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Ceramide-Induced Inhibition of T Lymphocyte Voltage-Gated Potassium Channel is Mediated by Tyrosine Kinases
Erich Gulbins, Ildiko Szabo, Katharina Baltzer and Florian Lang
Proceedings of the National Academy of Sciences of the United States of America
Vol. 94, No. 14 (Jul. 8, 1997), pp. 7661-7666
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/42736
Page Count: 6
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The n-type K+ channel (n-K+, Kv1.3) in lymphocytes has been recently implicated in the regulation of Fas-induced programmed cell death. Here, we demonstrate that ceramide, a lipid metabolite synthesized upon Fas receptor ligation, inhibits n-K+ channel activity and induces a tyrosine phosphorylation of the Kv1.3 protein in Jurkat T lymphocytes. Tyrosine phosphorylation of the n-K+ channel correlated with an activation of the Src-like tyrosine kinase p561ck upon cellular treatment with the ceramide analog C6-ceramide. Because genetic deficiency of p561ck or inhibition of Src-like tyrosine kinases by herbimycin A prevented ceramide-mediated n-K+ channel inhibition and tyrosine phosphorylation, we propose a ceramide-initiated activation of p561ck resulting in tyrosine phosphorylation and inhibition of the n-K+ channel protein.
Proceedings of the National Academy of Sciences of the United States of America © 1997 National Academy of Sciences