The protein product of the c-cbl protooncogene is the 120-kDa tyrosine-phosphorylated protein in Jurkat cells activated via the T cell antigen receptor.
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Donovan JA, Wange RL, Langdon WY, Samelson LE
The protein product of the c-cbl protooncogene is the 120-kDa tyrosine-phosphorylated protein in Jurkat cells activated via the T cell antigen receptor.
J Biol Chem. 1994 Sep 16;269(37):22921-4.
- PubMed ID
- 8083187 [ View in PubMed]
- Abstract
Tyrosine phosphorylation of multiple cellular proteins is a critical event in T cell receptor (TCR)-mediated activation. This pathway has also been implicated in cellular transformation in multiple systems. The viral oncogene v-cbl is the transforming gene of a murine retrovirus that induces pre-B cell lymphomas and myelogenous leukemias. The product of its cellular homolog, p120cbl, is a 120-kDa cytoplasmic protein that is non-transforming when overexpressed. Here we show that the 120-kDa protein tyrosine phosphorylated in Jurkat T cells upon TCR engagement is p120cbl. Following stimulation through the TCR, this tyrosine phosphorylation is rapid and reversible. Tyrosine-phosphorylated p120cbl binds to glutathione S-transferase fusion proteins generated from SH2 domains of the Fyn, Lck, and Blk protein tyrosine kinases, GTPase-activating protein and phospholipase C gamma. The p120cbl from unactivated and activated cells also binds to full-length glutathione S-transferase-Grb2 and the Grb2 N-terminal SH3 domain, but not to the Grb2 C-terminal SH3 domain. Additionally, p120cbl binds to SH3 domains of Fyn and Lck, but not Blk. These data expand our knowledge of protein tyrosine kinase signaling pathways in T cells by identifying a prominent tyrosine kinase substrate. This protein, the product of the cellular homolog of a transforming oncogene, can interact with several known signaling molecules.