Tak1

Summary

Gene Symbol: Tak1
Description: mitogen-activated protein kinase kinase kinase 7
Alias: CSCF, FMD2, MEKK7, TAK1, TGF1a, mitogen-activated protein kinase kinase kinase 7, TGF-beta activated kinase 1, transforming growth factor-beta-activated kinase 1
Species: human
Products:     Tak1

Top Publications

  1. Safina A, Ren M, Vandette E, Bakin A. TAK1 is required for TGF-beta 1-mediated regulation of matrix metalloproteinase-9 and metastasis. Oncogene. 2008;27:1198-207 pubmed
    ..Here, we present evidence that TGF-beta-activated protein kinase 1 (TAK1) is critical for TGF-beta regulation of MMP-9 and the metastatic potential of breast cancer cell line MDA-MB-231...
  2. Takaesu G, Surabhi R, Park K, Ninomiya Tsuji J, Matsumoto K, Gaynor R. TAK1 is critical for IkappaB kinase-mediated activation of the NF-kappaB pathway. J Mol Biol. 2003;326:105-15 pubmed
    ..we utilized small interfering RNAs (siRNAs) directed against IKKalpha, IKKbeta and the upstream regulatory kinase TAK1 in order to better define their roles in cytokine-induced activation of the NF-kappaB pathway...
  3. Hamidi A, von Bulow V, Hamidi R, Winssinger N, Barluenga S, Heldin C, et al. Polyubiquitination of transforming growth factor ? (TGF?)-associated kinase 1 mediates nuclear factor-?B activation in response to different inflammatory stimuli. J Biol Chem. 2012;287:123-33 pubmed publisher
    ..The TGF?-associated kinase 1 (TAK1) is an upstream regulator of NF-?B signaling...
  4. Sakurai H, Miyoshi H, Toriumi W, Sugita T. Functional interactions of transforming growth factor beta-activated kinase 1 with IkappaB kinases to stimulate NF-kappaB activation. J Biol Chem. 1999;274:10641-8 pubmed
    ..We recently reported that the overexpression of transforming growth factor-beta-activated kinase 1 (TAK1), a member of the mitogen-activated protein kinase kinase kinase family, together with its activator TAK1-binding ..
  5. Wang C, Deng L, Hong M, Akkaraju G, Inoue J, Chen Z. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature. 2001;412:346-51 pubmed
    ..Here we report the purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism...
  6. Pertel T, Hausmann S, Morger D, Züger S, Guerra J, Lascano J, et al. TRIM5 is an innate immune sensor for the retrovirus capsid lattice. Nature. 2011;472:361-5 pubmed publisher
    ..known as UBE2N-UBE2V1), TRIM5 catalyses the synthesis of unattached K63-linked ubiquitin chains that activate the TAK1 (also known as MAP3K7) kinase complex and stimulate AP-1 and NF?B signalling...
  7. Lam C, Tan M, Tan S, Tang M, Cheung P, Tan N. TAK1 regulates SCF expression to modulate PKB? activity that protects keratinocytes from ROS-induced apoptosis. Cell Death Differ. 2011;18:1120-9 pubmed publisher
    ..Herein, we show that transforming growth factor ?-activated kinase 1 (TAK1) directly regulates stem cell factor (SCF) expression, which activates the protein kinase B (PKB)? pro-survival ..
  8. Oeckinghaus A, Wegener E, Welteke V, Ferch U, Arslan S, Ruland J, et al. Malt1 ubiquitination triggers NF-kappaB signaling upon T-cell activation. EMBO J. 2007;26:4634-45 pubmed
    ..Thus, our data demonstrate that induced Malt1 ubiquitination is critical for the engagement of CBM and IKK complexes, thereby directing TCR signals to the canonical NF-kappaB pathway. ..
  9. Kajino T, Omori E, Ishii S, Matsumoto K, Ninomiya Tsuji J. TAK1 MAPK kinase kinase mediates transforming growth factor-beta signaling by targeting SnoN oncoprotein for degradation. J Biol Chem. 2007;282:9475-81 pubmed
    ..Here, we report the role of TAK1 as a SnoN protein kinase...

