Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.5698004
From these results , we conclude that after insulin and EGF treatment , Shc associates with both Grb 2 and mSOS and therefore may mediate , at least in part , insulin and EGF induced activation of p21ras . 0.5698004^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.67834707
Like p52shc / p46shc , p66shc is tyrosine phosphorylated upon epidermal growth factor ( EGF ) stimulation , binds to activated EGF receptors ( EGFRs ) and forms stable complexes with Grb 2 . 0.67834707^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In contrast to EGF receptor and c erbB 2 , we were unable to detect binding of activated c erbB 3 to GRB 2 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
A Grb 2 associated docking protein in EGF and insulin receptor signalling . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In clones expressing high levels of mutant EGF receptor , the levels of both Grb 2 and SHC were decreased . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Following EGF or insulin stimulation , Shc is phosphorylated on single Tyr 317 residue serving as a docking site for Grb 2 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
We found that huntingtin is associated with Grb 2 , RasGAP , and tyrosine phosphorylated EGF receptor . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Shc phosphorylation and Grb 2 association after EGF treatment were present throughout all phases of growth . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
By contrast , Shc and Grb 2 were inducibly associated with the EGFR in response to EGF stimulation of glioma cells . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
TRH induced EGF receptor phosphorylation was found to lead to the recruitment of the adapter proteins Grb 2 and Shc . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Grb 2 and Shc ) are also degraded in an EGF induced Cbl b dependent fashion . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Activation of EGF receptors mediates pulmonary vasoconstriction induced by residual oil fly ash . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Ang 2 also increased the association of the adaptor protein Grb 2 with the EGF R . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
A mutant EGF receptor defective in ubiquitylation and endocytosis unveils a role for Grb 2 in negative signaling . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
The extent of colocalization of EGFR and Grb 2 with Hrs and clathrin varied with time of incubation with EGF . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
EGF induced association of Shc with the adapter protein Grb 2 may have implications for activation of the p21ras signaling pathway in the intestine . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Both TRH and EGF induced the association of tyrosine phosphorylated Shc proteins with a fusion protein containing SH 2 and SH 3 domains of Grb 2 , another important component in ras activation . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
We analyzed the binding site ( s ) for Grb 2 on the epidermal growth factor ( EGF ) receptor ( EGFR ) , using cell lines overexpressing EGFRs containing various point and deletion mutations in the carboxy terminal tail . ^^^ Since Grb 2 also binds Shc after EGF stimulation , we investigated whether Y 1173 is a binding site for the SH 2 domain of Shc on the EGFR . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Affinities are in the nanomolar range , the Shc peptide having the highest affinity , followed by peptides mimicking Grb 2 binding sites on EGF and HGF receptors , the putative sites on insulin and IGF 1 receptors having much lower affinities . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
This question is addressed through studies of the binding to intact Grb 2 of an EGF receptor derived phosphotyrosine containing peptide and a Sos derived proline rich peptide using isothermal titration calorimetry and surface plasmon resonance measurements . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Further , activation of the EGF receptor did not result in any significant tyrosine phosphorylation of SHPTP 2 and / or the association of the 115 kDa protein with Grb 2 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Consistent with these differences , Grb 2 predominantly bound to the 52 kDa Shc isoform following insulin stimulation , whereas Grb 2 associated with both the 52 and 46 kDa Shc isoforms after EGF stimulation . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
However , immunoblotting of anti Son of sevenless ( Sos ) 1 and 2 immunoprecipitates with anti Grb 2 antisera revealed that p21ras desensitization in response to insulin and PDGF , but not EGF , is associated with a marked decrease in cellular complexes containing Sos and Grb 2 proteins . ^^^ Insulin elicits dissociation of Sos from Grb 2 SH3 domains , whereas EGF signaling is reversed by receptor down regulation and Shc dephosphorylation , releasing Grb 2 SH2 domains . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
The association of the src homology 2 ( SH 2 ) domain containing tyrosine phosphatase ( SH PTP 2 ) with the activated epidermal growth factor ( EGF ) and platelet derived growth factor receptors , as well as the insulin receptor substrate 1 and growth factor receptor bound protein 2 and its intrinsic tyrosine phosphatase activity suggests an important role for this phosphatase in signal transduction . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Among these , the SHC adaptor protein was phosphorylated in absence of EGF , the other adaptor , GRB 2 was constitutively associated with the Glu 627 EGF receptor in vivo and in vitro , and mitogen activated protein kinase was constitutively phosphorylated . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Here we show that 5 Crk complexes with both the tyrosine phosphorylated EGF receptor and the Ras guanine nucleotide exchange factor SOS in PC 12 cells and is involved in an pathway analogous to that of Grb 2 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
We have investigated the association of the Grb 2 protein with epidermal growth factor ( EGF ) and nerve growth factor ( NGF ) receptors in PC 12 pheochromocytoma cells . ^^^ EGF treatment of PC 12 cells results in the rapid association of Grb 2 with the activated EGF receptors , an interaction mediated by the Grb 2 SH2 domain . ^^^ These results suggest that whereas EGF and NGF can activate the Ras signaling pathway in PC 12 cells , only the EGF receptor is likely to do so through a direct interaction with Grb 2 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
