IkappaB kinase alpha (IKKalpha) regulation of IKKbeta kinase activity.

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Yamamoto Y, Yin MJ, Gaynor RB

IkappaB kinase alpha (IKKalpha) regulation of IKKbeta kinase activity.

Mol Cell Biol. 2000 May;20(10):3655-66.

PubMed ID

10779355 [ View in PubMed

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Abstract

Two related kinases, IkappaB kinase alpha (IKKalpha) and IKKbeta, phosphorylate the IkappaB proteins, leading to their degradation and the subsequent activation of gene expression by NF-kappaB. IKKbeta has a much higher level of kinase activity for the IkappaB proteins than does IKKalpha and is more critical than IKKalpha in modulating tumor necrosis factor alpha activation of the NF-kappaB pathway. These results indicate an important role for IKKbeta in activating the NF-kappaB pathway but leave open the question of the role of IKKalpha in regulating this pathway. In the current study, we demonstrate that IKKalpha directly phosphorylates IKKbeta. Moreover, IKKalpha either directly or indirectly enhances IKKbeta kinase activity for IkappaBalpha. Finally, transfection studies to analyze NF-kappaB-directed gene expression suggest that IKKalpha is upstream of IKKbeta in activating the NF-kappaB pathway. These results indicate that IKKalpha, in addition to its previously described ability to phosphorylate IkappaBalpha, can increase the ability of IKKbeta to phosphorylate IkappaBalpha.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Acetylsalicylic acid	Inhibitor of nuclear factor kappa-B kinase subunit beta	Protein	Humans	Unknown	Not Available	Details