Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway: A new mode of regulation of the MAP kinase cascade

Hiroshi Matsuura, Hideki Nishitoh, Kohsuke Takeda, Atsushi Matsuzawa, Teruo Amagasa, Michihiko Ito, Katsuji Yoshioka, Hidenori Ichijo

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)

Abstract

JSAP1 (also termed JIP3) is a scaffold protein that interacts with specific components of the JNK signaling pathway. Apoptosis signal-regulating kinase (ASK) 1 is a MAP kinase kinase kinase that activates the JNK and p38 mitogen-activated protein (MAP) kinase cascades in response to environmental stresses such as reactive oxygen species. Here we show that JSAP1 bound ASK1 and enhanced ASK1- and H 2O 2-induced JNK activity. ASK1 phosphorylated JSAP1 in vitro and in vivo, and the phosphorylation facilitated interactions of JSAP1 with SEK1/MKK4, MKK7 and JNK3. Furthermore, ASK1-dependent phosphorylation was required for JSAP1 to recruit and thereby activate JNK in response to H 2O 2. We thus conclude that JSAP1 functions not only as a simple scaffold, but it dynamically participates in signal transduction by forming a phosphorylation-dependent signaling complex in the ASK1-JNK signaling module.

Original languageEnglish
Pages (from-to)40703-40709
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number43
DOIs
Publication statusPublished - 2002 Oct 25

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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