It is proposed that two of the critical steps of that pathway utilize localization of components to the plasma membrane where Ras is located : recruitment of the nucleotide exchange protein Sos to the phosphorylated EGF receptor via a complex with the SH2 / SH3 containing protein Grb 2 and recruitment of the protein kinase Raf to activated Ras . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Similarly , more Grb 2 was associated with Shc than with EGFR after EGF stimulation . ^^^ Immunoprecipitation of Shc from EGF stimulated cells removed almost all EGFR associated Grb 2 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
This approach has been demonstrated to work in vitro to interfere with SH 2 tyrosine phosphate interactions ( i . e . , Grb 2 and EGF receptor ) and Ras Raf interactions using specific peptides ( J . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Compartmentalization of SHC , GRB 2 and mSOS , and hyperphosphorylation of Raf 1 by EGF but not insulin in liver parenchyma . ^^^ Following administration of a saturating dose of EGF ( 10 micrograms / 100 g body weight ) , there was a rapid ( t1 / 2 approximately 1 . 1 min ) internalization of receptor coincident with its tyrosine phosphorylation at residue 1173 and receptor recruitment of the adaptor protein SHC , its tyrosine phosphorylation and its association with GRB 2 and the Ras guanine nucleotide exchange factor , mSOS , largely in endosomes . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In response to EGF treatment , complexes form between Sos , Grb 2 and tyrosine phosphorylated Shc and / or EGF receptor . ^^^ In streptolysin O permeabilised cells , a tyrosine phosphopeptide , EGFR Y1068P , which binds to the SH 2 domain of Grb 2 , totally blocks growth factor induced formation of complexes between Grb 2 and Shc or EGF receptor , and also blocks activation of nucleotide exchange on Ras . ^^^ Higher concentrations of TRK Y490P inhibit tyrosine phosphorylation of Shc and the formation of Shc complexes with Grb 2 : this results in strong inhibition of Ras activation by NGF and partial inhibition of Ras activation by EGF . ^^^ The binding of Sos to tyrosine phosphorylated receptor , via Grb 2 may also contribute to Ras activation by EGF but not NGF , while stable complex formation between Shc and receptors is not necessary for Ras activation by either growth factor . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
To assess whether EGF stimulates guanine nucleotide exchange by recruiting Grb 2 Sos complexes to the plasma membrane , we measured GEF activity in both the cytosol and the plasma membrane fractions of the insulin and EGF treated cells . ^^^ Western blotting of the subcellular fractions with Grb 2 and Sos antibodies revealed translocation of these elements to the plasma membrane after stimulation of cells with either insulin or EGF . ^^^ Thus , whereas insulin stimulates guanine nucleotide exchange on Ras by both translocating Grb 2 Sos complexes to the plasma membrane and increasing the GEF activity of Sos , EGF does so by causing a translocation of Grb 2 Sos without increasing GEF activity . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
The EGF receptor mutant Dc 214 is able to activate the ras guanine nucleotide exchanger and phosphorylate mitogen activated protein kinase ( MAPK ) , presumable as a result of complex formation between tyrosine phosphorylated SHC and GRB 2 . ^^^ Also , our data show that EGF receptors are able to phosphorylate SHC , activate the exchange of guanine nucleotide on ras and phosphorylate MAPK by a mechanism that does not require receptor autophosphorylation sites and , therefore , the src homology 2 ( SH 2 ) : phosphotyrosine dependent interaction of SHC or GRB 2 with the EGF receptor . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Ash / Grb 2 , a SH2 / SH3 containing protein , couples to signaling for mitogenesis and cytoskeletal reorganization by EGF and PDGF . ^^^ Consistent with this , Ash co precipitated with EGF receptor from EGF stimulated cells . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In response to epidermal growth factor ( EGF ) , the activated EGF receptor binds to a complex containing the signaling protein GRB 2 and the Ras guanine nucleotide releasing factor Sos , leading to activation of the Ras signaling pathway . ^^^ In contrast with the EGF receptor , the GRB 2 does not bind to the PDGF receptor directly . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
NGF and EGF also induced the association of Shc proteins with a Grb 2 fusion protein or endogenous Grb 2 , whereas insulin had no effect . ^^^ All of the tyrosine phosphorylated Shc proteins associated with the Grb 2 fusion protein , although only about half of the endogenous Shc was phosphorylated in response to NGF or EGF . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
The SH 2 and SH 3 domains of mammalian Grb 2 couple the EGF receptor to the Ras activator mSos 1 . ^^^ Sem 5 is homologous to the mammalian protein Grb 2 , which binds the autophosphorylated EGF receptor and other phosphotyrosine containing proteins such as Shc through its SH 2 domain . ^^^ EGF stimulation induces binding of the Grb 2 mSos1 complex to the autophosphorylated EGF receptor , and mSos 1 phosphorylation . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
The SH 2 and SH 3 domain containing `` adapter ' ' protein Grb 2 is also found in Sos immunoprecipitates in an EGF inducible manner . ^^^ In vitro reconstitution shows that Grb 2 is required for the binding of activated EGF receptor to Sos . ^^^ These results suggest that EGF induced activation of nucleotide exchange on p21ras proceeds through the recruitment of cytosolic Sos to a complex with EGF receptor and Grb 2 at the plasma membrane . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In contrast to results with Abl , Erk activation by EGF was strongly inhibited only by Grb 2 mutants ; Crk and Nck mutants had little or no effect . ^^^ This finding suggests that Grb 2 is the only adapter involved in the activation of Erk by EGF . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In response to stimulation with epidermal growth factor ( EGF ) , the guanine nucleotide exchange factor human SOS 1 ( hSOS 1 ) promotes the activation of Ras by forming a complex with Grb 2 and the human EGF receptor ( hEGFR ) . hSOS 1 was phosphorylated in cells stimulated with EGF or phorbol 12 myristate 13 acetate or following co transfection with activated Ras or Raf . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
