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Biochem Biophys Res Commun. 1998 Feb 13;243(2):545-9.

TGF-beta-activated kinase 1 stimulates NF-kappa B activation by an NF-kappa B-inducing kinase-independent mechanism.

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Lead Generation Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan.


Several mitogen-activated protein kinase kinase kinases (MAPKKKs), including NF-kappa B-inducing kinase (NIK), play critical roles in NF-kappa B activation. We isolated cDNA for human TGF-beta activated kinase 1 (TAK1), a member of the MAPKKK family, and evaluated its ability to stimulate NF-kappa B activation. Overexpression of TAK1 together with its activator protein, TAK1 binding protein 1 (TAB1), induced the nuclear translocation of NF-kappa B p50/p65 heterodimer accompanied by the degradation of I kappa B alpha and I kappa B beta, and the expression of kappa B-dependent reporter gene. A dominant negative mutant of NIK did not inhibit TAK1-induced NF-kappa B activation. These results suggest that TAK1 induces NF-kappa B activation through a novel NIK-independent signaling pathway.

[Indexed for MEDLINE]

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