TY - JOUR
T1 - Activation by IKKα of a second, evolutionary conserved, NF-κB signaling pathway
AU - Senftleben, U.
AU - Cao, Y.
AU - Xiao, G.
AU - Greten, F. R.
AU - Krähn, G.
AU - Bonizzi, G.
AU - Chen, Y.
AU - Hu, Y.
AU - Fong, A.
AU - Sun, S. C.
AU - Karin, M.
PY - 2001/8/24
Y1 - 2001/8/24
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1062677
DO - 10.1126/science.1062677
M3 - Article
C2 - 11520989
AN - SCOPUS:17944378526
SN - 0036-8075
VL - 293
SP - 1495
EP - 1499
JO - Science
JF - Science
IS - 5534
ER -