While the ligand stimulated receptor tyrosine phosphorylation and interaction with downstream signaling molecules , such as GRB 2 , were not affected , IFNs specifically blocked PDGF and phorbol ester but not EGF stimulated activation of Raf 1 , mitogen activated protein kinases , and tyrosine phosphorylation of an unidentified 34 kDa protein . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Even though epidermal growth factor ( EGF ) also stimulates ERK activity and phosphorylation of SOS similar to insulin , EGF induces a dissociation of the Grb 2 SOS complex from Shc . ^^^ Although EGF stimulation of the mutant EGF receptor activates ERK and phosphorylation of both Shc and SOS , it fails to directly associate with either Shc or Grb 2 . ^^^ However , under these conditions EGF induces a dissociation of the Grb 2 SOS complex suggesting a role for receptor and / or plasma membrane targeting in the stabilization of Grb 2 SOS interaction . ^^^ Consistent with this hypothesis , expression of an SH 2 domain Grb 2 mutant which is unable to mediate plasma membrane targeting of the Grb 2 SOS complex results in both insulin and EGF stimulated uncoupling of Grb 2 from SOS . ^^^ Together , these data demonstrate that EGF stimulation prevents the feedback uncoupling of Grb 2 from SOS by inducing a persistent plasma membrane receptor targeting of the Grb 2 SOS complex . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Furthermore , we observed association of ACK with an adaptor protein Grb 2 , which may suggest the involvement of Grb 2 in EGF receptor mediated tyrosine phosphorylation of ACK . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Sos 1 rapidly associates with Grb 2 and is hypophosphorylated when complexed with the EGF receptor after EGF stimulation . ^^^ The C terminal region of Sos binds an adaptor protein , Grb 2 , which in turn binds to activated receptors including the EGF receptor ( EGFR ) . ^^^ Therefore , we investigated whether the ability of Sos 1 to form complexes with Grb 2 and with the EGF receptor ( EGFR ) changes following EGF stimulation , as a possible mechanism for regulating Sos activity . ^^^ In contrast to earlier findings , we find that both the association and dissociation of Sos 1 with Grb 2 is responsive to EGF . ^^^ Whilst the association of Sos 1 and Grb 2 following EGF stimulation is not cell type specific , we find that it is dependent on cell density and that the response to EGF differs to that induced by NGF . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Requirement for the adapter protein GRB 2 in EGF receptor endocytosis . ^^^ EGF stimulation of canine epithelial cells induced a rapid and transient association of the SH 3 SH2 SH 3 protein GRB 2 with dynamin , a guanosine triphosphatase that regulates endocytosis . ^^^ Disruption of GRB 2 interactions by microinjection of a peptide corresponding to the GRB 2 SH2 domain or its phosphopeptide ligand blocked EGF receptor endocytosis ; other SH 2 domains that bind EGF receptors or antibodies that neutralize RAS did not . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Cbl was basally associated with the adaptor protein growth factor receptor binding protein 2 ( Grb 2 ) , and this interaction was further enhanced by EGF stimulation ; however , the interaction was entirely mediated via the Grb 2 Src homology 3 ( SH 3 ) domains , suggesting that binding of Grb 2 SH2 domain to EGF receptor provides one mechanism of Cbl ' s association with the EGF receptor . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Surprisingly , however , despite the EGF induced decrease in the amount of Grb 2 SOS bound to Shc , the extent of Grb 2 associated with Shc remained constant , and there was a concomitant increase in the amount of SOS associated with Grb 2 . ^^^ In addition , after the insulin stimulated dissociation of Grb 2 from SOS , EGF treatment induced the reassociation of the Grb2 . ^^^ Together , these data suggest the presence of distinct Grb 2 SOS pools that are independently utilized by insulin and EGF in their recruitment to tyrosine phosphorylated Shc . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
P120cbl , the product of the c cbl proto oncogene , has previously been shown to become tyrosine phosphorylated following EGF stimulation of cells , and to bind constitutively to the SH 3 domain of the adaptor protein Grb 2 . ^^^ Interaction between Grb 2 and p120cbl increases threefold following EGF treatment of cells ; in vitro , this induction of Grb 2 association with unphosphorylated p120cbl can be mimicked by the addition of tyrosine phosphorylated Shc , suggesting a transfer of information between the SH 2 and SH 3 domains of Grb 2 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Western blot analysis of anti PTP1D immune complexes derived from EGF treated cells demonstrated a ligand dependent coupling between the phosphatase and GRB 2 in vivo . ^^^ Importantly , a GST fusion protein containing the PTP1D SH 2 domains was not capable of generating the EGF induced linkage to GRB 2 . ^^^ Additional experiments indicated that neither the binding of the nucleotide exchange factor Sos to GRB 2 nor tyrosine phosphorylation of PTP1D was required for EGF stimulated coupling of PTP1D to GRB 2 . ^^^ This is the first demonstration of a growth factor or cytokine induced coupling of a protein through an SH 3 domain and suggests that GRB 2 functions to target PTP1D , in addition to Sos , to the plasma membrane in response to EGF . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Because Ras activation by EGF involves EGF stimulated association of EGF R with Grb 2 , the EGF R was immunoprecipitated and a Western blot was probed for Grb 2 . ^^^ As expected we found that EGF stimulated an association of EGF R with Grb 2 , PRL , however , blocked this association . ^^^ The studies demonstrate that PRL either directly or indirectly inhibits the ability of EGF to induce EGF R association with Grb 2 , to activate Ras , and to activate and phosphorylate MAPK . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
