TAK1 (also known as MAP3K7), a part of the serine/threonine kinase family, is a versatile protein with many signaling functions. Originally identified as a TGF- beta-activated kinase, TAK1 interacts with TGF- beta-receptor and TRAF6 to modulate TGF- beta activation of JNK and p38. It has additional roles in activation of p38 and JNK through Wnt, BMP, and activin signaling pathways as well in response to thyroid hormone, osmotic stress, endothelin, and ephrine. Through activation of von Hippel-Lindau tumor suppressor expression, TAK1 represses PDGF-B, integrin beta1 and integrin beta5, promoting proper wound healing. TAK1 also plays an essential role in IKK activation in numerous signaling pathways including IL-1, IL-6, IL-18, TNF, CD40, TLR, and RIG-I. Activation of the TAK1-IKK pathway requires TAB2/3 and ubiquitination. In this process, TAB2/3 binds to the C-terminal region of TAK1 and becomes polyubiquitinated, TAK1 is autophosphorylated at Thr178, Thr184, Thr187 and Ser192, and finally TAK1 phosphorylates IKK- beta. Additionally, TAK1 represses human telomerase reverse transcriptase suggesting a role in regulation of cell lifespan.
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Protein Aliases: M3K7; mitogen activated protein kinase kinase kinase 7; Mitogen-activated protein kinase kinase kinase 7; RP1-154G14.1; TGF-beta activated kinase 1; TGF-beta-activated kinase 1; transforming growth factor beta-activated kinase 1; Transforming growth factor-beta-activated kinase 1
Gene Aliases: B430101B05; C87327; MAP3K7; MEKK7; TAK1; TGF1a