Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Utilizing unique phospho specific antibodies generated against various tyrosines of c Met , we show that Y 1003 ( binding site for c Cbl and a negative regulatory site ) , Y 1313 ( binding site for PI3K ) , Y1230 / Y1234 / Y1235 ( autophosphorylation site ) , Y 1349 ( binding site for Grb 2 ) , Y 1365 ( important in cell morphogenesis ) are phosphorylated in response to HGF ( 40 ng / ml , 7 . 5 min ) in H 69 cells . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Coupling of Gab 1 to c Met , Grb 2 , and Shp 2 mediates biological responses . ^^^ We have now mapped the c Met and Grb 2 interaction sites using reverse yeast two hybrid technology . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Mutation of tyrosine 489 to phenylalanine does not affect the exogenous kinase activity of the Tpr Met oncoprotein toward casein , but it impairs the ability of the mutant protein to bind to and activate phosphatidylinositol 3 kinase in vivo and completely abolishes the in vivo association with the Grb 2 adaptor protein as well as the association and / or phosphorylation of an unknown protein of 110 kDa . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
HGF stimulated Gab 1 association with c Met , Grb 2 , SHP 2 , PI3K , Shc , Crk isoforms and CrkL , but not with PLCgamma 1 . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Association of the multisubstrate docking protein Gab 1 with the hepatocyte growth factor receptor requires a functional Grb 2 binding site involving tyrosine 1356 . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
After stimulation of the HGF receptor , Shc is phosphorylated on Y317VNV , generating an high affinity binding site for Grb 2 ( Kd = 15 nM ) . ^^^ This duplicates the high affinity binding site for Grb 2 present on the HGF receptor ( Y1356VNV ) . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Immunoprecipitation was performed with antisera to signal transducers and activators of transcription 1 ( STAT 1 ) , STAT 3 , Janus kinase 1 ( Jak 1 ) , Shc , Grb 2 , Sos 1 , and HGF receptor ( met ) . ^^^ Phosphorylated HGF receptor coimmunoprecipitated with Shc , Grb 2 , and Sos 1 . ^^^
Interacting proteins: P08581 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: P08581 and P62993	Pubmed	SVM Score :0.0
The HGF receptor directly activates PI 3 kinase , Ras and STAT signalling pathways and phosphorylates the adaptator GRB 2 Associated Binder 1 ( Gab 1 ) . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Pathways downstream of Shc and Grb 2 are required for cell transformation by the tpr Met oncoprotein . ^^^ We have previously demonstrated that a single tyrosine residue in the carboxyl terminus , Tyr 489 , is highly phosphorylated and is essential for efficient transformation of Fr3T3 fibroblasts by Tpr Met and for the association of Tpr Met with the Grb 2 adaptor protein and phosphatidylinositol 3 ' kinase . ^^^ To distinguish which of these substrates are required for cell transformation by the Tpr Met oncoprotein , we generated a novel Tpr Met mutant that selectively fails to associate with the Grb 2 adaptor protein . ^^^ Utilizing this mutant , together with additional Tpr Met mutants containing Tyr to Phe substitutions , we have demonstrated that transformation of Fr3T3 fibroblasts by the Tpr Met oncoprotein is dependent upon pathways downstream of Shc and Grb 2 and that pathways downstream of phosphatidylinositol 3 ' kinase , phospholipase Cgamma , and SHPTP2 / Syp are insufficient for transformation . . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Specific uncoupling of GRB 2 from the Met receptor . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Branching tubulogenesis but not scatter of madin darby canine kidney cells requires a functional Grb 2 binding site in the Met receptor tyrosine kinase . ^^^ Cells expressing this mutant receptor scattered but were unable to form branching tubules , indicating that a Grb 2 binding site in the Met receptor is critical for morphogenic responses . . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Uncoupling of Grb 2 from the Met receptor in vivo reveals complex roles in muscle development . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Regulation of the urokinase type plasminogen activator gene by the oncogene Tpr Met involves GRB 2 . ^^^ Mutation of Y 1356 , which abrogates GRB 2 binding , reduced the induction to half of the control level , while mutation of Y 1349 showed little effect on uPA induction , suggesting an important but partly replaceable role for GRB 2 in Met dependent uPA gene induction . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