As in Shc , N Shc can bind activated EGF receptor , become tyrosine phosphorylated , and form a complex with Grb 2 adapter protein following EGF stimulation . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In contrast , EGF stimulation resulted in the predominant co immunoprecipitation of Grb 2 with the EGF receptor , whereas CrkII primarily associated with an unidentified 120 130 kDa protein . ^^^ However , EGF stimulation had no effect on the association state of the Grb 2 SOS or the Nck SOS complexes but did result in a time dependent dissociation of the CrkII from SOS . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
We also show that the truncated EGF receptor constitutively associates with the adapter proteins Shc and Grb 2 which are involved in the recruitment of Ras to activated receptors . ^^^ We conclude that the increased tumorigenic potential of glioblastoma cells expressing the truncated EGF receptor is due at least in part to Ras activation presumably involving the Shc and Grb 2 adapter proteins . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
We therefore compared the effects of CCK and epidermal growth factor ( EGF ) on Tyr phosphorylation of the adaptor proteins Shc and its association with Grb 2 and the guanine nucleotide exchange factor SOS . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Epidermal growth factor ( EGF ) stimulated Ras activation involves specific interactions between the EGF receptor ( EGFR ) , the adaptor proteins Grb 2 and Shc , and the nucleotide exchange factor Sos 1 . ^^^ These results indicate that the binding of Grb 2 to the phosphorylated Tyr 1068 of EGFR is crucial to the EGF induced Ras / mitogen activated protein kinase signaling pathway . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Using epidermal growth factor ( EGF ) receptor , Grb 2 and Sos proteins as an example , we demonstrated the use of the three hybrid system to detect formation of a three component complex , i . e . , the Grb 2 mediated interactions between EGF receptor and Sos . ^^^ We then used the three hybrid system to screen a library with Gal 4 DNA binding domain EGF receptor and Gal 4 activation domain Sos fusion proteins and isolated a plasmid encoding Grb 2 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Therefore , EGF treatment potentially results in the formation of several multimeric signaling complexes , including EGFR Grb 2 mSos1 , EGFR Shc Grb 2 mSos1 , and Shc Grb 2 mSos1 , linking the receptor to activation of the Ras GTPase . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
The association of Shc with GRB 2 by IGF 1 was detected by immunoblot with anti Shc antibody but was hardly visible with antiphosphotyrosine antibody , which was in marked contrast to efficient tyrosine phosphorylation of Shc by EGF . ^^^ Our results strongly suggest that in human skin fibroblasts , which represent a more physiological cell culture : 1 ) IRS 1 , rather than Shc , is the major tyrosine phosphorylated protein binding GRB 2 in initial phase of IGF 1 signaling ; 2 ) mitogenic potency of receptor tyrosine kinases such as IGF 1 receptor and EGF receptor may not be determined solely by the amount of Shc GRB 2 complex or the activity of MAP kinase ; and 3 ) in contrast to previous reports , IGF 1 and EGF receptor signalings are not defective in leprechaunism . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
The RIalpha subunit of protein kinase A ( PKA ) binds to Grb 2 and allows PKA interaction with the activated EGF receptor . ^^^ Finally , the PKAI EGF R association occurs through the binding of RIalpha to the SH 3 domain ( s ) of Grb 2 adaptor protein , thus allowing the recruitment of the PKAI holoenzyme to the activated EGF R . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Cb 1 Grb2 complexes can be recruited to tyrosine phosphorylated epidermal growth factor ( EGF ) receptors through the SH 2 domain of Grb 2 . ^^^ These data suggest that despite the lack of Grb 2 binding sites , D Cbl functions as a negative regulator of receptor tyrosine kinase signaling in the Drosophila eye by a mechanism that involves its association with EGF receptors or other tyrosine kinases . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Coupling of the murine protein tyrosine phosphatase PEST to the epidermal growth factor ( EGF ) receptor through a Src homology 3 ( SH 3 ) domain mediated association with Grb 2 . ^^^ Experiments in EGF receptor expressing cells show that the interaction between MPTP PEST and Grb 2 results in the binding of this complex to activated EGF receptors . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
With this approach , we confirm the previously characterized interaction between Grb 2 and the EGF receptor , and we identify novel partners of the IGF 1 receptor and of the JAK proteins . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Tyrosine phosphorylation of EGF receptor ( EGFR ) , Shc , and phospholipase C gamma 1 ( PLC gamma ) , and growth factor receptor binding protein 2 ( Grb 2 ) coprecipitation with EGFR and Shc were analyzed by Western blotting . ^^^ Grb 2 binding to EGFR was suppressed , but EGF induced Shc tyrosine phosphorylation and Grb 2 association with Shc were not significantly decreased . ^^^ CONCLUSIONS : Long term ethanol feeding suppressed EGF induced receptor autophosphorylation in rat hepatocytes with differential inhibition of downstream signaling processes mediated by PLC gamma , Shc , and Grb 2 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
For EGF induced mitogen activated protein kinase activation in 293T cells , both Shc PTB and SH 2 domains are essential for optimal activation , indicating that a mechanism independent of Grb 2 engagement with Shc may exist . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In the case of polypeptide growth factors such as the epidermal growth factor ( EGF ) and platelet derived growth factor ( PDGF ) , the steps leading to activation of MAPK require the function of the adaptor protein Grb 2 ( growth factor receptor binding protein 2 ) , which can bind either directly or indirectly via its Src homology 2 domain to activated receptor tyrosine kinases . ^^^ A cell permeable mimetic of the EGF receptor Grb 2 binding site has been investigated for its ability to inhibit biological responses stimulated by a variety of growth factors . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Epidermal growth factor ( EGF ) induced autophosphorylation of the EGF receptor results in high affinity binding of the adaptor protein GRB 2 , which serves as a convergence point for multiple signaling pathways . ^^^ Present studies demonstrate that EGF induces the co immunoprecipitation of phospholipase C ( PLC ) gamma 1 with the adaptor protein GRB 2 and the guanine nucleotide exchange factor Sos , but not with the adaptor protein SHC , in WB cells . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Epidermal growth factor ( EGF ) stimulation did not affect the binding of Grb 2 to HPK 1 but induced recruitment of the Grb2 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In addition , Reps 1 has the capacity to form a complex with the SH 3 domains of the adapter proteins Crk and Grb 2 , which may link Reps 1 to an EGF responsive tyrosine kinase . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In serum starved cells this results in EGF receptor autophosphorylation and the recruitment of Grb 2 , Shc and Sos 1 but does not induce a corresponding increase in MAP kinase activity . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
