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The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase mediates the signaling transduction induced by TGF beta and morphogenetic protein (BMP), and controls a variety of cell functions including transcription regulation and apoptosis. TAK1 is a central regulator of cell death and is activated through a diverse set of intra- and extracellular stimuli. TAK1 regulates cell survival not solely through NF-κB but also through NF-κB-independent pathways such as oxidative stress and receptor-interacting protein kinase 1 (RIPK1) kinase activity-dependent pathway.[2] In response to IL-1, this protein forms a kinase complex including TRAF6, MAP3K7P1/TAB1 and MAP3K7P2/TAB2; this complex is required for the activation of nuclear factor kappa B. This kinase can also activate MAPK8/JNK, MAP2K4/MKK4, and thus plays a role in the cell response to environmental stresses. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.[3]
↑ 4.04.1Mochida Y, Takeda K, Saitoh M, Nishitoh H, Amagasa T, Ninomiya-Tsuji J, Matsumoto K, Ichijo H (October 2000). "ASK1 inhibits interleukin-1-induced NF-kappa B activity through disruption of TRAF6-TAK1 interaction". J. Biol. Chem. 275 (42): 32747–52. doi:10.1074/jbc.M003042200. PMID10921914.
↑ 5.05.15.25.3Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K (March 1999). "The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway". Nature. 398 (6724): 252–6. doi:10.1038/18465. PMID10094049.
↑Sakurai H, Miyoshi H, Toriumi W, Sugita T (April 1999). "Functional interactions of transforming growth factor beta-activated kinase 1 with IkappaB kinases to stimulate NF-kappaB activation". J. Biol. Chem. 274 (15): 10641–8. doi:10.1074/jbc.274.15.10641. PMID10187861.
↑ 7.07.1Sakurai H, Miyoshi H, Mizukami J, Sugita T (June 2000). "Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1". FEBS Lett. 474 (2–3): 141–5. doi:10.1016/s0014-5793(00)01588-x. PMID10838074.
↑Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ (July 2001). "TAK1 is a ubiquitin-dependent kinase of MKK and IKK". Nature. 412 (6844): 346–51. doi:10.1038/35085597. PMID11460167.
↑Channavajhala PL, Wu L, Cuozzo JW, Hall JP, Liu W, Lin LL, Zhang Y (November 2003). "Identification of a novel human kinase supporter of Ras (hKSR-2) that functions as a negative regulator of Cot (Tpl2) signaling". J. Biol. Chem. 278 (47): 47089–97. doi:10.1074/jbc.M306002200. PMID12975377.
↑ 12.012.1Takaesu G, Kishida S, Hiyama A, Yamaguchi K, Shibuya H, Irie K, Ninomiya-Tsuji J, Matsumoto K (April 2000). "TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway". Mol. Cell. 5 (4): 649–58. doi:10.1016/s1097-2765(00)80244-0. PMID10882101.
↑Kimura N, Matsuo R, Shibuya H, Nakashima K, Taga T (June 2000). "BMP2-induced apoptosis is mediated by activation of the TAK1-p38 kinase pathway that is negatively regulated by Smad6". J. Biol. Chem. 275 (23): 17647–52. doi:10.1074/jbc.M908622199. PMID10748100.
↑Yanagisawa M, Nakashima K, Takeda K, Ochiai W, Takizawa T, Ueno M, Takizawa M, Shibuya H, Taga T (December 2001). "Inhibition of BMP2-induced, TAK1 kinase-mediated neurite outgrowth by Smad6 and Smad7". Genes Cells. 6 (12): 1091–9. doi:10.1046/j.1365-2443.2001.00483.x. PMID11737269.
↑Hanada M, Ninomiya-Tsuji J, Komaki K, Ohnishi M, Katsura K, Kanamaru R, Matsumoto K, Tamura S (February 2001). "Regulation of the TAK1 signaling pathway by protein phosphatase 2C". J. Biol. Chem. 276 (8): 5753–9. doi:10.1074/jbc.M007773200. PMID11104763.
↑Sorrentino A, Thakur N, Grimsby S, Marcusson A, von Bulow V, Schuster N, Zhang S, Heldin CH, Landström M (October 2008). "The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner". Nat. Cell Biol. 10 (10): 1199–207. doi:10.1038/ncb1780. PMID18758450.
