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Pervanadate simulates the effects of interleukin-2 (IL-2) in human T cells and provides evidence for the activation of two distinct tyrosine kinase pathways by IL-2.

1994; Elsevier BV; Volume: 269; Issue: 38 Linguagem: Inglês

10.1016/s0021-9258(17)31530-2

1083-351X

Gerald A. Evans, Gonzalo G. Garcia, Rebecca A. Erwin, O. M. Zack Howard, William L. Farrar,

Neutrophil, Myeloperoxidase and Oxidative Mechanisms

Pervanadate has been shown to rapidly increase the level of tyrosine phosphorylation in intact cells. Because one of the most rapidly detectable events following treatment of human T cells with interleukin-2 (IL-2) is tyrosine kinase activation, we were interested to determine whether pervanadate could act to induce IL-2-associated events. We show here that pervanadate does act to induce IL-2 signal transduction pathways as determined by induction of mitogenesis and interferon gamma production in normal human T cells and the factor independent T cell line YT. Analysis of signal transduction events shows that pervanadate induces the activity of the src family of tyrosine kinases lck and fyn and the tyrosine phosphorylation of a major IL-2 responsive protein of 97 kDa. Pervanadate does not, however, induce the activity of tyrosine kinases associated with the IL-2 receptor or the phosphorylation of a major IL-2 responsive protein of 116 kDa (Jak-3). Together these data suggest that src family kinase activation is a down stream event following IL-2 stimulation and is not directly associated with the activation of the IL-2 receptor-associated tyrosine kinase. The data also imply that tyrosine phosphorylation of p116/Jak-3 is strictly associated with activation of tyrosine kinases associated with the IL-2 receptor. With the use of pervanadate as a tool, we have established a dissociation of src family kinases with IL-2 receptor activation and imply the involvement of two distinct tyrosine kinase pathways, a receptor-associated pathway closely coupled with Jak-3 phosphorylation and a downstream pathway involving src family kinase activation.