These results indicate that in addition to Grb 2 mediated activation of Ras , PLC gamma 1 mediated DAG production is required for EGF and PDGF induced S phase entry and gene expression , possibly through activation of PKC . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
This effect has been associated with reduced EGF induced EGF receptor ( EGFR ) tyrosine phosphorylation , Grb 2 association , and Ras activation . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
However , TC 45 inhibited the EGF induced association of p52Shc with Grb 2 , which was attributed to the ability of the PTP to recognize specifically p52Shc phosphorylated on Y 239 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In the present study , we found Ang 2 rapidly induced the tyrosine phosphorylation of the epidermal growth factor ( EGF ) receptor and its association with Shc and Grb 2 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In addition , Shc bound to the activated EGF receptor via the PTB domain dominantly interacts with Grb 2 Sos complex and plays a major role in the Ras signaling pathway . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
To explore the applicability of this nondestructive import method to the study of intracellular processes , a 41 kDa GST Grb2SH2 MTS fusion protein containing the Grb 2 SH2 domain was tested for its effect on the epidermal growth factor ( EGF ) stimulated signaling pathway . ^^^ This fusion protein entered cells , formed a complex with phosphorylated EGF receptor ( EGFR ) , and inhibited EGF induced EGFR Grb 2 association and mitogen activated protein kinase activation . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
An anthranyl moiety placed at the N terminus of a phosphotyrosine peptide potentiates the inhibitory effect of this small peptide on the binding of the Grb 2 SH2 domain to the EGF receptor . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Dominant negative forms of SHP 2 had no effect on EGF stimulated interaction of GRB 2 with EGFR or SHC , nor did they influence phosphorylation of SHC and SHC / EGFR association . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In both cases , ErbB 1 coupled to the adaptor protein Shc , but only when activated by EGF was it able to interact with Grb 2 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In all of the tumor cell lines , EGF caused an association between Shc and Grb 2 , another adapter protein linked to cellular ras activation . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In primary cultured hepatocytes stimulated with hepatocyte growth factor ( HGF ) or epidermal growth factor ( EGF ) , GRB 2 linked HGF receptor or EGF receptor , respectively , to Sos which activated the mitogen activated protein kinase ( MAPK ) cascade . ^^^ In the early phase after PH , GRB 2 activated the Ras MAPK cascade by linking HGF receptor , IRS 1 , or EGF receptor to Sos . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
AG 1478 , a tyrphostin selective for the EGF receptor , reduced the activation of MAP kinase , the tyrosine phosphorylation of SHC , the association of Grb 2 with SHC , and the tyrosine phosphorylation of the EGF receptor and p 120 ( cbl ) but did not block the tyrosine phosphorylation of RAFTK . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
This paper describes a specific interaction between the COOH terminal SH 3 domain of Grb 2 and the NH 2 terminal regulatory domain of MEKK 1 in ER 22 cells overexpressing the EGF receptor . ^^^ Transfection of the NH 2 terminal regulatory domain of MEKK 1 specifically inhibits EGF dependent JNK activation indicating that Grb 2 is involved in MEKK 1 activation . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Binding of EGF to its receptor triggers receptor dimerization and autophosphorylation , recruitment of kinase substrates ( signaling enzyme adapter proteins with an SH 2 domain , Grb 2 adapter protein , and Grb 2 SOS complex ) . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Immunoprecipitation / Western blot studies revealed that CCh stimulated tyrosine phosphorylation of the EGF receptor ( EGFr ) and increased co immunoprecipitation of the adapter proteins , Shc and Grb 2 , with the EGFr . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
This correlates with a specific inability to achieve high levels of p 66 ( SHC ) tyrosyl phosphorylation and association of p 66 ( SHC ) with GRB 2 , despite high levels of EGF receptor ( EGFR ) autophosphorylation . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Activation of muscarinic receptors with carbachol was found to inhibit EGF induced signaling , including tyrosine phosphorylation of the adaptor protein Cbl and of the EGF receptor , and complex formation between Shc proteins and the EGF receptor and Grb 2 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In contrast , EGFR truncation did not impair EGF mitogenic signaling , and in c ' 1000 cells EGF was able to stimulate the association of ErbB 2 with GRB 2 and SHC . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
We demonstrate in vivo , that cbl b , like c cbl , is phosphorylated and recruited to the EGFR upon EGF stimulation and both cbl proteins can bind to the Grb 2 adaptor protein . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
