TYROSINE PHOSPHORYLATION-DEPENDENT SUPPRESSION OF A VOLTAGE-GATED K-LYMPHOCYTES UPON FAS STIMULATION( CHANNEL IN T)

Selective cell death plays a critical role in the development of the i mmune system and in the elimination of target cells expressing foreign antigens. Most of programmed cell death occurs by apoptosis, Apoptoti c cell death of lymphocytes can be triggered by ligation of APO-1/Fas (CD95) antigen (Suda, T., and Nagata, S. (1994) J. Exp. Med. 179, 873- 879; Nagata, S., and Golstein, P. (1995) Science 267, 1449-1456). We f ind that activation of Fas leads to the inhibition of the voltage-depe ndent n-type K+ channels (Kv1.3) studied by patch clamp technique in J urkat T lymphocytes, Tyrosine kinases have been shown to be crucial in Fas-induced cell death (Eischen, C. M., Dick, C. J,, and Leibson, P. J. (1994) J. Immunol. 153, 1947-1954), The inhibition of the current i s correlated with the tyrosine phosphorylation of immunoprecipitated a nd blotted K+ channel protein. We show, that the Src-like protein-tyro sine kinase inhibitor herbimycin A and the deficiency of the p56(lck) tyrosine kinase in mutant Jurkat cells abolished the channel inhibitio n and phosphorylation by anti-Fas antibody, while reconstitution of th e p56(lck) kinase partly restored these effects of Fas receptor trigge ring. These results suggest a regulation of n-type K+ channels by tyro sine kinases upon Fas receptor triggering, which might be important fo r apoptosis.