Kinase Subfamily TAK1
Kinase Classification: Group TKL: Family MLK: Subfamily TAK1
Evolution
TAK1 is found in all studied holozoa. It has a single copy in human (TAK1/MAP3K7), with two members in nematodes, three in Drosophila and expanded to 8 in sponge. A muscle-specific splicing isoform is conserved throughout deuterostomes [1], and modulated by TGFb.
Domain Structure
TAK1 proteins have an N-terminal kinase domain and a partially-conserved C-terminus.
Functions
TAK1 (TGF beta Activated Kinase 1) transduces signals from TGF beta receptors, TNF receptors and IL-1R to NFkB, and can also act as a MAP3K to activate JNK MAPK signaling, in both Drosophila and mammals. TAK1 forms complexes with TRAF6 and the pseudophosphatase TAB1. In Drosophilids, where TAB1 is lost, there are some scattered changes in conserved TAK1 residues. TAB2 is another TAK1-interacting protein which functions both in Drosophila and mammals, and modulates both Jnk and NFkB signaling [2], and has two human homologs, TAB2 and TAB3.
A good summary of TAK1 functions across species is found at The Interactive Fly.
References
- Venables JP, Vignal E, Baghdiguian S, Fort P, and Tazi J. Tissue-specific alternative splicing of Tak1 is conserved in deuterostomes. Mol Biol Evol. 2012 Jan;29(1):261-9. DOI:10.1093/molbev/msr193 |
- Zhuang ZH, Sun L, Kong L, Hu JH, Yu MC, Reinach P, Zang JW, and Ge BX. Drosophila TAB2 is required for the immune activation of JNK and NF-kappaB. Cell Signal. 2006 Jul;18(7):964-70. DOI:10.1016/j.cellsig.2005.08.020 |
