NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser-176.

Article Details

Citation

Ling L, Cao Z, Goeddel DV

NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser-176.

Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3792-7.

PubMed ID
9520446 [ View in PubMed
]
Abstract

Activation of the transcription factor NF-kappaB by inflammatory cytokines involves the successive action of NF-kappaB-inducing kinase (NIK) and two IkappaB kinases, IKK-alpha and IKK-beta. Here we show that NIK preferentially phosphorylates IKK-alpha over IKK-beta, leading to the activation of IKK-alpha kinase activity. This phosphorylation of IKK-alpha occurs specifically on Ser-176 in the activation loop between kinase subdomains VII and VIII. A mutant form of IKK-alpha containing alanine at residue 176 cannot be phosphorylated or activated by NIK and acts as a dominant negative inhibitor of interleukin 1- and tumor necrosis factor-induced NF-kappaB activation. Conversely, a mutant form of IKK-alpha containing glutamic acid at residue 176 is constitutively active. Thus, the phosphorylation of IKK-alpha on Ser-176 by NIK may be required for cytokine-mediated NF-kappaB activation.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Inhibitor of nuclear factor kappa-B kinase subunit alphaO15111Details