Crk Interacts with Tyrosine-phosphorylated p116 upon T Cell Activation

Sawasdikosol, Sansana; Ravichandran, Kodi S.; Lee, Kyungah Kay; Chang, Jinhong; Burakoff, Steven J.

doi:10.1074/jbc.270.7.2893

Cited by 76 publications

(55 citation statements)

References 31 publications

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“…Known targets include those speci®cally interacting with the N-terminal SH3 domain and those binding to the SH2 domain. CRKL has been shown to associate in vivo with the guanine nucleotide releasing factors SOS, (ten Hoeve et al, 1994a), an activator of ras (Egan et al, 1993;RozakisAdcock et al, 1993), and C3G Sawasdikosol et al, 1995) through its SH3 domain. C3G is an activator of GTPase Rap1, which is a suppressor of ras transformation (Gotoh et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…C3G was originally identi®ed as a CRKbinding protein and contains several binding sites for the Crk N-SH3 domain (Tanaka et al, 1994;Knudsen et al, 1994). Despite the high a nity of Crk for C3G in vitro , CRK is not complexed in vivo with C3G in T-cells, whereas CRKL is (Sawasdikosol et al, 1995;Reedquist et al, 1996). This provides a ®rst example of di erent biological roles for these related adaptor molecules.…”

Section: Discussionmentioning

confidence: 99%

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Tyrosine 207 in CRKL is the BCR/ABL phosphorylation site

et al. 1997

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BCR/ABL has a causal role in Philadelphia (Ph)-chromosome positive leukemia. The SH2/SH3 adapter protein CRKL is a major substrate of the deregulated BCR/ABL tyrosine kinase and is aberrantly tyrosinephosphorylated in Ph-positive leukemia cells. In this study, experiments were pursued to identify and analyse the CRKL phosphorylation site(s). In an in vitro kinase assay, CRKL phosphorylation by the abl kinase was limited to a small region between the two CRKL SH3 domains. Within this region, mutation of tyrosine residue 207 yielded a mutant CRKL which could not be phosphorylated by BCR/ABL. Stable overexpression of CRKL or CRKL-Y207F did not transform NIH3T3 cells, while the Y207F mutation eliminated tyrosinephosphorylation of CRKL. These studies indicate that Y207 in CRKL represents the major in vivo phosphorylation site. Phosphorylation of Y207 provides a binding site for the CRKL SH2 domain and potentially for other SH2-containing proteins. The Y207F mutation in CRKL did not enhance or decrease association with various target signalling proteins, including SOS or C3G, which interact speci®cally with the CRKL N-SH3 domain. These ®ndings suggest that complex formation with cellular targets is not modulated by CRKL tyrosinephosphorylation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tyrosine 207 in CRKL is the BCR/ABL phosphorylation site

et al. 1997

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“…The pp70 corresponded to paxillin [39] as detected with an anti-paxillin antibody (Transduction Laboratories) (results not shown). The phosphoprotein pp130 probably represents a Cas-related protein [40] because antibodies directed against Cas (Transduction Laboratories and Upstate Biotechnology), Cbl (Santa Cruz Biotechnology) and FAK (Transduction Laboratories) did not recognize this protein.…”

Section: Crk Sh2 Domain Interacts With the Igf-i Receptor From Whole mentioning

confidence: 99%

Interaction in vitro of the product of the c-Crk-II proto-oncogene with the insulin-like growth factor I receptor

Koval

Blakesley

Roberts

et al. 1998

Biochemical Journal

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The Crk proto-oncogene product is an SH2 and SH3 domaincontaining adaptor protein. We have previously demonstrated that Crk-II becomes rapidly tyrosine-phosphorylated in response to stimulation with insulin-like growth factor I (IGF-I) and might be involved in the IGF-I receptor signalling pathway. To determine whether this involvement includes the direct interaction of Crk-II with the cytoplasmic region of the receptor, studies were performed in itro with glutathione S-transferase (GST) fusion proteins containing various domains of Crk-II. The kinase assay in itro showed that activated IGF-I receptors efficiently phosphorylated the GST-Crk-II fusion protein. This phosphorylation was dependent on the presence of the SH2 domain and Tyr-221 located in the spacer region between the two SH3 domains. Mutation of Tyr-221 not only prevented phosphorylation of GST-Crk in itro, but also significantly increased the ability of GST-Crk proteins to co-precipitate activated IGF-I receptors from total cell lysates. Additional binding experiments in itro showed that Crk-II might interact with the phosphorylated IGF-I receptor through its SH2 domain. To elucidate which

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“…The c-Cbl proto-oncogene was originally identi®ed as a cellular homologue of v-Cbl oncogene, which was cloned from the Cas NS-1 murine leukemia virus (Langdon et al, 1989). Upon phosphorylation, c-Cbl can bind to the SH2 domains of the p85 subunit of PI3 kinase and CRK (Sawasdikosol et al, 1995;Panchamoorthy et al, 1996;Reedquist et al, 1996). Therefore c-Cbl can act as an adaptor protein which connects LTK with the PI3 kinase pathway.…”

Section: The Survival Signal Of Ltk Is Sensitive To Wortmanninmentioning

confidence: 99%

The phosphatidylinositol 3′ kinase pathway is required for the survival signal of leukocyte tyrosine kinase

et al. 1997

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Leukocyte tyrosine kinase (LTK) is a receptor tyrosine kinase which belongs to the insulin receptor superfamily and is mainly expressed in pre-B lymphocytes and neuronal tissues. Recently, we demonstrated that LTK utilizes Shc and IRS-1 as two major substrates and while both equally activate the Ras pathway, only IRS-1 suppresses apoptosis of hematopoietic cells, suggesting the existence of another unidenti®ed signaling pathway downstream of IRS-1, which is relevant to the antiapoptotic activity. In the present study, we found that wortmannin, a speci®c inhibitor of phosphatidylinositol 3' (PI3)-kinase, abolished the survival e ects of LTK. Although c-Cbl is found to be phosphorylated by LTK and therefore is a second candidate linking LTK with the PI3-kinase pathway along with IRS-1, we found that the p85 subunit of PI3 kinase directly binds to tyrosine 753 of LTK, which is located within a YXXM motif, a consensus binding amino acid sequence for the SH2 domain of p85, but fails to bind to IRS-1 or c-Cbl. Ba/ F3 cells which stably express the EGF receptor-LTK chimeric receptor carrying a mutation at tyrosine 753 fell into apoptotic death even in the presence of EGF, indicating that the PI3 kinase pathway is required for the survival e ects of LTK.

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Crk Interacts with Tyrosine-phosphorylated p116 upon T Cell Activation

Cited by 76 publications

References 31 publications

Tyrosine 207 in CRKL is the BCR/ABL phosphorylation site

Tyrosine 207 in CRKL is the BCR/ABL phosphorylation site

Interaction in vitro of the product of the c-Crk-II proto-oncogene with the insulin-like growth factor I receptor

The phosphatidylinositol 3′ kinase pathway is required for the survival signal of leukocyte tyrosine kinase

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