| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.75620436 |
| Bcr phosphorylated on tyrosine 177 binds Grb 2 . 0.75620436^^^ These results indicate that the Bcr protein when phosphorylated at tyrosine 177 binds Grb 2 , thereby implicating Bcr as a potantial activator of the Ras pathway . . 0.71676089^^^ Wild type Bcr and Bcr Y177F were examined under these conditions for their ability to co precipitate with Grb 2 . 0.59106703^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :1.1014987 |
| Upon activation via the B cell receptor ( BCR ) , LAB was phosphorylated and interacted with the adaptor protein Grb 2 . 1.1014987^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.81967569 |
| Upon BCR cross linking , LIME was tyrosine phosphorylated by Lyn and associated with Lyn , Grb 2 , PLC gamma 2 , and PI3K . 0.81967569^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| The analysis of Grb2 / c Cbl interaction demonstrated that , in both acute leukemia and CML blasts , c Cbl was stably complexed with the N terminal Src homology ( SH ) 3 domain of Grb 2 and , in blasts from ALL patients , with the Grb 2 SH2 domain . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
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: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| Shc protein is tyrosine phosphorylated upon B cell receptor ( BCR ) activation and after its phosphorylation interacts with the adaptor protein Grb 2 . ^^^ Tyrosine phosphorylation of Shc and its association with Grb 2 were profoundly reduced in both Lyn and Syk deficient B cells upon BCR stimulation . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
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: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| Single point mutations in the Src homology 2 ( SH 2 ) domain , the major tyrosine autophosphorylation site of the kinase domain , and the Grb 2 binding site in the Bcr region impaired the transformation of fibroblasts by Bcr Abl . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| BCR ABL induced oncogenesis is mediated by direct interaction with the SH 2 domain of the GRB 2 adaptor protein . ^^^ We demonstrate that BCR ABL exists in a complex with GRB 2 in vivo . ^^^ Binding of GRB 2 to BCR ABL is mediated by the direct interaction of the GRB 2 SH 2 domain with a phosphorylated tyrosine , Y 177 , within the BCR first exon . ^^^ The BCR ABL GRB 2 interaction is required for activation of the Ras signaling pathway . ^^^ Mutation of Y 177 to phenylalanine ( Y177F ) abolishes GRB 2 binding and abrogates BCR ABL induced Ras activation . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| In BCR ABL delta 1 40 reactivated by the SH 3 deletion , transphosphoryation of other cellular proteins like p 62 or SHC in vivo and autophosphorylation with recruitment of GRB 2 were also recovered . . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| The BCR activates Ras , presumably by the formation of a Shc Grb 2 adaptor complex , which recruits the Grb 2 associated guanine nucleotide exchange factor Sos to the plasma membrane . ^^^ In order to reveal additional BCR induced signaling events involving the Grb 2 adaptor , we undertook the isolation of Grb 2 binding proteins . ^^^ Instead , Vav was found to inducibly associate with the Grb 2 related adaptor protein Crk upon BCR stimulation . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| The Grb 2 binding to GST / Bcr Abl ( Delta 1 160 ) was 50 % reduced in Rat 1 cells and undetectable in Ba / F3 cells . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| B cell antigen receptor ( BCR ) stimulation induces tyrosine phosphorylation of the Shc adaptor protein and its association with Grb 2 . ^^^ Cbl constitutively interacts with the SH 3 domains of Grb 2 , with a preference for the amino terminal domain , and is in this way recruited to Shc upon BCR stimulation . ^^^ Immunodepletion studies showed that Grb 2 associated Cbl can be phosphorylated by BCR induced tyrosine kinases independent of a Shc / Grb2 interaction . ^^^ This indicates that the BCR can also couple to a Grb 2 complex without the involvement of Shc . ^^^ In contrast to its constitutive interaction with Grb 2 , tyrosine phosphorylated Cbl only associates with Crk after BCR stimulation . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| Strikingly , the assembly of Grb 2 complexes that may couple the BCR to p 21 ( ras ) was clearly altered by the CD 19 bispecific antibody . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| Tyrosine phosphorylation led to the association of BCR with the RAS guanine nucleotide exchange complex GRB 2 SOS in vivo via the GRB 2 SH2 domain , linking BCR to RAS signaling ( Maru , Y . , Peters , K . ^^^ Mutagenesis of BCR Tyr 177 to Phe completely abolished FES induced BCR binding to the GRB 2 SH2 domain , identifying Tyr 177 as an additional phosphorylation site for FES . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| BCR mediated Shc phosphorylation and recruitment of Grb 2 depended on CD 45 expression . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| APS bound to Shc irrespective of stimulation and bound to Grb 2 after stimulation , suggesting that it plays a role in linkage from BCR to Shc / Grb2 pathway . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
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: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| 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: P11274 and P62993 |
