Tab1

TAB1 is an activator subunit of TAK1 (transforming growth factor β activated kinase 1). When ectopically expressed together with TAK1, TAB1 can augment the kinase activity of TAK1. The C-terminal 68-amino acid region of TAB1 is sufficient for binding to and the activation of TAK1. A conserved sequence motif, PYVDXA/TXF, is found in the C-terminal regions of mammalian TAB1, Xenopus TAB1, and the C. elegans TAB1 homolog TAP-1, and is essential for TAK1 binding. The N-terminal region of TAB1 interacts with X-chromosome-linked inhibitor of apoptosis protein (XIAP). XIAP also associates with the bone morphogenetic protein (BMP) receptor. XIAP links the TAB1-TAK1 complex with the BMP receptor. C. elegans TAP-1 regulates Wnt signaling by polarizing responding cells during embryogenesis. Although TAB1 enhances TAK1 activity, when overexpressed together with TAK1, the endogenous interaction of TAB1 with TAK1 can be detected in the absence of extracellular stimuli. TAK1 activity is also regulated by other signaling molecules including TAK1 binding protein 2 (TAB2) and a TAB2 related protein, TAK1-binding protein 3 (TAB3). TAB1 is not structurally related to TAB2 or TAB3. TAB1 was also isolated as a p38α binding protein. TAB1 binds to p38α but not p38β2, p38γ or p38δ. TAB1 shares sequence homology with protein phosphatase 2c, yet there is no evidence for TAB1-linked phosphatase activity.