Ceramide-induced inhibition of T lymphocyte voltage-gated potassium channel is mediated by tyrosine kinases.
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 p56lck upon cellular treatment with the ceramide analog C6-ceramide. Because genetic deficiency of p56lck 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 p56lck resulting in tyrosine phosphorylation and inhibition of the n-K+ channel protein.
Gulbins
E
E
Department of Physiology, University of Tübingen, Gmelinstrasse 5, 72076 Tübingen, Germany.
Szabo
I
I
Baltzer
K
K
Lang
F
F
D002518:Ceramides / Q000494:pharmacology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D019169:Jurkat Cells; D015221:Potassium Channels / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000378:metabolism*
D002518:Ceramides; D015221:Potassium Channels; D011505:Protein-Tyrosine Kinases