Activation of the IκBα kinase complex by MEKK1, a kinase of the JNK pathway

Frank S. Lee, Jeremiah Hagler, Zhijian J. Chen, Tom Maniatis

Research output: Contribution to journalArticle

643 Scopus citations

Abstract

Both NF-κB and c-Jun are activated by cytokines such as TNF-α and by stresses such as UV irradiation. A key step in the activation of NF-κB is the phosphorylation of its inhibitor, IκBα, by a ubiquitination-inducible multiprotein kinase complex (IκBα kinase). A central kinase in the c-Jun activation pathway is mitogen-activated protein kinase/ERK kinase kinase-1 (MEKK1). Here, we show that MEKK1 induces the site-specific phosphorylation of IκBα in vivo and, most strikingly, can directly activate the IκBα kinase complex in vitro. Thus, MEKK1 is a critical component of both the c- Jun and NF-κB stress response pathways. Since the IκBα kinase complex can be independently activated by ubiquitination or MEKK1-dependent phosphorylation, it may be an integrator of multiple signal transduction pathways leading to the activation of NF-κB.

Original languageEnglish (US)
Pages (from-to)213-222
Number of pages10
JournalCell
Volume88
Issue number2
DOIs
StatePublished - Jan 24 1997

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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