U. Senftleben et al., Activation by IKK alpha of a second, evolutionary conserved, NF-kappa B signaling pathway, SCIENCE, 293(5534), 2001, pp. 1495-1499
In mammals, the canonical nuclear factor kappaB (NF-kappaB) signaling pathw
ay activated in response to infections is based on degradation Of I kappaB
inhibitors. This pathway depends on the I kappaB kinase (IKK), which contai
ns two catalytic subunits, IKK alpha and IKK beta. IKK beta is essential fo
r inducible I kappaB phosphorylation and degradation, whereas IKK alpha is
not. Here we show that IKK alpha is required for B cell maturation, formati
on of secondary lymphoid organs, increased expression of certain NF-kappaB
target genes, and processing of the NF-kappa B2 (p100) precursor. IKK alpha
preferentially phosphorylates NF-kappa B2, and this activity requires its
phosphorylation by upstream kinases, one of which may be NF-kappaB-inducing
kinase (NIK). IKK alpha is therefore a pivotal component of a second NF-ka
ppaB activation pathway based on regulated NF-kappa B2 processing rather th
an I kappaB degradation.