The concentrations of EGF for which PI 3 kinase inhibitors block Ras activation induce formation of Shc Grb 2 complexes but not detectable EGF receptor phosphorylation and do not activate PI 3 kinase . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Asterriquinones produced by Aspergillus candidus inhibit binding of the Grb 2 adapter to phosphorylated EGF receptor tyrosine kinase . ^^^ All seven showed inhibitory activity against the binding of a recombinant protein containing the SH 2 protein domain of Grb 2 to the tyrosine phosphorylated form of the EGF receptor tyrosine kinase . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Since Ras activation requires the assembly of a multiprotein complex , we examined the effect of carbachol and EGF on tyrosyl phosphorylation of Shc and its association with Grb 2 and the guanine nucleotide exchange factor Sos . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Here we show that the EGF mediated ERK activation is abolished by loss of Grb 2 , whereas this response is not affected by loss of Shc . ^^^ Conversely , the EGF mediated c Jun N terminal kinase ( JNK ) activation is dependent on Shc , but not Grb 2 . ^^^ These findings strongly support distinct roles for Grb 2 and Shc in controlling ERK and JNK activation after EGF stimulation . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
The tyrphostin AG 1478 , known to inhibit EGF receptor phosphorylation , also inhibited the angiotensin 2 and EGF induced activation of ERK , the phosphorylation of the EGF receptor , and the subsequent association of Shc and Grb 2 . ^^^ Nitric oxide did not affect either EGF receptor phosphorylation or Shc Grb 2 activation induced by either Ang 2 or EGF . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
EGF and NGF strongly activated tyrosine phosphorylation of Shc and caused association of Src homology collagen ( Shc ) with growth factor receptor bound protein 2 ( Grb 2 ) ; however , neither NE nor UTP caused substantial activation of the Shc / Grb2 pathway . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Evidence is also presented that Shp 2 does not appear to modulate the signal relay from EGF receptor to Ras through the Shc , Grb 2 , and Sos proteins . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Of note , IL 8 induced transient phosphorylation of the epidermal growth factor ( EGF ) receptor and its association with the adaptor molecules Shc and Grb 2 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
H2O2 induced the phosphorylation of the EGF receptor and the formation of a receptor complex comprising Shc , Grb 2 , Sos , and the EGF receptor . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
The enhanced activation of EGFR by the tethered form of TGFalpha was reflected by higher activation of Grb 2 , SHC and Erk downstream mediators of EGF receptor signaling . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Coimmunoprecipitation studies demonstrated that both EGF and Cpd 5 induced tyrosine phosphorylation of EGFR was associated with increased amounts of adapter proteins Shc and Grb 2 , and the Ras GTP GDP exchange protein Sos , indicating the formation of functional EGFR complexes . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In the A 549 human adenocarcinoma cell line dexamethasone inhibited epidermal growth factor ( EGF ) stimulated cytosolic PLA ( 2 ) ( cPLA ( 2 ) ) activation and AA release by blocking the recruitment of Grb 2 to the activated EGF receptor ( EGF R ) through a glucocorticoid receptor ( GR ) dependent ( RU 486 sensitive ) , transcription independent ( actinomycin insensitive ) , mechanism . ^^^ The dexamethasone induced block of Grb 2 recruitment was parallelled by changes in phosphorylation status and subcellular localization of lipocortin 1 ( LC 1 ) and an increase in the amount of the tyrosine phosphoprotein co localized with EGF R . ^^^ Our results point to an unsuspected rapid effect of glucocorticoids , mediated by occupation of GR but not by changes in gene transcription , which is brought about by competition between LC 1 and Grb 2 leading to a failure of recruitment off signalling factors to EGF R . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In contrast , LAR selectively inhibited the epidermal growth factor ( EGF ) induced phosphorylation of p130CAS and the formation of the complex between p130CAS and GRB 2 but this effect did not influence the activation of MAPK by EGF . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Recruitment of Gab 1 to Met or epidermal growth factor ( EGF ) receptors requires a receptor binding site for the Grb 2 adapter protein and a proline rich domain in Gab 1 , defined as the Met binding domain . ^^^ The association of Gab 1 with Grb 2 is required for Gab 1 recruitment to the EGF receptor but not the Met receptor . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Using a specific Gab 2 antibody , we demonstrated its expression in and association with p 85 , SHP 2 , and Grb 2 upon EGF treatment of rat hepatocytes . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Grb 2 protein , which is the downstream effector of the EGF receptor , acts as an adaptor protein between the EGF receptor and the Ras guanine nucleotide exchange factor , son of sevenless ( Sos ) protein . ^^^ However , the significance of Grb 2 and Sos proteins , which is related to EGF triggered Ras activation , has not been elucidated in human bladder cancer . ^^^ We examined the expression of EGF receptor , Grb 2 , and Sos proteins in these cells by Western blot analysis . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Grb 2 protein is comprised of one SH 2 surrounded by two SH 3 domains and interacts by means of its Src homology ( SH 2 ) domain with phosphotyrosine residues of target proteins such as the epidermal growth factor ( EGF ) receptor or the Shc adaptor . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Interaction of EGF receptor and grb 2 in living cells visualized by fluorescence resonance energy transfer ( FRET ) microscopy . ^^^ Stimulation by EGF resulted in the recruitment of Grb 2 YFP to cellular compartments that contained EGFR CFP and a large increase in FRET signal amplitude . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
These results show that , in addition to Shc and Grb 2 , a PI3K dependent pathway involving Gab 1 and SHP 2 is essential for Ras activation under EGF stimulation . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
We show that a substantial fraction of tyrosine phosphorylated epidermal growth factor receptor ( EGFR ) and Shc , Grb 2 and Cbl after internalization relocates from early endosomes to compartments which are negative for the early endosomes , recycling vesicle markers EEA 1 and transferrin in EGF stimulated cells . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Specific inhibition of the interaction of ACK 1 with Cdc 42 or Grb 2 by the use of these constructs diminished tyrosine phosphorylation of both ACK 1 and Dbl in response to EGF . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Our results indicate that while there are measurable differences in the abilities of the two mutant receptors to stimulate [ ( 3 ) H ] thymidine incorporation between 20 and 24 h after addition of EGF , these differences can not be correlated with significant differences in EGF stimulated tyrosine phosphorylation of mutant EGF receptor and endogenous ErbB 2 , the extent of receptor internalization , EGF stimulated ion uptake , stimulation of SHC activity , or receptor association with Grb 2 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
