Phosphorylation of Thr-516 and Ser-520 in the kinase activation loop of MEKK3 is required for lysophosphatidic acid-mediated optimal IκB kinase β (IKKβ)/nuclear factor-κB (NF-κB) activation

Wenjing Sun, Ningling Ge, Yang Yu, Susan Burlingame, Xiaonan Li, Ming Zhang, Shenglong Ye, Songbin Fu, Jianhua Yang*

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

MEKK3 serves as a critical intermediate signaling molecule in lysophosphatidic acid-mediated nuclear factor-κB (NF-κB) activation. However, the precise regulation for MEKK3 activation at the molecular level is still not fully understood. Here we report the identification of two regulatory phosphorylation sites at Thr-516 and Ser-520 within the kinase activation loop that is essential for MEKK3-mediated IκB kinase β (IKKβ)/NF-κB activation. Substitution of these two residues with alanine abolished the ability of MEKK3 to activate IKKβ/NF-κB, whereas replacement with acidic residues rendered MEKK3 constitutively active. Furthermore, substitution of these two residues with alanine abolished the ability of MEKK3 to mediate lysophosphatidic acid-induced optimal IKKβ/NF-κB activation.

Original languageEnglish (US)
Pages (from-to)7911-7918
Number of pages8
JournalJournal of Biological Chemistry
Volume285
Issue number11
DOIs
StatePublished - Mar 12 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Phosphorylation of Thr-516 and Ser-520 in the kinase activation loop of MEKK3 is required for lysophosphatidic acid-mediated optimal IκB kinase β (IKKβ)/nuclear factor-κB (NF-κB) activation'. Together they form a unique fingerprint.

  • Cite this