TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway

The TAK1 MAPKKK mediates activation of JNK and NF-kappa B in the IL-1-activ ated signaling pathway. Here we report the identification of TAB2, a novel intermediate in the IL-1 pathway that functionally links TAK1 to TRAF6. Exp ression of TAB2 induces JNK and NF-kappa B activation, whereas a dominant-n egative mutant TAB2 impairs their activation by IL-1. IL-1 stimulates trans location of TAB2 from the membrane to the cytosol where it mediates the IL- 1-dependent association of TAK1 with TRAF6. These results define TAB:! as a n adaptor linking TAK1 and TRAF6 and as a mediator of TAK1 activation in th e ii-i signaling pathway.