Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1

TAK1 is a mitogen-activated protein kinase kinase kinase (MAP3K) that is in volved in the c-Jun N-terminal kinase/p38 MAPKs and NF-kappa B signaling pa thways. Here, we characterized the molecular mechanisms of TAK1 activation by its specific activator TAB1. Autophosphorylation of two threonine residu es in the activation loop of TAK1 was necessary for TAK1 activation. Associ ation with TAK1 and induction of TAK1 autophosphorylation required the C-te rminal 24 amino acids of TAB1, but full TAK1 activation required additional C-terminal Ser/Thr rich sequences, These results demonstrated that the ass ociation between the kinase domain of TAK1 and the C-terminal TAB1 triggere d the phosphorylation-dependent TAK1 activation mechanism. (C) 2000 Federat ion of European Biochemical Societies.