More Information

Publications77

  1. Broglie P, Matsumoto K, Akira S, Brautigan D, Ninomiya Tsuji J. Transforming growth factor beta-activated kinase 1 (TAK1) kinase adaptor, TAK1-binding protein 2, plays dual roles in TAK1 signaling by recruiting both an activator and an inhibitor of TAK1 kinase in tumor necrosis factor signaling pathway. J Biol Chem. 2010;285:2333-9 pubmed publisher
    Transforming growth factor beta-activated kinase 1 (TAK1) kinase is an indispensable signaling intermediate in tumor necrosis factor (TNF), interleukin 1, and Toll-like receptor signaling pathways...
  2. Xiao H, Qian W, Staschke K, Qian Y, Cui G, Deng L, et al. Pellino 3b negatively regulates interleukin-1-induced TAK1-dependent NF kappaB activation. J Biol Chem. 2008;283:14654-64 pubmed publisher
    ..Pellino 3b on IL-1-induced IRAK degradation correlated with the inhibitory effect of Pellino 3b on the IL-1-induced TAK1-dependent pathway, suggesting that a positive role of IRAK degradation in IL-1 induced TAK1 activation...
  3. Shambharkar P, Blonska M, Pappu B, Li H, You Y, Sakurai H, et al. Phosphorylation and ubiquitination of the IkappaB kinase complex by two distinct signaling pathways. EMBO J. 2007;26:1794-805 pubmed
    ..Further, we provide evidence that TAK1 is activated and recruited to the synapses in a CARMA1-independent manner and mediate IKKalpha/beta phosphorylation...
  4. Ono K, Ohtomo T, Ninomiya Tsuji J, Tsuchiya M. A dominant negative TAK1 inhibits cellular fibrotic responses induced by TGF-beta. Biochem Biophys Res Commun. 2003;307:332-7 pubmed
    Transforming growth factor-beta (TGF-beta) is crucially virulent in the progression of fibrotic disorders. TAK1 (TGF-beta activated kinase 1) is one of the mitogen-activated kinase kinase kinase (MAPKKK) that is involved in TGF-beta ..
  5. Sakurai H, Nishi A, Sato N, Mizukami J, Miyoshi H, Sugita T. TAK1-TAB1 fusion protein: a novel constitutively active mitogen-activated protein kinase kinase kinase that stimulates AP-1 and NF-kappaB signaling pathways. Biochem Biophys Res Commun. 2002;297:1277-81 pubmed
    b>TAK1 mitogen-activated protein kinase kinase kinase (MAP3K) is activated by its specific activator, TAK1-binding protein 1 (TAB1)...
  6. Strippoli R, Benedicto I, Foronda M, Perez Lozano M, Sánchez Perales S, López Cabrera M, et al. p38 maintains E-cadherin expression by modulating TAK1-NF-kappa B during epithelial-to-mesenchymal transition. J Cell Sci. 2010;123:4321-31 pubmed publisher
    ..Moreover, p38 inhibition increased the phosphorylation of TGF-?-activated kinase 1 (TAK1), NF-?B and I?B?...
  7. Kim S, Kwak J, Wang L, Choi M. Protein phosphatase 2A is a negative regulator of transforming growth factor-beta1-induced TAK1 activation in mesangial cells. J Biol Chem. 2008;283:10753-63 pubmed publisher
    b>TAK1 (transforming growth factor (TGF)-beta-activated kinase 1) is a serine/threonine kinase that is rapidly activated by TGF-beta1 and plays a vital function in its signal transduction...
  8. Yu Y, Ge N, Xie M, Sun W, Burlingame S, Pass A, et al. Phosphorylation of Thr-178 and Thr-184 in the TAK1 T-loop is required for interleukin (IL)-1-mediated optimal NFkappaB and AP-1 activation as well as IL-6 gene expression. J Biol Chem. 2008;283:24497-505 pubmed publisher
    b>TAK1 (transforming growth factor-beta-activated kinase 1), a mitogen-activated protein kinase kinase kinase, is activated by various cytokines, including interleukin-1 (IL-1)...
  9. Wu L, Nakano H, Wu Z. The C-terminal activating region 2 of the Epstein-Barr virus-encoded latent membrane protein 1 activates NF-kappaB through TRAF6 and TAK1. J Biol Chem. 2006;281:2162-9 pubmed
    ..Furthermore, we showed that TAK1 is required for NF-kappaB activation by LMP1...
