Involvement of ASK1 in Ca2+ - Induced p38 MAP kinase activation

Kohsuke Takeda, Atsushi Matsuzawa, Hideki Nishitoh, Kei Tobiume, Satoshi Kishida, Jun Ninomiya-Tsuji, Kunihiro Matsumoto, Hidenori Ichijo

Research output: Contribution to journalArticlepeer-review

143 Citations (Scopus)

Abstract

The mammalian mitogen-activated protein (MAP) kinase kinase kinase apoptosis signal-regulating kinase 1 (ASK1) is a pivotal component in cytokine- and stress-induced apoptosis. It also regulates cell differentiation and survival through p38 MAP kinase activation. Here we show that Ca2+ signalling regulates the ASK1-p38 MAP kinase cascade. Ca2+ influx evoked by membrane depolarization in primary neurons and synaptosomes induced activation of p38, which was impaired in those derived from ASK1-deficient mice. Ca2+/calmodulin-dependent protein kinase type II (CaMKII) activated ASK1 by phosphorylation. Moreover, p38 activation induced by the expression of constitutively active CaMKII required endogenous ASK1. Thus, ASK1 is a critical intermediate of Ca2+ signalling between CaMKII and p38 MAP kinase.

Original languageEnglish
Pages (from-to)161-166
Number of pages6
JournalEMBO Reports
Volume5
Issue number2
DOIs
Publication statusPublished - 2004 Feb
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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