Activation by IKKα of a Second, Evolutionary Conserved, NF-κB Signaling Pathway

Uwe Senftleben; Yixue Cao; Gutian Xiao; Florian R. Greten; Gertraud Krähn; Giuseppina Bonizzi; Yi Chen; Yinling Hu; Abraham Fong; Shao‐Cong Sun; Michael Karin

doi:10.1126/science.1062677

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.

Keywords

IκB kinaseKinasePhosphorylationSignal transductionCell biologyNF-κBNFKB1BiologyGeneCancer researchTranscription factorGenetics

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Publication Info

Year: 2001
Type: article
Volume: 293
Issue: 5534
Pages: 1495-1499
Citations: 1342
Access: Closed

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APA Style

                            
                                
                                    Uwe Senftleben, 
                                
                                    Yixue Cao, 
                                
                                    Gutian Xiao
                                
                                et al.
                            
                            (2001). 
                            Activation by IKKα of a Second, Evolutionary Conserved, NF-κB Signaling Pathway. 
                            Science
                            , 293
                            (5534)
                            , 1495-1499.
                            https://doi.org/10.1126/science.1062677
                        

Identifiers

DOI: 10.1126/science.1062677