  10. Kim S, Shim J, Chun E, Lee K. Reciprocal inhibition between the transforming growth factor-?-activated kinase 1 (TAK1) and apoptosis signal-regulating kinase 1 (ASK1) mitogen-activated protein kinase kinase kinases and its suppression by TAK1-binding protein 2 (TAB2), an adapter . J Biol Chem. 2012;287:3381-91 pubmed publisher
    ..In this study we demonstrated that transforming growth factor-?-activated kinase 1 (TAK1)-TAK1-binding protein 1 (TAB1) complex negatively regulates ASK1-mediated signaling, and TAB2 reciprocally ..
  11. Tian Y, Zhang Y, Zhong B, Wang Y, Diao F, Wang R, et al. RBCK1 negatively regulates tumor necrosis factor- and interleukin-1-triggered NF-kappaB activation by targeting TAB2/3 for degradation. J Biol Chem. 2007;282:16776-82 pubmed
    ..Taken together, our findings suggest that RBCK1 is involved in negative regulation of inflammatory signaling triggered by TNF and IL-1 through targeting TAB2/3 for degradation. ..
  12. Ninomiya Tsuji J, Kajino T, Ono K, Ohtomo T, Matsumoto M, Shiina M, et al. A resorcylic acid lactone, 5Z-7-oxozeaenol, prevents inflammation by inhibiting the catalytic activity of TAK1 MAPK kinase kinase. J Biol Chem. 2003;278:18485-90 pubmed
    b>TAK1, a member of the mitogen-activated kinase kinase kinase (MAPKKK) family, participates in proinflammatory cellular signaling pathways by activating JNK/p38 MAPKs and NF-kappaB...
  13. Shi M, Deng W, Bi E, Mao K, Ji Y, Lin G, et al. TRIM30 alpha negatively regulates TLR-mediated NF-kappa B activation by targeting TAB2 and TAB3 for degradation. Nat Immunol. 2008;9:369-77 pubmed publisher
    ..tripartite-motif protein TRIM30alpha, a RING protein, was induced by TLR agonists and interacted with the TAB2-TAB3-TAK1 adaptor-kinase complex involved in the activation of transcription factor NF-kappaB...
  14. Blanco S, Santos C, Lazo P. Vaccinia-related kinase 2 modulates the stress response to hypoxia mediated by TAK1. Mol Cell Biol. 2007;27:7273-83 pubmed
    ..Hypoxia induces an increase in the activity of TAK1, an atypical mitogen-activated protein kinase kinase kinase (MAPKKK), which responds to oxidative stress by ..
  15. Walsh M, Kim G, Maurizio P, Molnar E, Choi Y. TRAF6 autoubiquitination-independent activation of the NFkappaB and MAPK pathways in response to IL-1 and RANKL. PLoS ONE. 2008;3:e4064 pubmed publisher
    ..K63-linked autoubiquitination of TRAF6 is essential for formation and activation of a complex involving the kinase TAK1 and its adapters, TAB1 and TAB2...
  16. Kajino T, Ren H, Iemura S, Natsume T, Stefansson B, Brautigan D, et al. Protein phosphatase 6 down-regulates TAK1 kinase activation in the IL-1 signaling pathway. J Biol Chem. 2006;281:39891-6 pubmed
    b>TAK1 (transforming growth factor beta-activated kinase 1) is a serine/threonine kinase that is a mitogen-activated protein kinase kinase kinase and an essential intracellular signaling component in inflammatory signaling pathways...
  17. Fan Y, Yu Y, Shi Y, Sun W, Xie M, Ge N, et al. Lysine 63-linked polyubiquitination of TAK1 at lysine 158 is required for tumor necrosis factor alpha- and interleukin-1beta-induced IKK/NF-kappaB and JNK/AP-1 activation. J Biol Chem. 2010;285:5347-60 pubmed publisher
    Transforming growth factor-beta-activated kinase 1 (TAK1) plays an essential role in the tumor necrosis factor alpha (TNFalpha)- and interleukin-1beta (IL-1beta)-induced IkappaB kinase (IKK)/nuclear factor-kappaB (NF-kappaB) and c-Jun N-..
  18. Jensen L, Whitehead A. Pellino2 activates the mitogen activated protein kinase pathway. FEBS Lett. 2003;545:199-202 pubmed
    ..TRAF6 (tumor necrosis factor receptor associated factor 6) and that both Pellino1 and Pellino2 also interact with TAK1 (transforming growth factor-beta activated kinase 1)...
