| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.92632498 |
| We now report that plating cells on fibronectin triggers association of Grb 2 with c Abl , suggesting possible involvement of c Abl with integrin activation of the MAP kinase pathway . 0.92632498^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| It has been shown that the SH 2 containing adapter protein Grb 2 binds to the autophosphorylation site Tyr ( p ) 177 whereby it couples Bcr Abl to the Ras pathway . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| The Bcr / Abl fusion protein is a constitutively active tyrosine kinase that stimulates several intracellular signaling pathways , including activation of Ras through direct binding of the SH 2 containing adapter protein Grb 2 to Bcr tyrosine 177 . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| In contrast , Grb 2 , Crk , Abl , p 85 phosphatidylinositol 3 kinase , and GTPase activating protein SH 2 domains showed lower or no binding to Fyn or Lck SH 3 domains . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| We demonstrate that the K protein contains a cluster of at least three SH 3 binding sites ( P 1 , PPGRGGRPMPPSRR , amino acids 265 278 ; P 2 , PRRGPPPPPPGRG , 285 297 ; and P 3 , RARNLPLPPPPPPRGG , 303 318 ) and that each one of these sites is capable of selectively engaging c Src and Vav SH 3 domains but not SH 3 domains of Abl , p 85 phosphatidylinositol 3 kinase , Grb 2 , and Csk . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| Immunoprecipitation analysis revealed a stable complex of GRB 2 and 230 kDa BCR / ABL proteins , indicating that the Ras activation pathway is involved in the process of transformation . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| Here we show that Shc is tyrosine phosphorylated and associates with Grb 2 in 5 Abl transformed cells , whereas Shc in NIH3T3 cells is phosphorylated solely on serine and is not Grb 2 associated . ^^^ The unique non phosphotyrosine mediated binding of Shc may allow direct tyrosine phosphorylation of Shc by 5 Abl and subsequent activation of the Ras pathway through assembly of a signaling complex with Grb 2 mSos . . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| Here we report the synthesis and solution structure of the amino terminal SH 3 domain of GRB 2 and of its more stable Ser 32 mutant . 1H NMR analysis of the complex between the Ser 32 GRB 2 N SH 3 domain and the proline rich peptide VPPPVPPRRR , derived from h Sos , shows that relative to the SH 3 peptide complexes described for PI3K , Fyn and Abl , the proline rich peptide in this complex binds in the opposite orientation . . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| In bcr abl transformed cells , Grb 2 and mSos 1 formed a physical complex with Bcr Abl . ^^^ In vitro , the Grb 2 SH2 domain bound Bcr Abl through recognition of a tyrosine phosphorylation site within the amino terminal bcr encoded sequence ( p . ^^^ These results suggest that autophosphorylation within the Bcr element of Bcr Abl creates a direct physical link to Grb 2 mSos1 , and potentially to the Ras pathway , and thereby modifies the target specificity of the Abl tyrosine kinase . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| Selective binding to a subset of 15 different recombinant SH 3 domains occurs through proline rich sequence motifs similar to those that mediate the interaction of the SH 3 domains of Grb 2 and Abl proteins to the guanine nucleotide exchange protein , Sos , and to the 3BP1 protein , respectively . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| Activation of Erk 1 by oncogenic Abl was effectively inhibited by Grb 2 with mutations in either its SH 2 or SH 3 domain or by Crk 1 with an SH 3 domain mutation . ^^^ These results suggest that both Crk and Grb 2 may contribute to the activation of Erk by oncogenic Abl , whereas Nck is unlikely to participate in this pathway . ^^^ This finding suggests that in Abl transformed cells , more than one class of tyrosine phosphorylated sites ( those that bind the Grb 2 SH2 domain and those that bind the Crk SH 2 domain ) can lead to Ras activation . ^^^ 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 . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| The SH 2 domains of PLC gamma Nterm . , Nck , Grb 2 , GAP and Abl have been model built with high affinity phosphopeptides fitted into the putative binding sites . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| In BCR ABL delta 1 40 reactivated by the SH 3 deletion , transphosphoryation of other cellular proteins like p 62 or SHC in vivo and autophosphorylation with recruitment of GRB 2 were also recovered . . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| Distinct ligand preferences of Src homology 3 domains from Src , Yes , Abl , Cortactin , p53bp2 , PLCgamma , Crk , and Grb 2 . ^^^ Specifically , we have found that the Src SH 3 domain selects peptides sharing the consensus motif LXXRPLPXpsiP , whereas Yes SH 3 selects psiXXRPLPXLP , Abl SH 3 selects PPXthetaXPPPpsiP , Cortactin SH 3 selects +PPpsiPXKPXWL , p53bp2 SH 3 selects RPXpsiPpsiR+SXP , PLCgamma SH 3 selects PPVPPRPXXTL , Crk N terminal SH 3 selects psiPpsiLPpsiK , and Grb 2 N terminal SH 3 selects +thetaDXPLPXLP ( where psi , theta , and + represent aliphatic , aromatic , and basic residues , respectively ) . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : The 5 abl oncogene of the Abelson murine leukemia virus ( A MuLV ) encodes a cytoplasmic tyrosine kinase that can associate with phosphoinositide 3 kinase , Shc and Grb 2 , and activate the pathway that leads from Ras to mitogen activated protein ( MAP ) kinase . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| Expression of BCR / abl containing a mutation ( Y177F ) that prevents its interaction with GRB 2 led to a decrease in the phosphorylation of Stat 1 and Stat 5 . ^^^ This suggested that GRB 2 , or its binding site on BCR / abl , may participate in the phosphorylation of Stat proteins . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| To elucidate the structural requirement of BCR ABL for the interactions with SH 2 containing signaling molecules , we examined a series of BCR ABL mutants which include the Grb 2 binding site deleted BCR ABL ( 1 63 BCR / ABL ) , the tetramerization domain deleted BCR ABL ( 64 509 BCR / ABL ) , and the SH 2 domain deleted BCR ABL ( BCR / ABL deltaSH 2 ) . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| In addition , the c Abl SH 3 domain binds Grb IR / Grb10 , whereas Fyn , phosphatidylinositol 3 kinase p 85 , and Grb 2 SH3 domains do not . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| Our experiments show that , in contrast to other cell types , the in vivo interaction of cbl with GRB 2 and p 85 is significantly enhanced in BCR / abl transformed BaF 3 cells and that tyrosine phosphorylation of cbl leads to a direct interaction with GRB 2 , p 85 and abl SH 2 domains . ^^^ Although the interaction of cbl with GRB 2 in transformed cells was facilitated by binding of GRB 2 to BCR / abl , phosphorylation of cbl and its interaction with p 190 BCR / abl remained unaltered in BaF 3 cells transformed by p190Y177F BCR / abl mutant which is unable to bind GRB 2 . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| We and others have shown that the Bcr Abl oncoprotein binds activators of the Ras pathway such as Grb 2 and Shc . ^^^ We performed experiments to determine whether Bcr , which was tyrosine phosphorylated within cells by activated c Abl , could also bind Grb 2 , and whether phosphotyrosine 177 was the major binding site . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| To elucidate the structural requirement of BCR ABL for the interactions with SH 2 containing signaling molecules , we examined a series of BCR ABL mutants which include the Grb 2 binding site deleted BCR ABL ( 1 63 BCR / ABL ) , the tetramerization domain deleted BCR ABL ( 64 509 BCR / ABL ) , and the SH 2 domain deleted BCR ABL ( BCR / ABL delta SH 2 ) . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
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: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| The Src family kinase Hck interacts with Bcr Abl by a kinase independent mechanism and phosphorylates the Grb 2 binding site of Bcr . bcr abl , the oncogene causing chronic myeloid leukemia , encodes a fusion protein with constitutively active tyrosine kinase and transforming capacity in hematopoietic cells . ^^^ Finally , experiments with a series of kinase negative Bcr Abl mutants showed that Hck phosphorylated Bcr Abl and induced the binding of Grb 2 to Tyr 177 of Bcr Abl . ^^^ This physical interaction stimulates the Hck tyrosine kinase , which may then phosphorylate the Grb 2 binding site in Bcr Abl . . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| In contrast to a second TEL / ABL fusion ( type B ) identified in two cases of myeloid leukaemia , the portion of TEL contained in the type A TEL / ABL fusion was smaller and did not contain a potential Grb 2 binding site . ^^^ Our results support the conclusion that the protein interaction domain of BCR and TEL , but not the Grb 2 binding site , are the important functional components in the activation of ABL kinase in haemopoietic discase . . