Sakurai H, Miyoshi H, Mizukami J, Sugita T
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., 16-89 Kashima 3-chome, Yodogawa-ku, 532-8505, Osaka, Japan.
FEBS Lett. 2000 Jun 2;474(2-3):141-5. doi: 10.1016/s0014-5793(00)01588-x.
TAK1 is a mitogen-activated protein kinase kinase kinase (MAP3K) that is involved in the c-Jun N-terminal kinase/p38 MAPKs and NF-kappaB signaling pathways. Here, we characterized the molecular mechanisms of TAK1 activation by its specific activator TAB1. Autophosphorylation of two threonine residues in the activation loop of TAK1 was necessary for TAK1 activation. Association with TAK1 and induction of TAK1 autophosphorylation required the C-terminal 24 amino acids of TAB1, but full TAK1 activation required additional C-terminal Ser/Thr rich sequences. These results demonstrated that the association between the kinase domain of TAK1 and the C-terminal TAB1 triggered the phosphorylation-dependent TAK1 activation mechanism.
TAK1是一种丝裂原活化蛋白激酶激酶激酶（MAP3K），参与c-Jun氨基末端激酶/p38 MAPK和核因子κB信号通路。在此，我们阐述了TAK1被其特异性激活剂TAB1激活的分子机制。TAK1激活环中两个苏氨酸残基的自磷酸化是TAK1激活所必需的。与TAK1结合并诱导TAK1自磷酸化需要TAB1的C末端24个氨基酸，但TAK1的完全激活需要额外的C末端富含丝氨酸/苏氨酸的序列。这些结果表明，TAK1的激酶结构域与TAB1的C末端之间的结合触发了磷酸化依赖性TAK1激活机制。