  19. Sakurai H, Miyoshi H, Mizukami J, Sugita T. Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1. FEBS Lett. 2000;474:141-5 pubmed
    b>TAK1 is a mitogen-activated protein kinase kinase kinase (MAP3K) that is involved in the c-Jun N-terminal kinase/p38 MAPKs and NF-kappaB signaling pathways...
  20. Delhase M, Hayakawa M, Chen Y, Karin M. Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation. Science. 1999;284:309-13 pubmed
    ..Once activated, IKKbeta autophosphorylated at a carboxyl-terminal serine cluster. Such phosphorylation decreased IKK activity and may prevent prolonged activation of the inflammatory response. ..
  21. Dai L, Aye Thu C, Liu X, Xi J, Cheung P. TAK1, more than just innate immunity. IUBMB Life. 2012;64:825-34 pubmed publisher
    Transforming growth factor ?-activated kinase 1 (TAK1) is a key regulator of the innate immunity and the proinflammatory signaling pathway...
  22. Tokarev A, Suarez M, Kwan W, Fitzpatrick K, Singh R, Guatelli J. Stimulation of NF-?B activity by the HIV restriction factor BST2. J Virol. 2013;87:2046-57 pubmed publisher
    ..induction of NF-?B by BST2 was impaired by inhibition of transforming growth factor ? (TGF-?)-activated kinase 1 (TAK1) or by calcium chelation, suggesting potential linkage to the mitogen-activated protein kinase and endoplasmic ..
  23. Shirakabe K, Yamaguchi K, Shibuya H, Irie K, Matsuda S, Moriguchi T, et al. TAK1 mediates the ceramide signaling to stress-activated protein kinase/c-Jun N-terminal kinase. J Biol Chem. 1997;272:8141-4 pubmed
    ..However, the molecular mechanism by which ceramide induces SAPK/JNK activation is unknown. Here we show that TAK1, a member of the mitogen-activated protein kinase kinase kinase family, is activated by treatment of cells with ..
  24. Emmerich C, Ordureau A, Strickson S, Arthur J, Pedrioli P, Komander D, et al. Activation of the canonical IKK complex by K63/M1-linked hybrid ubiquitin chains. Proc Natl Acad Sci U S A. 2013;110:15247-52 pubmed publisher
    ..The TGF-beta-activated kinase 1 (TAK1)-binding protein (TAB) 2 and TAB3 components of the TAK1 complex and the NFκB Essential Modifier (NEMO) ..
  25. Mao R, Fan Y, Mou Y, Zhang H, Fu S, Yang J. TAK1 lysine 158 is required for TGF-?-induced TRAF6-mediated Smad-independent IKK/NF-?B and JNK/AP-1 activation. Cell Signal. 2011;23:222-7 pubmed publisher
    Lys63-linked TAK1 polyubiquitination plays an essential role in the regulation of TAK1 activation. TRAF6-mediated Lys63-linked polyubiquitylation of TAK1 has been shown to be required for TGF-?-induced TAK1 activation...
  26. Shibuya H, Yamaguchi K, Shirakabe K, Tonegawa A, Gotoh Y, Ueno N, et al. TAB1: an activator of the TAK1 MAPKKK in TGF-beta signal transduction. Science. 1996;272:1179-82 pubmed
    ..A member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family, TAK1, was previously identified as a mediator in the signaling pathway of TGF-beta superfamily members...
  27. Melisi D, Xia Q, Paradiso G, Ling J, Moccia T, Carbone C, et al. Modulation of pancreatic cancer chemoresistance by inhibition of TAK1. J Natl Cancer Inst. 2011;103:1190-204 pubmed publisher
    TGF-?-activated kinase-1 (TAK1), a mitogen-activated protein kinase kinase kinase, functions in the activation of nuclear factor ?B (NF-?B) and activator protein-1, which can suppress proapoptotic signaling pathways and thus promote ..
  28. Postler T, Desrosiers R. The cytoplasmic domain of the HIV-1 glycoprotein gp41 induces NF-?B activation through TGF-?-activated kinase 1. Cell Host Microbe. 2012;11:181-93 pubmed publisher
    ..revealed that gp41CD-mediated activation occurs through the canonical NF-?B pathway via TGF-?-activated kinase 1 (TAK1)...