The interaction of the activated epidermal growth factor ( EGF ) receptor ( EGFR ) with the Src homology 2 ( SH 2 ) domain of Grb 2 ( growth factor receptor bound protein 2 ) initiates signalling through Ras and mitogen activated protein kinase . ^^^ Stimulation by EGF resulted in the recruitment of Grb 2 YFP and YFP Shc to cellular compartments that contained EGFR CFP , and a large increase in the FRET signal . ^^^ Moreover , in contrast with previous biochemical studies , FRET experiments show that a large pool of Grb 2 and Shc is associated with EGFRs for a prolonged period after EGF stimulation . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In addition to the EGF receptor , PI3K C2beta ( 2 298 ) also isolated both Shc and Grb 2 from A 431 cell lysates . ^^^ Using immobilized , phosphorylated EGF receptor , recombinant PI3K C2beta was only purified in the presence of Grb 2 . ^^^ We conclude that proline rich motifs within the N terminus of PI3K C2beta mediate the association of this enzyme with activated EGF receptor and that this interaction involves the Grb 2 adaptor . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Binding of EGF and PDGF to the receptors activates receptor tyrosine kinase and rapid association of adapter proteins Shc and Grb 2 , and evokes the Ras / MAP kinase cascade . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Two standard Grb 2 interacting sequences , either from the EGF receptor or the ShcA 313Y region , could not replace the requirement for ShcA binding to MT , indicating an enhanced role for the ShcA 239 / 240YY motif . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
We found that Grb 2 was tyrosine phosphorylated in cells expressing BCR / ABL and in A 431 cells stimulated with epidermal growth factor ( EGF ) . ^^^ Phosphorylation of Grb 2 by Bcr / Abl or EGF receptor reduced its SH 3 dependent binding to Sos in vivo , but not its SH 2 dependent binding to Bcr / Abl . ^^^ In vivo expression of a Grb 2 mutant where Tyr 209 was changed to phenylalanine enhanced BCR / ABL induced ERK activation and fibroblast transformation , and potentiated and prolonged Grb 2 mediated activation of Ras , mitogen activated protein kinase and c Jun N terminal kinase in response to EGF stimulation . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Co immunoprecipitation studies show that the associations of NGF or EGF receptors with growth factor receptor binding protein 2 ( Grb 2 ) and phosphoinositide 3 kinase are significantly inhibited . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In support of this hypothesis , overexpression of the EGFR adaptor protein Grb 2 increased cell proliferation and restored EGF induced mitosis . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Surprisingly , EGF and TGF alpha induced full activation of MAPK in duration and intensity and stimulated association of the EGFR with Shc and Grb 2 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Role of Grb 2 in EGF stimulated EGFR internalization . ^^^ To gain insight into the trafficking pathways followed by these molecules after activation by EGF , we visualized Grb 2 and EGFR fused to GFP spectral variants in single live cells . ^^^ Within 1 minute of EGF stimulation , Grb 2 redistributed to the plasma membrane where it bound EGFR CFP in an SH 2 dependent manner . ^^^ YFP tagged Grb 2 containing an inhibitory mutation in either N or C SH 3 domain redistributed to the plasma membrane upon EGF stimulation , but the macropinocytic structures containing Grb 2 YFP and EGFR CFP did not translocate inward and appeared to remain tethered to the plasma membrane . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
We previously found that the HCV nonstructural 5A ( NS5A ) protein interacts with growth factor receptor binding protein 2 ( Grb 2 ) adaptor protein and inhibits the activation of extracellular signal regulated kinases 1 and 2 ( ERK1 / 2 ) by epidermal growth factor ( EGF ) . ^^^ NS5A containing mutations within the C terminal proline rich motif neither bound Grb 2 nor inhibited ERK1 / 2 activation by EGF , demonstrating that NS5A Grb 2 binding and downstream effects were due to direct interactions . ^^^ Interestingly , NS5A could also form a complex with the Grb 2 associated binder 1 ( Gab 1 ) protein in an EGF treatment dependent manner . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Epidermal growth factor ( EGF ) stimulates recruitment of RN tre to the EGF receptor ( EGFR ) in a Grb 2 dependent manner . ^^^ Grb 2 and the EGFR are internalized and co localized in endocytic vesicles in response to EGF . ^^^ Strikingly , RN tre does not block EGF induced internalization of a Grb 2 mutant deficient in RN tre binding . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Overexpression of Odin , but not an unrelated adapter protein , Grb 2 , inhibited EGF induced activation of c Fos promoter . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Grb 2 regulates internalization of EGF receptors through clathrin coated pits . ^^^ Quantitative analysis of colocalization of EGF rhodamine conjugate and coated pits labeled with yellow fluorescent protein tagged beta 2 subunit of clathrin adaptor complex AP 2 revealed that EGFR mutants lacking Grb 2 binding sites do not efficiently enter coated pits . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Immunoblots showed that Grb 2 was co immunoprecipitated with EGFR after EGF stimulation . ^^^ CONCLUSIONS : 1 ) Association of Grb 2 to EGFR in BxPC 3 induced by EGF in the presence of Erbitux indicates an alternate pathway of Ras MAPK activation , which may be related with the tumor resistance to treatment ; 2 ) transactivation of EGFR downstream Ras MAPK pathway by FGF contributes the resistance to treatment ; and 3 ) downregulation of EGFR may increase the response to therapy . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
