Referenced in: none

Automatically associated channels: SK1

Title: Involvement of ASK1 in Ca2+-induced p38 MAP kinase activation.

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

Journal, date & volume: EMBO Rep., 2004 Feb , 5, 161-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/14749717

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.