CD95 (APO-1/Fas) induces activation of SAP kinases downstream of ICE-like proteases

Michael A. Cahill, Marcus E. Peter, Frank C. Kischkel, Arul M. Chinnaiyan, Vishva M. Dixit, Peter H. Krammer, Alfred Nordheim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

124 Scopus citations

Abstract

Triggering of CD95 (APO-1/Fas) on different T- and B-cell lines resulted in the induction of a number of kinases (35 kDa, 38 kDa, 46 kDa and 54 kDa) that phosphorylate c-Jun and to a lesser extent Histone H1. Activation of these kinases was independent of protein biosynthesis and preceded apoptotic DNA degradation. The kinase activation pattern was specific for CD95 triggering since a variety of physical or chemical inducers of T- and B-cell apoptosis activated different kinases. The kinase activities at 46 and 54 kDa contained members of the stress-activated family of protein kinases (JNK/SAPK). Activation of the CD95-specific set of kinases was prevented by treating cells with the ICE-inhibiting peptide N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk) or by overexpression of the cow pox virus serpin CrmA. However, despite inhibition of ICE-like proteases the death signal was readily initiated at the cell membrane since a CD95 death-inducing signaling complex (DISC) was formed. Thus, our results demonstrate that ICE-like proteases in the CD95 pathway function downstream of the DISC but upstream of SAP kinases.

Original languageEnglish (US)
Pages (from-to)2087-2096
Number of pages10
JournalOncogene
Volume13
Issue number10
StatePublished - Dec 19 1996

Keywords

  • Apoptosis
  • CD95 (APO-1/FAS)
  • DISC
  • MAP kinase
  • Signal transduction

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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