  29. Yao J, Kim T, Qin J, Jiang Z, Qian Y, Xiao H, et al. Interleukin-1 (IL-1)-induced TAK1-dependent Versus MEKK3-dependent NFkappaB activation pathways bifurcate at IL-1 receptor-associated kinase modification. J Biol Chem. 2007;282:6075-89 pubmed
    ..IRAK modification mutants, we uncovered two parallel IL-1-mediated signaling pathways for NFkappaB activation, TAK1-dependent and MEKK3-dependent, respectively. These two pathways bifurcate at the level of IRAK modification...
  30. Yamaguchi K, Shirakabe K, Shibuya H, Irie K, Oishi I, Ueno N, et al. Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction. Science. 1995;270:2008-11 pubmed
    ..A genetic selection based on a MAPK pathway in yeast was used to identify a mouse protein kinase (TAK1) distinct from other members of the MAPKKK family...
  31. Ninomiya Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K. The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature. 1999;398:252-6 pubmed
    ..However, the molecular mechanism by which NIK is activated is not understood. Here we show that the MAPKK kinase TAK1 acts upstream of NIK in the IL-1-activated signalling pathway and that TAK1 associates with TRAF6 during IL-1 ..
  32. Cheung P, Nebreda A, Cohen P. TAB3, a new binding partner of the protein kinase TAK1. Biochem J. 2004;378:27-34 pubmed
    We have identified a new binding partner of the TGFbeta (transforming growth factor-beta)-activated protein kinase (TAK1), termed TAB3 (TAK1-binding protein-3), which shares 48% amino acid sequence identity with TAB2...
  33. Li H, Kobayashi M, Blonska M, You Y, Lin X. Ubiquitination of RIP is required for tumor necrosis factor alpha-induced NF-kappaB activation. J Biol Chem. 2006;281:13636-43 pubmed
    ..Together, our studies provide the first genetic evidence that the ubiquitination of RIP is required for TNFalpha-induced NF-kappaB activation. ..
  34. Hacker H, Karin M. Regulation and function of IKK and IKK-related kinases. Sci STKE. 2006;2006:re13 pubmed
    ..Together, the IKKs and IKK-related kinases are instrumental for activation of the host defense system. This Review focuses on the functions of IKK and IKK-related kinases and the molecular mechanisms that regulate their activities. ..
  35. Kim S, Baik K, Baek K, Chah K, Kim K, Moon G, et al. S6K1 negatively regulates TAK1 activity in the toll-like receptor signaling pathway. Mol Cell Biol. 2014;34:510-21 pubmed publisher
    Transforming growth factor ? (TGF-?)-activated kinase 1 (TAK1) is a key regulator in the signals transduced by proinflammatory cytokines and Toll-like receptors (TLRs)...
  36. Lee H, Jang S, Kim H, Yoon J, Chung K. PINK1 stimulates interleukin-1?-mediated inflammatory signaling via the positive regulation of TRAF6 and TAK1. Cell Mol Life Sci. 2012;69:3301-15 pubmed publisher
    ..We show that PINK1 specifically binds to TRAF6 and TAK1, and facilitates the autodimerization and autoubiquitination of TRAF6...
  37. Yamazaki K, Gohda J, Kanayama A, Miyamoto Y, Sakurai H, Yamamoto M, et al. Two mechanistically and temporally distinct NF-kappaB activation pathways in IL-1 signaling. Sci Signal. 2009;2:ra66 pubmed publisher
    ..Although transforming growth factor-beta-activated kinase 1 (TAK1) and mitogen-activated protein kinase (MAPK) kinase kinase 3 (MEKK3) are both crucial for IL-1-dependent activation ..
  38. Kanayama A, Seth R, Sun L, Ea C, Hong M, Shaito A, et al. TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains. Mol Cell. 2004;15:535-48 pubmed
    The activation of NF-kappaB and IKK requires an upstream kinase complex consisting of TAK1 and adaptor proteins such as TAB1, TAB2, or TAB3...
  39. Sato S, Sanjo H, Takeda K, Ninomiya Tsuji J, Yamamoto M, Kawai T, et al. Essential function for the kinase TAK1 in innate and adaptive immune responses. Nat Immunol. 2005;6:1087-95 pubmed
    Transforming growth factor-beta-activated kinase 1 (TAK1) has been linked to interleukin 1 receptor and tumor necrosis factor receptor signaling...
  40. Uemura N, Kajino T, Sanjo H, Sato S, Akira S, Matsumoto K, et al. TAK1 is a component of the Epstein-Barr virus LMP1 complex and is essential for activation of JNK but not of NF-kappaB. J Biol Chem. 2006;281:7863-72 pubmed
    ..Here we demonstrate that TAK1 mitogen-activated protein kinase kinase kinase and TAK1-binding protein 2 (TAB2), together with TRAF6, are ..
  41. Thiefes A, Wolf A, Doerrie A, Grassl G, Matsumoto K, Autenrieth I, et al. The Yersinia enterocolitica effector YopP inhibits host cell signalling by inactivating the protein kinase TAK1 in the IL-1 signalling pathway. EMBO Rep. 2006;7:838-44 pubmed
    ..YopP inhibits the activity and ubiquitination of a complex consisting of overexpressed TGF-beta-activated kinase 1 (TAK1) and its subunit TAK1-binding protein (TAB)1, but not of MEK kinase 1...
  42. Suzuki S, Singhirunnusorn P, Mori A, Yamaoka S, Kitajima I, Saiki I, et al. Constitutive activation of TAK1 by HTLV-1 tax-dependent overexpression of TAB2 induces activation of JNK-ATF2 but not IKK-NF-kappaB. J Biol Chem. 2007;282:25177-81 pubmed
    ..Transforming growth factor-beta-activated kinase 1 (TAK1) has been shown to play a critical role in these transcription factors...
  43. Windheim M, Lang C, Peggie M, Plater L, Cohen P. Molecular mechanisms involved in the regulation of cytokine production by muramyl dipeptide. Biochem J. 2007;404:179-90 pubmed
    ..We also show that RIP2 induces the activation of the protein kinase TAK1 (transforming-growth-factor-beta-activated kinase-1), that a dominant-negative mutant of TAK1 inhibits RIP2-induced ..
  44. Neil J, Schiemann W. Altered TAB1:I kappaB kinase interaction promotes transforming growth factor beta-mediated nuclear factor-kappaB activation during breast cancer progression. Cancer Res. 2008;68:1462-70 pubmed publisher
    ..factor in their malignant counterparts, 4T1 cells, by inducing assembly of TGF-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1):I kappaB kinase beta (IKK beta) complexes, which led to the stimulation of a TAK1:IKK ..
  45. Lam C, Tan C, Teo Z, Tay C, Phua T, Wu Y, et al. Loss of TAK1 increases cell traction force in a ROS-dependent manner to drive epithelial-mesenchymal transition of cancer cells. Cell Death Dis. 2013;4:e848 pubmed publisher
    ..However, the role of non-canonical TGF?-TAK1 signaling in EMT remains unclear...
  46. Sakurai H, Shigemori N, Hasegawa K, Sugita T. TGF-beta-activated kinase 1 stimulates NF-kappa B activation by an NF-kappa B-inducing kinase-independent mechanism. Biochem Biophys Res Commun. 1998;243:545-9 pubmed
    ..We isolated cDNA for human TGF-beta activated kinase 1 (TAK1), a member of the MAPKKK family, and evaluated its ability to stimulate NF-kappa B activation...
  47. Ahmed N, Zeng M, Sinha I, Polin L, Wei W, Rathinam C, et al. The E3 ligase Itch and deubiquitinase Cyld act together to regulate Tak1 and inflammation. Nat Immunol. 2011;12:1176-83 pubmed publisher
    ..complex sequentially cleaved Lys63-linked ubiquitin chains and catalyzed Lys48-linked ubiquitination on the kinase Tak1 to terminate inflammatory signaling via tumor necrosis factor...
  48. Jiang Z, Ninomiya Tsuji J, Qian Y, Matsumoto K, Li X. Interleukin-1 (IL-1) receptor-associated kinase-dependent IL-1-induced signaling complexes phosphorylate TAK1 and TAB2 at the plasma membrane and activate TAK1 in the cytosol. Mol Cell Biol. 2002;22:7158-67 pubmed
    ..IRAK then brings TRAF6 to TAK1, TAB1, and TAB2, which are preassociated on the membrane before stimulation to form the membrane-associated complex ..