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| Tyrosine phosphorylation of Bcr by Fes greatly enhanced the binding of Bcr to the SH 2 domains of multiple signalling molecules in vitro , including Grb 2 , Ras GTPase activating protein , phospholipase C gamma , the 85 , 000 M ( r ) subunit of phosphatidylinositol 3 ' kinase , and the Abl tyrosine kinase . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| A proline rich fragment of the NR2D subunit ( 2D ( 866 1064 ) ) bound to the Abl SH 3 domain but not to the SH 3 domains from Src , Fyn , Grb 2 , GAP , or phospholipase C gamma ( PLCgamma ) . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| The downregulation of Abl tyrosine kinase activity was not influenced by mutation or deletion of SH 2 or SH 3 domains or mutation of the GRB 2 binding site . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| Phosphorylated CD 19 recruits other effector molecules including Vav , Grb 2 , phosphoinositide 3 kinase , phospholipase Cgamma 2 , and c Abl , which may contribute to CD 19 regulation of B cell function . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| Tyrosine phosphorylation of Grb 2 by Bcr / Abl and epidermal growth factor receptor : a novel regulatory mechanism for tyrosine kinase signaling . ^^^ Growth factor receptor binding protein 2 ( Grb 2 ) plays a key role in signal transduction initiated by Bcr / Abl oncoproteins and growth factors , functioning as an adaptor protein through its Src homology 2 and 3 ( SH 2 and SH 3 ) domains . ^^^ 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 . ^^^ |
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| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| The autophosphorylation site tyrosine 177 binds the adaptor Grb 2 and helps determine the lineage and severity of BCR / ABL disease : Tyr 177 mutation ( BCR / ABL Y177F ) dramatically impairs myeloid leukemogenesis , while diminishing lymphoid leukemogenesis . ^^^ |
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| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NF kappaB / Rel transactivation was dependent on abl kinase activity but independent of Grb 2 and Grb 10 binding tobcr sequences . ^^^ |
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| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| Bcr Abl did , however , associate with Grb 2 , an adaptor protein that binds tyrosine 177 of Bcr Abl . ^^^ In a yeast three hybrid assay , Grb 2 mediated an interaction between Cbl and Bcr Abl that was dependent on a functional Grb 2 binding site . ^^^ In cells expressing Bcr Abl with a mutation in the Grb 2 binding site , binding of Cbl to Bcr Abl was significantly reduced , but Cbl tyrosine phosphorylation was maintained . ^^^ Grb 2 or another , yet unidentified , protein may mediate an initial interaction between Cbl and Bcr Abl that is independent of Cbl tyrosine phosphorylation . ^^^ |
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| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| A direct binding site for Grb 2 contributes to transformation and leukemogenesis by the Tel Abl ( ETV 6 Abl ) tyrosine kinase . ^^^ A direct binding site for the Grb 2 adapter protein is required for the induction of fatal chronic myeloid leukemia ( CML ) like disease in mice by Bcr Abl . ^^^ Here , we demonstrate direct binding of Grb 2 to the Tel Abl ( ETV 6 Abl ) fusion protein , the product of complex ( 9 ; 12 ) chromosomal translocations in human leukemia , via tyrosine 314 encoded by TEL exon 5 . ^^^ A Tel Abl point mutant ( Y314F ) and a splice variant without TEL exon 5 sequences ( Deltae 5 ) lacked Grb 2 interaction and exhibited decreased binding and phosphorylation of the scaffolding protein Gab 2 and impaired activation of phosphatidylinositol 3 kinase , Akt , and extracellular signal regulated kinase / mitogen activated protein kinase in hematopoietic cells . ^^^ Lack of the Grb 2 binding site had no effect on development of small bowel syndrome but significantly attenuated the induction of CML like disease by Tel Abl . ^^^ |
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| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| The interaction between p85alpha SH 3 and BCR / ABL may be intermediated by proteins such as c Cbl , Shc , Grb 2 , and / or Gab 2 . ^^^ |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P62993 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|