The proto-oncogene Vav product is constitutively tyrosine-phosphorylated in normal human immature T cells

The proto-oncogene Vav product is markedly tyrosine-phosphorylated after the recruitment of various receptors of cells of hematopoietic origin, including mature T cells. Recent studies on Vav-deficient mice have clearly implicated the product of the proto-oncogene Vav in intrathymic T cell development. Vav tyrosine phosphorylation is probably crucial to connect early tyrosine kinase(s) to downstream molecular events leading to cell division and maturation that occur in the thymus. We investigated the tyrosine phosphorylation of Vav in human thymocytes. Immunoblotting experiments demonstrate that, as in mature T cells, tyrosine phosphorylation of Vav is induced following thymocyte stimulation through the T cell receptor. The main observation, however, is that an important fraction of cellular Vav is constitutively tyrosine-phosphorylated in freshly isolated cells. This phenomenon takes place apparently both in the CD4+CD8+ and the more mature CD4+CD8- and CD4-CD8+ thymocyte cell subsets. Co-immunoprecipitation experiments showed, moreover, that a small amount of Vav is engaged in the multimolecular complex that includes elements of the T cell receptor and the T cell specific ZAP-70 tyrosine kinase. Altogether, these data suggest that a critical pathway for T cell development in the human thymus likely involves the permanent activation of Vav in vivo.