Hirose T, Fujimoto W, Tamaai T, Kim KH, Matsuura H, Jetten AM (1995). "TAK1: molecular cloning and characterization of a new member of the nuclear receptor superfamily". Mol. Endocrinol. 8 (12): 1667–80. doi:10.1210/me.8.12.1667. PMID7708055.
Yamaguchi K, Shirakabe K, Shibuya H, Irie K, Oishi I, Ueno N, Taniguchi T, Nishida E, Matsumoto K (1996). "Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction". Science. 270 (5244): 2008–11. doi:10.1126/science.270.5244.2008. PMID8533096.
Shibuya H, Yamaguchi K, Shirakabe K, Tonegawa A, Gotoh Y, Ueno N, Irie K, Nishida E, Matsumoto K (1996). "TAB1: an activator of the TAK1 MAPKKK in TGF-beta signal transduction". Science. 272 (5265): 1179–82. doi:10.1126/science.272.5265.1179. PMID8638164.
Wang W, Zhou G, Hu MC, Yao Z, Tan TH (1997). "Activation of the hematopoietic progenitor kinase-1 (HPK1)-dependent, stress-activated c-Jun N-terminal kinase (JNK) pathway by transforming growth factor beta (TGF-beta)-activated kinase (TAK1), a kinase mediator of TGF beta signal transduction". J. Biol. Chem. 272 (36): 22771–5. doi:10.1074/jbc.272.36.22771. PMID9278437.
Sakurai H, Shigemori N, Hasegawa K, Sugita T (1998). "TGF-beta-activated kinase 1 stimulates NF-kappa B activation by an NF-kappa B-inducing kinase-independent mechanism". Biochem. Biophys. Res. Commun. 243 (2): 545–9. doi:10.1006/bbrc.1998.8124. PMID9480845.
Yan ZH, Karam WG, Staudinger JL, Medvedev A, Ghanayem BI, Jetten AM (1998). "Regulation of peroxisome proliferator-activated receptor alpha-induced transactivation by the nuclear orphan receptor TAK1/TR4". J. Biol. Chem. 273 (18): 10948–57. doi:10.1074/jbc.273.18.10948. PMID9556573.
Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K (1999). "The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway". Nature. 398 (6724): 252–6. doi:10.1038/18465. PMID10094049.
Sakurai H, Miyoshi H, Toriumi W, Sugita T (1999). "Functional interactions of transforming growth factor beta-activated kinase 1 with IkappaB kinases to stimulate NF-kappaB activation". J. Biol. Chem. 274 (15): 10641–8. doi:10.1074/jbc.274.15.10641. PMID10187861.
Delhase M, Hayakawa M, Chen Y, Karin M (1999). "Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation". Science. 284 (5412): 309–13. doi:10.1126/science.284.5412.309. PMID10195894.
Zhou G, Lee SC, Yao Z, Tan TH (1999). "Hematopoietic progenitor kinase 1 is a component of transforming growth factor beta-induced c-Jun N-terminal kinase signaling cascade". J. Biol. Chem. 274 (19): 13133–8. doi:10.1074/jbc.274.19.13133. PMID10224067.
Kimura N, Matsuo R, Shibuya H, Nakashima K, Taga T (2000). "BMP2-induced apoptosis is mediated by activation of the TAK1-p38 kinase pathway that is negatively regulated by Smad6". J. Biol. Chem. 275 (23): 17647–52. doi:10.1074/jbc.M908622199. PMID10748100.
Hofer-Warbinek R, Schmid JA, Stehlik C, Binder BR, Lipp J, de Martin R (2000). "Activation of NF-kappa B by XIAP, the X chromosome-linked inhibitor of apoptosis, in endothelial cells involves TAK1". J. Biol. Chem. 275 (29): 22064–8. doi:10.1074/jbc.M910346199. PMID10807933.
Sakurai H, Miyoshi H, Mizukami J, Sugita T (2000). "Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1". FEBS Lett. 474 (2–3): 141–5. doi:10.1016/S0014-5793(00)01588-X. PMID10838074.