TAK1-TAB1 fusion protein: a novel constitutively active mitogen-activated protein kinase kinase kinase that stimulates AP-1 and NF-kappa B signaling pathways

Sakurai H; Nishi A; Sato N; Mizukami J; Miyoshi H; Sugita T

Biochemical and Biophysical Research Communications, Vol.297, No.5, 1277-1281, 2002

DOI10.1016/S0006-291X(02)02379-3 Export Citation

TAK1-TAB1 fusion protein: a novel constitutively active mitogen-activated protein kinase kinase kinase that stimulates AP-1 and NF-kappa B signaling pathways

Sakurai H, Nishi A, Sato N, Mizukami J, Miyoshi H, Sugita T

TAK1 mitogen-activated protein kinase kinase kinase (MAP3K) is activated by its specific activator, TAK1-binding protein 1 (TAB 1). A constitutively active TAK1 mutant has not yet been generated due to the indispensable requirement of TAB1 for TAK1 kinase activity. In this study, we generated a novel constitutively active TAK1 by fusing its kinase domain to the minimal TAK1-activation domain of TAB1. Co-immunoprecipitation assay demonstrated that these domains interacted intra-molecularly. The TAK1-TAB1 fusion protein showed a significant MAP3K activity in vitro and activated c-Jun N-terminal kinase/p38 MAPKs and IkappaB kinase in vivo, which was followed by increased production of interleukin-6. These results indicate that the fusion protein is useful for characterizing the physiological roles of the TAK1-TAB1 complex. (C) 2002 Elsevier Science (USA). All rights reserved.