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 the deletion of the mkk4 gene.
Chicken MKK4 protein as confirmed by mRNA sequence shows 96% identity to human MKK4 (UniProtKB sequence data using NCBI BLASTP 2.2.20). Multiple sequence alignment of the proteins by ClustalW demonstrated that chicken MKK4 serine residue 224 and threonine 228 correspond to human Ser257 and Thr261, that are required for the activation.
Since no MKK7 ortholog was identified in the chicken genome, only chicken MKK4 protein is annotated in the chicken JNK pathway as a homolog of the well characterized human MKK4 / MKK7 proteins.
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 chicken TAK1 complexes [cytosol]
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