Ceramide-induced inhibition of T lymphocyte voltage-gated potassium channel is mediated by tyrosine kinases

DOI Web Site 2 Citations
  • Erich Gulbins
    Department of Physiology, University of Tübingen, Gmelinstrasse 5, 72076 Tübingen, Germany
  • Ildiko Szabo
    Department of Physiology, University of Tübingen, Gmelinstrasse 5, 72076 Tübingen, Germany
  • Katharina Baltzer
    Department of Physiology, University of Tübingen, Gmelinstrasse 5, 72076 Tübingen, Germany
  • Florian Lang
    Department of Physiology, University of Tübingen, Gmelinstrasse 5, 72076 Tübingen, Germany

Abstract

<jats:p>The n-type K<jats:sup>+</jats:sup>channel (n-K<jats:sup>+</jats:sup>, K<jats:sub>v</jats:sub>1.3) 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<jats:sup>+</jats:sup>channel activity and induces a tyrosine phosphorylation of the K<jats:sub>v</jats:sub>1.3 protein in Jurkat T lymphocytes. Tyrosine phosphorylation of the n-K<jats:sup>+</jats:sup>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<jats:sup>+</jats:sup>channel inhibition and tyrosine phosphorylation, we propose a ceramide-initiated activation of p56lck resulting in tyrosine phosphorylation and inhibition of the n-K<jats:sup>+</jats:sup>channel protein.</jats:p>

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