Tyrosine phosphorylation-dependent suppression of a voltage-gated K+ channel in T lymphocytes upon Fas stimulation.
Selective cell death plays a critical role in the development of the immune system and in the elimination of target cells expressing foreign antigens. Most of programmed cell death occurs by apoptosis. Apoptotic 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 find that activation of Fas leads to the inhibition of the voltage-dependent n-type K+ channels (Kv1.3) studied by patch clamp technique in Jurkat 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 is correlated with the tyrosine phosphorylation of immunoprecipitated and blotted K+ channel protein. We show, that the Src-like protein-tyrosine kinase inhibitor herbimycin A and the deficiency of the p56(lck) tyrosine kinase in mutant Jurkat cells abolished the channel inhibition and phosphorylation by anti-Fas antibody, while reconstitution of the p56(lck) kinase partly restored these effects of Fas receptor triggering. These results suggest a regulation of n-type K+ channels by tyrosine kinases upon Fas receptor triggering, which might be important for apoptosis.
Szabò
I
I
Physiology Institute I, Eberhard-Karls University, D-72076 Tübingen, Germany.
Gulbins
E
E
Apfel
H
H
Zhang
X
X
Barth
P
P
Busch
A E
AE
Schlottmann
K
K
Pongs
O
O
Lang
F
F
D017209:Apoptosis; D016227:Benzoquinones; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015640:Ion Channel Gating; D047029:Lactams, Macrocyclic; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008564:Membrane Potentials; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D015221:Potassium Channels; D011809:Quinones; D019014:fas Receptor; D017828:Rifabutin; D019000:Phosphotyrosine; C020754:herbimycin; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases