TAK1 is a mitogen-activated protein kinase kinase kinase that can be activated by TGF-?, bone morphogenetic protein and other cytokines including IL-1. In vivo activation of TAK1 requires association with TAK1 binding protein 1 (TAB1), which triggers phosphorylation of TAK1. Another adaptor protein, TAB2, links TAK1 with TRAF6 and mediates TAK1 activation upon IL-1 stimulation. Once activated, TAK1 phosphorylates MAPK kinases MKK4 and MKK3/6, which activate p38 MAPK and JNK, respectively. In addition, TAK1 activates the NF-?B pathway by interacting with TRAF6 and phosphorylating the NF-?B inducing kinase (NIK).