Crk interacts with tyrosine-phosphorylated p116 upon T cell activation.
Products of the crk oncogene are expressed in all tissues. Crk proteins are composed exclusively of Src homology 2 (SH2) and Src homology 3 (SH3) domains, and they have been implicated in intracellular signaling. For example, they participate as mediators of Ras activation during nerve growth factor stimulation of PC12 pheochromocytoma cells. We examined the role of Crk proteins during T cell receptor-mediated signaling and observed that Crk proteins specifically interact, via their SH2 domains, with a tyrosine-phosphorylated 116-kDa protein upon T cell activation. p116 may be related to the recently cloned fibroblast p130cas and/or p120-Cbl. In addition, we observed that GST-Crk fusion proteins and Crk-L bind, most likely via their SH3 domain, to C3G, a Ras guanine nucleotide exchange factor. Thus, the interaction of Crk with p116 and C3G strongly implicates Crk as a mediator of T cell receptor signaling, possibly involved in Ras activation.
Sawasdikosol
S
S
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Ravichandran
K S
KS
Lee
K K
KK
Chang
J H
JH
Burakoff
S J
SJ
D000310:Adrenal Gland Neoplasms; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D006825:Hybridomas; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D050736:Oncogene Protein v-crk; D016716:PC12 Cells; D010673:Pheochromocytoma; D010750:Phosphoproteins / Q000378:metabolism; D019000:Phosphotyrosine; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D015703:Antigens, CD; D015704:CD4 Antigens; D016827:CD8 Antigens; D050736:Oncogene Protein v-crk; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D015682:Retroviridae Proteins, Oncogenic; D019000:Phosphotyrosine; D014443:Tyrosine