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 . ^^^ A Tyr 177 mutated Bcr Abl which lacks the ability to interact with the Grb 2 SH2 domain still transforms myeloid cells and generates tumors in nude mice . ^^^ Among them we confirmed molecules already shown by others to interact with Bcr Abl , in vivo , including Grb 2 , PI 3 kinase and Crk indicating that dimerization in yeast leads to autophosphorylation of tyrosine residues crucial for Bcr Abl signaling in vivo . ^^^ Mutational analysis uncovered a new SH 2 binding site in Bcr Abl located between Bcr aa 242 446 , which is different from the Grb 2 binding site . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| Here we demonstrate that the BCR induced ERK activation is reduced by loss of Grb 2 or expression of a dominant negative form of Ras , RasN 17 , whereas this response is not affected by loss of Shc . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| Here , we report that cross linking of the BCR induces association between Grb 2 and SHIP as well as association between Shc and SHIP . ^^^ Shc and Grb 2 may help to localize SHIP to the cell membrane , regulating SHIP ' s inhibitory function following BCR stimulation . . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| Previous work in our laboratory established that Bcr is a major transformation related substrate for the 5 Fps tyrosine kinase , and tyrosine phosphorylation of Bcr induces Bcr Grb 2 / SOS association in vivo through the Src homology 2 ( SH 2 ) domain of Grb 2 . ^^^ 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: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| Tyrosine phosphorylation of Shc in response to B cell Ag receptor ( BCR ) engagement creates binding sites for the Src homology 2 ( SH 2 ) domain of Grb 2 . ^^^ We found that both the SH 2 domain and phosphotyrosine binding ( PTB ) domain of Shc are important for BCR induced tyrosine phosphorylation of Shc and the subsequent binding of Grb 2 to Shc . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| The adaptor protein BLNK / SLP 65 plays a pivotal role in BCR signal transduction by coupling Syk activation to downstream elements such as Grb 2 , phospholipase C gamma , Vav and Nck . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
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 . ^^^ The Grb 2 binding site is required for the induction of chronic myeloid leukemia like disease in mice by the Bcr / Abl tyrosine kinase . ^^^ A tyrosine to phenylalanine mutation ( Y177F ) at this site blocks the co association of Bcr / Abl and Grb 2 in vivo and impairs focus formation by Bcr / Abl in fibroblasts . ^^^ However , the Bcr / Abl Y177F mutant can transform hematopoietic cell lines and primary bone marrow cells in vitro , so the importance of the Bcr / Abl Grb 2 interaction to myeloid and lymphoid leukemogenesis in vivo is unclear . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| Moreover , we demonstrate that addition of both linker for activation of T cells ( LAT ) and Grb 2 related adaptor downstream of Shc ( Gads ) to SLP 76 allow SLP 76 to be recruited into GEMs , whereby the BCR function is reconstituted . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| Gab 1 expression also increased BCR induced tyrosine phosphorylation of SHP 2 as well as the binding of Grb 2 to SHP 2 . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| The method has been used to measure mercury concentrations in six coal reference materials , SRM 1632b ( 77 . 4 ng / g ) , SRM 1632c ( 94 . 3 ng / g ) , BCR 40 ( 433 . 2 ng / g ) , BCR 180 ( 125 . 0 ng / g ) , BCR 181 ( 135 . 8 ng / g ) , and SARM 20 ( 252 . 6 ng / g ) , as well as a coal fly ash , SRM 1633b ( 143 . 1 ng / g ) . ^^^ |
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| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| Total uncertainty budget calculation for the determination of mercury in incineration ash ( BCR 176R ) by atomic fluorescence spectrometry . ^^^ The mercury mass fraction has been determined by atomic fluorescence spectrometry ( AFS ) in the framework of the project `` Certification of a reference material ( trace elements in fly ash ) in replacement of BCR CRM 176 ' ' . ^^^ |
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| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NTAL becomes rapidly tyrosine phosphorylated upon cross linking of the B cell receptor ( BCR ) or of high affinity Fcgamma and Fc epsilon receptors of myeloid cells and then associates with the cytoplasmic signaling molecules Grb 2 , Sos 1 , Gab 1 , and c Cbl . ^^^ |
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| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| This review briefly summarises the current understanding and therapy of CML and then discusses in more detail basic laboratory research that attempts to target Grb 2 , an adaptor protein known to directly interact with the Bcr portion of the Bcr Abl fusion protein . ^^^ |
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| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| We demonstrate here that adaptor molecules Grb 2 and BLNK , in addition to Vav , are required for efficient Rac 1 activation in response to BCR stimulation . ^^^ |
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| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| Bcr FGFR 1 binds Grb 2 via Bcr Tyr 177 and induces CML like leukemia in mice , whereas Bcr FGFR1 / Y177F lacks Grb 2 binding and causes EMS like disease . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| Upon BCR activation , LAB is phosphorylated and interacts with Grb 2 . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| This procedure was used for determination of antimony in natural water , soil , vegetation , and a certified sample of a city waste incineration ash ( BCR 176 ) . . ^^^ |
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| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| To gain further insight into the importance of Grb 2 for CML , peptides that disrupt Grb 2 SoS complexes were tested . ^^^ Furthermore , cell fractions that are enriched for blast cells from CML patients with active disease were also incubated with the Grb 2 blocker peptides . ^^^ These results show that , in addition to the direct targeting of Bcr Abl , selective inhibition of Grb 2 protein complexes may be a therapeutic option for a significant number of CML patients . . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ 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 . ^^^ |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P11274 and P62993 |
Pubmed |
SVM Score :0.0 |
| NA |
|