Binding of JNK/SAPK to MEKK1 is regulated by phosphorylation

Ewen D. Gallagher, Shuichan Xu, Carolyn Moomaw, Clive A. Slaughter, Melanie H. Cobb

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

We sought to characterize the role of upstream kinases in the regulation of the MAP3 kinase MEKK1 and the potential impact on signaling to MAP kinase cascades. We find that the MAP4 kinase PAK1 phosphorylates the amino terminus of MEKK1 on serine 67. We show that serine 67 lies in a D domain, which binds to the c-Jun-NH2-terminal kinase/stress-activated protein kinases (JNK/SAPK). Serine 67 is constitutively phosphorylated in resting 293 cells, but is dephosphorylated following exposure to stress stimuli such as anisomycin and UV irradiation. Phosphorylation of this site inhibits binding of JNK/SAPK to MEKK1. Thus, we propose a mechanism by which the MEKK1-dependent JNK/SAPK pathway is negatively regulated by PAK through phosphorylation of serine 67.

Original languageEnglish (US)
Pages (from-to)45785-45792
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number48
DOIs
StatePublished - Nov 29 2002

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this