  49. Cheung P, Campbell D, Nebreda A, Cohen P. Feedback control of the protein kinase TAK1 by SAPK2a/p38alpha. EMBO J. 2003;22:5793-805 pubmed
    TAB1, a subunit of the kinase TAK1, was phosphorylated by SAPK2a/p38alpha at Ser423, Thr431 and Ser438 in vitro...
  50. Ishitani T, Takaesu G, Ninomiya Tsuji J, Shibuya H, Gaynor R, Matsumoto K. Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling. EMBO J. 2003;22:6277-88 pubmed
    ..b>TAK1, a MAPKKK, is critical for both IL-1- and TNF-induced activation of the NF-kappaB pathway...
  51. Scholz R, Sidler C, Thali R, Winssinger N, Cheung P, Neumann D. Autoactivation of transforming growth factor beta-activated kinase 1 is a sequential bimolecular process. J Biol Chem. 2010;285:25753-66 pubmed publisher
    Transforming growth factor-beta-activated kinase 1 (TAK1), an MAP3K, is a key player in processing a multitude of inflammatory stimuli. TAK1 autoactivation involves the interplay with TAK1-binding proteins (TAB), e.g...
  52. Frobøse H, Rønn S, Heding P, Mendoza H, Cohen P, Mandrup Poulsen T, et al. Suppressor of cytokine Signaling-3 inhibits interleukin-1 signaling by targeting the TRAF-6/TAK1 complex. Mol Endocrinol. 2006;20:1587-96 pubmed
    ..TRAF)6, and TGFbeta-activated kinase (TAK)1, but not when the MAP3K MAPK/ERK kinase kinase-1 is used instead of TAK1, indicating that the target for SOCS-3 is the TRAF6/TAK1 signaling complex...
  53. Yang Y, Yin C, Pandey A, Abbott D, Sassetti C, Kelliher M. NOD2 pathway activation by MDP or Mycobacterium tuberculosis infection involves the stable polyubiquitination of Rip2. J Biol Chem. 2007;282:36223-9 pubmed
    ..requirement for the E2-conjugating enzyme Ubc13, the E3 ubiquitin ligase Traf6, and the ubiquitin-activated kinase Tak1 in Nod2-mediated NF-kappaB activation...
  54. Singhirunnusorn P, Suzuki S, Kawasaki N, Saiki I, Sakurai H. Critical roles of threonine 187 phosphorylation in cellular stress-induced rapid and transient activation of transforming growth factor-beta-activated kinase 1 (TAK1) in a signaling complex containing TAK1-binding protein TAB1 and TAB2. J Biol Chem. 2005;280:7359-68 pubmed
    Transforming growth factor-beta-activated kinase 1 (TAK1) mitogen-activated protein kinase kinase kinase has been shown to be activated by cellular stresses including tumor necrosis factor-alpha (TNF-alpha)...
  55. Sorrentino A, Thakur N, Grimsby S, Marcusson A, von Bulow V, Schuster N, et al. The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner. Nat Cell Biol. 2008;10:1199-207 pubmed publisher
    ..TGF-beta-associated kinase 1 (TAK1), a member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family, was originally identified as an ..
  56. Sun L, Deng L, Ea C, Xia Z, Chen Z. The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Mol Cell. 2004;14:289-301 pubmed
    ..Here we present evidence that TRAF6 ubiquitin ligase and TAK1 protein kinase mediate IKK activation by BCL10 and MALT1...
  57. Ea C, Deng L, Xia Z, Pineda G, Chen Z. Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Mol Cell. 2006;22:245-57 pubmed
    ..The K377R mutation of RIP1 also prevents the recruitment of TAK1 and IKK complexes to TNF receptor...
  58. Kishimoto K, Matsumoto K, Ninomiya Tsuji J. TAK1 mitogen-activated protein kinase kinase kinase is activated by autophosphorylation within its activation loop. J Biol Chem. 2000;275:7359-64 pubmed
    b>TAK1, a member of the mitogen-activated kinase kinase kinase family, is activated in vivo by various cytokines, including interleukin-1 (IL-1), or when ectopically expressed together with the TAK1-binding protein TAB1...
  59. Takaesu G, Kishida S, Hiyama A, Yamaguchi K, Shibuya H, Irie K, et al. TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway. Mol Cell. 2000;5:649-58 pubmed
    The TAK1 MAPKKK mediates activation of JNK and NF-KB in the IL-1-activated signaling pathway. Here we report the identification of TAB2, a novel intermediate in the IL-1 pathway that functionally links TAK1 to TRAF6...