These growth factors , most notably EGF , trigger cell proliferation via signal transduction pathways involving EGF R , adapter proteins ( Grb 2 , Shc and Sos ) , Ras , Raf 1 and MAP ( Erk1 / Erk2 ) kinases , which , after translocation to nuclei , activate transcription factors and cell proliferation . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Since Ras MAPK and STAT pathways are simultaneously stimulated by EGF , and Tyr 1086 and Tyr 1068 of EGFR are reported to be the binding sites for both Grb 2 and Stat 3 , we investigated the possible regulatory role of Grb 2 in STAT activation . ^^^ In the present study , we report that transient expression of Grb 2 specifically down regulates EGF stimulated tyrosine phosphorylation of Stat 3 , which leads to a repression of Stat 3 transcriptional activity . ^^^ In contrast , depletion of Grb 2 by RNA interference substantially increases Stat 3 tyrosine phosphorylation induced by EGF . ^^^ Taken together , our results demonstrate that , in EGF signalling , Grb 2 regulates Stat 3 activation negatively at the receptor level . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Grb 2 regulation of the actin based cytoskeleton is required for ligand independent EGF receptor mediated oncogenesis . ^^^ Together , these results demonstrate a Ras independent role for Grb 2 in modulating cytoskeletal function during ligand independent EGF receptor mediated transformation , and provide further support for the hypothesis that ligand independent oncogenic signaling is qualitatively distinct from ligand dependent mitogenic signaling by the EGF receptor . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Using this technique , we have studied the process of early signal transduction of epidermal growth factor ( EGF ) in single molecules : binding of EGF to its receptor ( EGFR ) on the cell surface , dimerization of EGFR induced by binding of EGF , fluctuation of the structure of EGFR clusters , activation of EGFR through tyrosine phosphorylations on its cytoplasmic domain , and recognition of activated EGFR by a cytoplasmic adaptor protein , Grb 2 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
These proteins contain a set of sequences providing interactions with a wide range of receptor and nonreceptor tyrosine kinases and signaling proteins with SH 2 and SH 3 domains ( for example , EGF and PDGF receptors , Src kinases , PI 3 kinase p 85 , Crk , GRB 2 , Vav , etc . ) . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Ligand binding causes the EGF receptor ( EGFR ) to become ubiquitinated by Cbl upon association with the adaptor protein Grb 2 . ^^^ Incubation of cells with EGF on ice caused translocation of Grb 2 and Cbl from the cytosol to the rim of coated pits . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In addition to interactions with multiple signaling adaptors Grb 2 , SHC , SCK , and NSP 2 , EGF receptors in HN 5 cells were shown to form direct or indirect physical interactions with additional kinases including ACK 1 , focal adhesion kinase ( FAK ) , Pyk 2 , Yes , EphA 2 , and EphB 4 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Analysis of detergent resistant membrane fractions revealed that the EGF dependent association of endocytic proteins with rafts is as efficient as that of signaling effector molecules , such as Grb 2 or Shc . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
It was shown that , following EGF stimulation , these cells exhibited decreased EGF receptor tyrosine phosphorylation , aberrant recruitment of the adaptor proteins ShcA and Grb 2 to the EGF receptor , reduced phosphorylation of ShcA and reduced Ras activation in comparison with control cells . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
The association of Grb 2 with PLC gamma 1 was induced by the treatment with epidermal growth factor ( EGF ) . ^^^ Replacement of Tyr 783 with Phe completely blocked EGF induced interaction of PLC gamma 1 with Grb 2 , indicating that tyrosine phosphorylation of PLC gamma 1 at Tyr 783 is essential for the interaction with Grb 2 . ^^^ Interestingly , the depletion of Grb 2 from HEK 293 cells by RNA interference significantly enhanced increased EGF induced PLC gamma 1 enzymatic activity and mobilization of the intracellular Ca2+ , while it did not affect EGF induced tyrosine phosphorylation of PLC gamma 1 . ^^^ Taken together , these results suggest Grb 2 , in addition to its key function in signaling through Ras , may have a negatively regulatory role on EGF induced PLC gamma 1 activation . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
The model includes EGF , EGFR , the adapter proteins Grb 2 and Shc , and the guanine nucleotide exchange factor Sos , which is activated through EGF induced formation of EGFR Grb 2 Sos and EGFR Shc Grb 2 Sos assemblies at the plasma membrane . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Activation of the epidermal growth factor ( EGF ) receptor induces formation of EGF receptor and Grb 2 containing clathrin coated pits . ^^^ These contained EGF , EGFR , clathrin , and Grb 2 but not the TfR . ^^^ Overexpression of Grb 2 with inactivating point mutations in N or C terminal SH 3 domains or in both SH 3 domains inhibited EGF induced formation of coated pits efficiently , even though Grb 2 SH3 mutations did not block activation of mitogen activated protein kinase ( MAPK ) or phosphatidylinositol 3 kinase ( PI3K ) . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Here we show results of single molecule observations of the association and dissociation between phosphorylated EGF receptors and Cy 3 labeled growth factor receptor binding protein 2 ( Grb 2 ) proteins in A 431 cells stimulated by the immobilized EGF and discuss the utility of this method for the study of intracellular signal transduction . . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
Nucleotide exchange stimulation by PE is prevented by PKC ( protein kinase C ) inhibition but not by EGFR [ EGF ( epidermal growth factor ) receptor ] blockade , despite the fact that EGFR inhibition aborts basal and PE induced Shc ( Src homology and collagen homology ) phosphorylation and Shc Grb 2 ( growth factor receptor bound protein 2 ) association . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
In this report , we demonstrate that class 2 phosphoinositide 3 kinase C2beta ( PI3KC2beta ) associates with the Eps8 / Abi1 / Sos1 complex and is recruited to the EGF receptor as part of a multiprotein signaling complex also involving Shc and Grb 2 . ^^^
Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P01133 and P62993	Pubmed	SVM Score :0.0
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