The resultant chimeric p 65 ( Tpr Met ) protein is constitutively phosphorylated on tyrosine residues in vivo and associates with a number of SH 2 containing signaling molecules including the p 85 subunit of PI 3 kinase and the Grb 2 adaptor protein , which couples receptor tyrosine kinases to the Ras signaling pathway . ^^^ Mutation of the binding site for Grb 2 impairs the ability of Tpr Met oncoprotein to transform fibroblasts , suggesting that the activation of the Ras / MAP kinase signaling pathway through Grb 2 may be essential for cellular transformation . ^^^ To test this hypothesis dominant negative mutants of Grb 2 with deletions of the SH 3 domains were introduced into Tpr Met transformed fibroblasts . ^^^ Surprisingly , the Grb 2 mutants blocked activation of the JNK / SAPK but not MAP kinase activity induced by the Tpr Met oncoprotein . ^^^ Additionally , cells expressing dominant negative Grb 2 mutants had reduced PI 3 kinase activity and dominant negative mutants of Rac 1 blocked both Tpr Met induced transformation and activation of JNK . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Efficient cellular transformation by the Met oncoprotein requires a functional Grb 2 binding site and correlates with phosphorylation of the Grb 2 associated proteins , Cbl and Gab 1 . ^^^ We have previously demonstrated that a single carboxyl terminal tyrosine residue , Tyr 489 , is essential for efficient transformation of Fr3T3 fibroblasts by Tpr Met and forms a multisubstrate binding site for Grb 2 , phosphatidylinositol 3 ' kinase , phospholipase Cgamma , SHP 2 , and an unknown protein of 110 kDa . ^^^ A mutant Tpr Met protein that selectively fails to bind Grb 2 has reduced transforming activity , implicating pathways downstream of Grb 2 in Tpr Met mediated cell transformation . ^^^ We show here that the 110 kDa Tpr Met substrate corresponds to the recently identified Grb 2 associated protein , Gab 1 . ^^^ Moreover , we show that tyrosine phosphorylation of the Cbl protooncogene product as well as Gab 1 required Tyr 489 and correlated with the ability of Tpr Met to associate with Grb 2 and to transform cells , providing evidence that pathways downstream of Gab 1 and / or Cbl may play a role in Tpr Met mediated cell transformation . . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
We also show that Tpr Met is much more dependent on its Grb 2 binding site for biological activity than are the other oncogenic forms of the Met receptor . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Concomitant activation of pathways downstream of Grb 2 and PI 3 kinase is required for MET mediated metastasis . ^^^ We previously showed that a Met mutant designed to obtain preferential coupling with Grb 2 ( Met2xGrb2 ) is permissive for motility , increases transformation , but surprisingly is impaired in causing invasion and metastasis . ^^^ In this work we used Met mutants optimized for binding either p 85 alone ( Met2xPI3K ) or p 85 and Grb 2 ( MetPI3K / Grb2 ) to evaluate the relative importance of Ras and PI 3 kinase as downstream effectors of Met . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Induction of the urokinase promoter by HGF / SF via the Met receptor was blocked by co expression of a dominant negative Grb 2 and Sos 1 expression construct . ^^^
Interacting proteins: P08581 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 . ^^^ One corresponds to a canonical Grb 2 binding motif , whereas the second , located within the Gab 1 Met binding domain , requires the proline and arginine residues of an atypical PXXXR motif . ^^^ 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: P08581 and P62993	Pubmed	SVM Score :0.0
We have generated variant forms of the Tpr Met oncoprotein with the ability to bind individually to the p 85 subunit of PI3 ' K , PLCgamma , or to the Grb 2 or Shc adaptor proteins . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Complementation in trans with another nonmetastatic mutant ( N 1358 > H ) , recruiting all the transducers downstream to Met except Grb 2 , rescued the invasive metastatic phenotype . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
By using a mild signaling mutant of Met , we have demonstrated previously that Met requires signaling via the adapter molecule Grb 2 to induce proliferation of myoblasts . ^^^ In contrast , the actions of HGF on sensory neurons are mediated by Met effectors distinct from Grb 2 . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Gab 1 coupling to the HGF / Met receptor multifunctional docking site requires binding of Grb 2 and correlates with the transforming potential . ^^^ It has recently been shown that the Met receptor interacts with Gab 1 , an IRS like adaptor protein , via the docking site ( Y1349VHVNATY1356VNV ) known to bind Grb 2 and multiple SH 2 containing signal transducers . ^^^ These data indicate that Gab 1 coupling to the Met receptor requires binding of Grb 2 and correlates with the transforming potential of Tpr Met . . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
