Activation by IKKα of a second, evolutionary conserved, NF-κB signaling pathway

U. Senftleben, Y. Cao, G. Xiao, F. R. Greten, G. Krähn, G. Bonizzi, Y. Chen, Y. Hu, A. Fong, S. C. Sun, M. Karin

Research output: Contribution to journalArticlepeer-review

Abstract

In mammals, the canonical nuclear factor κB (NF-κB) signaling pathway activated in response to infections is based on degradation of IκB inhibitors. This pathway depends on the IκB kinase (IKK), which contains two catalytic subunits, IKKα and IKKβ. IKKβ is essential for inducible IκB phosphorylation and degradation, whereas IKKα is not. Here we show that IKKα is required for B cell maturation, formation of secondary lymphoid organs, increased expression of certain NF-κB target genes, and processing of the NF-κB2 (p100) precursor. IKKα preferentially phosphorylates NF-κB2, and this activity requires its phosphorylation by upstream kinases, one of which may be NF-κB-inducing kinase (NIK). IKKα is therefore a pivotal component of a second NF-κB activation pathway based on regulated NF-κB2 processing rather than IκB degradation.

Original languageEnglish
Pages (from-to)1495-1499
Number of pages5
JournalScience
Volume293
Issue number5534
DOIs
Publication statusPublished - Aug 24 2001

ASJC Scopus subject areas

  • General

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