ( Src homology and collagen homology ) , phospholipase C gamma and novel adaptor molecules , such as the ARMS ( ankyrin rich membrane spanning ) / Kidins220 protein . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
We have recently described a novel ShcA like protein , ShcC , which like ShcA contains an NH 2 terminal phosphotyrosine binding domain ( PTB ) , a central effector region ( CH 1 ) and a COOH terminal Src homology 2 domain ( SH 2 ) . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
PymT , a membrane associated scaffold , recruits and activates Src family tyrosine kinases , and , once tyrosine phosphorylated , binds proteins with PTB and SH 2 domains such as ShcA , phosphatidylinositol 3 kinase ( PI3K ) and phospholipase Cgamma 1 ( PLCgamma 1 ) . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
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 P12931 Pubmed SVM Score :0.0
We show that activation of the recombinant lutropin / choriogonadotropin receptor ( LHR ) in mouse Leydig tumor cells ( MA 10 cells ) leads to the tyrosine phosphorylation of Shc ( Src homology and collagen homology ) and the formation of complexes containing Shc and Sos ( Son of sevenless ) , a guanine nucleotide exchange factor for Ras . ^^^ The LHR mediated phosphorylation of the EGFR and Shc , the activation of Ras , and the phosphorylation of ERK1 / 2 are inhibited by expression of a dominant negative mutant of Fyn , a member of the Src family kinases ( SFKs ) expressed in MA 10 cells and by PP 2 , a pharmacological inhibitor of the SFKs . ^^^
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
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Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA
Interacting proteins: P29353 and P12931 Pubmed SVM Score :0.0
NA