SELECTIVE ASSOCIATION OF THE P59(FYN) TYROSINE KINASE WITH MURINE T-LYMPHOMA MEMBRANE PHOSPHOPROTEINS

The p59fyn oncogene product, a tyrosine kinase of the src family, is a key enzyme in T-lymphocyte transmembrane signalling that is not known to bind with high stoichiometry to any surface receptor protein. By c ontrast, the p56lck, another important T-cell tyrosine kinase, is dire ctly linked to CD4 or CD8 surface glycoproteins with high stoichiometr y. To document the mode of p59fyn interaction with proteins of the pla sma membrane, proteins co-precipitating with the kinase in extracts of purified membranes were phosphorylated in vitro. resolved by two-dime nsional electrophoresis and compared with those co-precipitating with the p56lck kinase. The p59fyn, but not the p56lck kinase, associates w ith three phosphotvrosyl-proteins among which a 95- to 100-kDa compone nt also binds to the src-homology 2 (SH2) domain of the v-crk oncoprot ein. This p95-100 phosphoprotein is not the p95Vav product of the Vav proto-oncogene; it is recovered much more effectively from P-32i-metab olically labelled cells after treatment with the tyrosine phosphatase inhibitor phenylarsenoxide, suggesting that its phosphorylation state is controlled by tyrosine phosphatases. The p59fyn may be integrated i nto the plasma membrane by specific phosphotyrosylproteins and so diff er from the p56lck tyrosine kinase, which binds preferentially to the CD4 and CD8 transmembrane adhesion glycoproteins.