  60. Li Q, Yan J, Mao A, Li C, Ran Y, Shu H, et al. Tripartite motif 8 (TRIM8) modulates TNF?- and IL-1?-triggered NF-?B activation by targeting TAK1 for K63-linked polyubiquitination. Proc Natl Acad Sci U S A. 2011;108:19341-6 pubmed publisher
    ..Coimmunoprecipitations indicated that TRIM8 interacted with TGF? activated kinase 1 (TAK1), a serine/threonine kinase essential for TNF?- and IL-?-induced NF-?B activation...
  61. Mochida Y, Takeda K, Saitoh M, Nishitoh H, Amagasa T, Ninomiya Tsuji J, et al. ASK1 inhibits interleukin-1-induced NF-kappa B activity through disruption of TRAF6-TAK1 interaction. J Biol Chem. 2000;275:32747-52 pubmed
    ..Here we show that ASK1 directly interacts with transforming growth factor-beta-activated kinase 1 (TAK1), another MAPKKK that has been identified as a signaling intermediate in the interleukin 1 (IL-1)-induced NF-kappaB ..
  62. Takaesu G, Ninomiya Tsuji J, Kishida S, Li X, Stark G, Matsumoto K. Interleukin-1 (IL-1) receptor-associated kinase leads to activation of TAK1 by inducing TAB2 translocation in the IL-1 signaling pathway. Mol Cell Biol. 2001;21:2475-84 pubmed
    ..IL-1 stimulation activates the mitogen-activated protein kinase kinase kinase TAK1, which in turn mediates activation of c-Jun N-terminal kinase and NF-kappaB...
  63. Fan Y, Yu Y, Mao R, Tan X, Xu G, Zhang H, et al. USP4 targets TAK1 to downregulate TNFα-induced NF-κB activation. Cell Death Differ. 2011;18:1547-60 pubmed publisher
    Lys63-linked polyubiquitination of transforming growth factor-β-activated kinase 1 (TAK1) has an important role in tumor necrosis factor-α (TNFα)-induced NF-κB activation...
  64. Lee S, Han S, Kim H, Lee Z. TAK1-dependent activation of AP-1 and c-Jun N-terminal kinase by receptor activator of NF-kappaB. J Biochem Mol Biol. 2002;35:371-6 pubmed
    ..Recently, the association of the MAPK kinase kinase, transforming growth factor-beta-activated kinase 1 (TAK1), with TRAF6 was shown to mediate the IL-1 signaling to NF-kappaB and JNK...
  65. Bottero V, Kerur N, Sadagopan S, Patel K, Sharma Walia N, Chandran B. Phosphorylation and polyubiquitination of transforming growth factor beta-activated kinase 1 are necessary for activation of NF-kappaB by the Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor. J Virol. 2011;85:1980-93 pubmed publisher
    ..In the present work, we show that transforming growth factor ? (TGF-?)-activated kinase 1 (TAK1) is an important player in NF-?B activation induced by vGPCR...
  66. Wu Z, Wong E, Shi Y, Niu J, Chen Z, Miyamoto S, et al. ATM- and NEMO-dependent ELKS ubiquitination coordinates TAK1-mediated IKK activation in response to genotoxic stress. Mol Cell. 2010;40:75-86 pubmed publisher
    ..Here we show that ATM activates the IKK kinase TAK1 in a manner dependent on IKK?/NEMO and ELKS (a protein rich in glutamate, leucine, lysine, and serine)...
  67. Xia Z, Sun L, Chen X, Pineda G, Jiang X, Adhikari A, et al. Direct activation of protein kinases by unanchored polyubiquitin chains. Nature. 2009;461:114-9 pubmed publisher
    ..of UBC13 (also known as UBE2N) and UEV1A (UBE2V1) to catalyse Lys 63-linked polyubiquitination, which activates the TAK1 (also known as MAP3K7) kinase complex...
  68. Wu X, Sun S. Retroviral oncoprotein Tax deregulates NF-kappaB by activating Tak1 and mediating the physical association of Tak1-IKK. EMBO Rep. 2007;8:510-5 pubmed
    ..Here, we show that Tax functions as an intracellular stimulator of an IKK-activating kinase, Tak1 (TGF-beta-activating kinase 1)...