Selective association of the p59fyn 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 contrast, the p56lck, another important T-cell tyrosine kinase, is directly linked to CD4 or CD8 surface glycoproteins with high stoichiometry. To document the mode of p59fyn interaction with proteins of the plasma membrane, proteins co-precipitating with the kinase in extracts of purified membranes were phosphorylated in vitro, resolved by two-dimensional electrophoresis and compared with those co-precipitating with the p56lck kinase. The p59fyn, but not the p56lck kinase, associates with three phosphotyrosyl-proteins among which a 95- to 100-kDa component also binds to the src-homology 2 (SH2) domain of the v-crk oncoprotein. This p95-100 phosphoprotein is not the p95Var product of the Vav proto-oncogene; it is recovered much more effectively from 32Pi-metabolically 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 into the plasma membrane by specific phosphotyrosylproteins and so differ from the p56lck tyrosine kinase, which binds preferentially to the CD4 and CD8 transmembrane adhesion glycoproteins.
Arni
S
S
Department of Pathology, Faculty of Medicine, Centre Médical Universitaire, Geneva, Switzerland.
Senaldi
G
G
Poincelet
M
M
Hoessli
D C
DC
D000818:Animals; D018797:Cell Cycle Proteins; D015180:Electrophoresis, Gel, Two-Dimensional; D016399:Lymphoma, T-Cell / Q000378:metabolism*; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D050736:Oncogene Protein v-crk; D010750:Phosphoproteins / Q000378:metabolism*; D019000:Phosphotyrosine; D011233:Precipitin Tests; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D051567:Proto-Oncogene Proteins c-vav; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D018797:Cell Cycle Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D050736:Oncogene Protein v-crk; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D015682:Retroviridae Proteins, Oncogenic; C496619:Vav1 protein, mouse; D019000:Phosphotyrosine; D014443:Tyrosine; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn