activated human TAK1 phosphorylates MKK3/MKK6

Stable Identifier
Reaction [transition]
Homo sapiens
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Human MKK3 (MAP2K4) and MKK6 (MAP2K6) are two closely related dual-specificity protein kinases. Both are activated by cellular stress and inflammatory cytokines, and both phosphorylate and activate p38 MAP kinase at its activation site Thr-Gly-Tyr but do not phosphorylate or activate Erk1/2 or SAPK/JNK.

Activation of MKK3 and MKK6 occurs through phosphorylation of serine and threonine residues at the typical Ser-Xaa-Ala-Xaa-Thr motif in their activation loop. Residues involved into these protein kinases activation correspond to human sites Ser189 and Thr193 for MKK3 and Ser207 and Thr211 for MKK6 .

Literature References
PubMed ID Title Journal Year
8622669 MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway

Davis, RJ, Whitmarsh, AJ, Derijard, B, Raingeaud, J, Barrett, T

Mol Cell Biol 1996
15837794 Simultaneous blockade of NFkappaB, JNK, and p38 MAPK by a kinase-inactive mutant of the protein kinase TAK1 sensitizes cells to apoptosis and affects a distinct spectrum of tumor necrosis factor [corrected] target genes

Kracht, M, Wolter, S, Resch, K, Dittrich-Breiholz, O, Wirth, D, Thiefes, A, Mushinski, JF, Luckow, B, Schneider, H, Graue, N, Dörrie, A, Hoffmann, E

J Biol Chem 2005
8533096 Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction

Nishida, E, Shibuya, H, Shirakabe, K, Ueno, N, Oishi, I, Matsumoto, K, Yamaguchi, K, Irie, K, Taniguchi, T

Science 1995
16186825 Essential function for the kinase TAK1 in innate and adaptive immune responses

Kawai, T, Takeuchi, O, Sanjo, H, Takeda, K, Ninomiya-Tsuji, J, Sato, S, Yamamoto, M, Akira, S, Matsumoto, K

Nat Immunol 2005
Catalyst Activity

protein serine/threonine kinase activity of Activated TAK complexes [cytosol]

Orthologous Events
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