In human, phosphorylation of MKK4 (MAP2K4) and MKK7 (MAP2K7) by TAK1 occurs at the typical Ser-Xaa-Ala-Xaa-Thr motif in their activation loops.
Residues involved in activation of these protein kinases correspond to human Ser271, Thr275 in MKK7 and Ser257, Thr261 in MKK4.
Cell lines lacking MKK4 exhibit defective activation of JNK and AP-1 dependent transcription activity in response to some cellular stresses; JNK and p38 MAPK activities were decreased by around 80% and 20%, respectively, following deletion of the mkk4 gene.
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
Nishida, E, Shibuya, H, Shirakabe, K, Ueno, N, Oishi, I, Matsumoto, K, Yamaguchi, K, Irie, K, Taniguchi, T
Kawai, T, Takeuchi, O, Sanjo, H, Takeda, K, Ninomiya-Tsuji, J, Sato, S, Yamamoto, M, Akira, S, Matsumoto, K
protein serine/threonine kinase activity of Activated TAK complexes [cytosol]
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