MUC 20 suppresses the hepatocyte growth factor induced Grb 2 Ras pathway by binding to a multifunctional docking site of met . ^^^ We demonstrate here that the C terminus of MUC 20 associates with the multifunctional docking site of Met without ligand activation , preventing Grb 2 recruitment to Met and thus attenuating hepatocyte growth factor ( HGF ) induced transient extracellular signal regulated kinase 1 and 2 activation . ^^^ Taken together , these results suggest that MUC 20 is a novel regulator of the Met signaling cascade which has a role in suppression of the Grb 2 Ras pathway . . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Preferential binding of Grb 2 or phosphatidylinositol 3 kinase to the met receptor has opposite effects on HGF induced myoblast proliferation . ^^^ In this study , we define the role of these effectors in response to HGF by utilizing Met mutants , designed to obtain preferential coupling of Met to either Grb 2 or PI3K or both . ^^^ Taken together , these data suggest that coupling of Met with Grb 2 is necessary for HGF mediated inhibition of muscle differentiation . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
We show that Gab 2 recruitment to the Met receptor is dependent on the Grb 2 adapter protein . ^^^ In contrast , Gab 1 recruitment to Met is both Grb 2 dependent and Grb 2 independent . ^^^ We propose that the Grb 2 independent recruitment of Gab proteins to Met is necessary but not sufficient to promote epithelial morphogenesis . . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
To study the role of HGF and Met in the cerebellum in vivo , we produced a viable hypomorphic Met mutant by knocking in the met locus a point mutation to abrogate the receptor Grb 2 binding site . ^^^ In the knock in presented here Neo was Loxed and excised by Cre recombinase , which led to higher tissue levels of Met ( grb 2 ) protein , sufficient to rescue viability . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Nutrient values differed between years for ash , DE , Mn , Zn , Cys ( P < 0 . 10 ) , Fat , TDN , ME , Met , Ile ( P < 0 . 05 ) , Ca , P , K , Mg , and Cu ( P < 0 . 01 ) . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Grb 2 independent recruitment of Gab 1 requires the C terminal lobe and structural integrity of the Met receptor kinase domain . ^^^ In addition , Gab 1 interacts with the Met / hepatocyte growth factor receptor in a Grb 2 independent manner . ^^^ Alternatively , the structural integrity of the Met receptor , and residues upstream of Tyr 1349 located in the C terminal lobe of the kinase domain , are required for Grb 2 independent interaction with the Gab 1 MBD . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Oncogenic Met receptor induces cell cycle progression in Xenopus oocytes independent of direct Grb 2 and Shc binding or Mos synthesis , but requires phosphatidylinositol 3 kinase and Raf signaling . ^^^ We show that cell cycle progression and activation of MAPK and JNK mediated by the oncogenic Met receptor , Tpr Met , are dependent on its kinase activity and the presence of the twin phosphotyrosine ( Y 482 & Y 489 ) residues in its C terminus , but that the recruitment of Grb 2 and Shc adaptor proteins is dispensable , implicating other signaling molecules . ^^^ However , using Met receptor oncoproteins engineered to recruit specific signaling proteins , we demonstrate that recruitment of Grb 2 or Shc adaptor proteins is sufficient to induce cell cycle progression and activation of MAPK and JNK , while the binding of phospholipase Cgamma or phosphatidylinositol 3 kinase alone fails to elicit these responses . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
Using variant forms of Tpr Met that are engineered to recruit a specific signaling molecule of choice , we demonstrate that the sole recruitment of either the Grb 2 or the Shc adaptor protein is sufficient to induce ectopic structures and anterior reduction , while the recruitment of PI 3Kinase ( PI 3K ) is necessary but not sufficient for this effect . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
We have shown previously that either Grb 2 or Shc mediated signaling from the oncogenic Met receptor Tpr Met is sufficient to trigger cell cycle progression in Xenopus oocytes . ^^^ In this study , we show that overexpression of Grb 2 associated binder 1 ( Gab 1 ) promotes cell cycle progression when Tpr Met is expressed at suboptimal levels . ^^^ This response requires that Gab 1 possess an intact Met binding motif , the pleckstrin homology domain , and the binding sites for phosphatidylinositol 3 kinase and tyrosine phosphatase SHP 2 , but not the Grb 2 and CrkII / phospholipase Cgamma binding sites . ^^^
Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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Interacting proteins: P08581 and P62993	Pubmed	SVM Score :0.0
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