Phospho-TAB2 (Ser372) (D5A4) Rabbit mAb #8155

TAK1 is a mitogen-activated protein kinase kinase kinase activated by TGF-β and various pro-inflammatory signals (1,2). In vivo, TAK1 activation requires its association with TAK1 binding protein 1 (TAB1), which triggers TAK1 autophosphorylation at Thr184 and Thr187 (3,4). The TAB2 adaptor protein links TAK1 with TRAF6 to mediate TAK1 activation following IL-1 stimulation (5). Once activated, TAK1 phosphorylates the MAPK kinases MKK4 and MKK3/6, which activate JNK and p38 MAPK, respectively. TAK1 and TRAF6 also activate the NF-κB pathway by phosphorylating the NF-κB inducing kinase (NIK) to trigger subsequent activation of IKK (2,6). In addition to TAK1, TAB1 interacts with and activates p38α MAPK (7). Targeted disruption of the TAB1 gene in mice causes a drastic reduction in TAK1 activity and leads to embryonic lethality (8).
TAK1 is associated with TAB1 as well as either TAB2 or TAB3 (9). Activation of TAK1 is triggered by K63-ubiquitination of TRAF6, resulting in binding to TAB2 and TAB3 and autophosphorylation of TAK1 (10-12). Multiple phosphorylation sites have been identified in all three TAB family members that are triggered by IL-1 (13,14). TAB2 phosphorylation was identified at Ser372 and Ser524 (14).