Gene Symbol: Map3k7
Description: mitogen activated protein kinase kinase kinase 7
Alias: Tak1, mitogen-activated protein kinase kinase kinase 7, TGF-beta activated kinase 1
Species: rat
Products:     Map3k7

Top Publications

  1. Bhat N, Shen Q, Fan F. TAK1-mediated induction of nitric oxide synthase gene expression in glial cells. J Neurochem. 2003;87:238-47 pubmed
    ..A common upstream kinase that signals the activation of these pathways is TGFbeta-activated kinase 1 (TAK1), which itself becomes activated in response to cytokines and upon engagement of a class of cell surface receptors ..
  2. Madhavan S, Anghelina M, Sjostrom D, Dossumbekova A, Guttridge D, Agarwal S. Biomechanical signals suppress TAK1 activation to inhibit NF-kappaB transcriptional activation in fibrochondrocytes. J Immunol. 2007;179:6246-54 pubmed
    ..These signals exert their anti-inflammatory effects by inhibiting phosphorylation of TAK1, a critical point where signals generated by IL-1beta, TNF-alpha, and LPS converge to initiate NF-kappaB signaling ..
  3. Zhou K, Enkhjargal B, Xie Z, Sun C, Wu L, Malaguit J, et al. Dihydrolipoic Acid Inhibits Lysosomal Rupture and NLRP3 Through Lysosome-Associated Membrane Protein-1/Calcium/Calmodulin-Dependent Protein Kinase II/TAK1 Pathways After Subarachnoid Hemorrhage in Rat. Stroke. 2018;49:175-183 pubmed publisher
    ..RNA abolished the neuroprotective effects of DHLA and increased the level of phosphorylated CaMKIIα, p-TAK1 (phosphorylated transforming growth factor-β-activated kinase), p-JNK (phosphorylated c-Jun-N-terminal kinase), ..
  4. 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...
  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. Komatsu Y, Shibuya H, Takeda N, Ninomiya Tsuji J, Yasui T, Miyado K, et al. Targeted disruption of the Tab1 gene causes embryonic lethality and defects in cardiovascular and lung morphogenesis. Mech Dev. 2002;119:239-49 pubmed
    ..kinase-1 binding protein-1 (TAB1) was identified as a molecule that activates TGF-beta activated kinase-1 (TAK1)...
  7. Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int Rev Immunol. 2011;30:16-34 pubmed publisher
    ..In this review, we comprehensively review the recent progress in the field of PAMP recognition by PRRs and the signaling pathways activated by PRRs. ..
  8. Weber A, Wasiliew P, Kracht M. Interleukin-1 (IL-1) pathway. Sci Signal. 2010;3:cm1 pubmed publisher
    ..Of note, most intracellular components that participate in the cellular response to IL-1 also mediate responses to other cytokines (IL-18 and IL-33), Toll-like-receptors (TLRs), and many forms of cytotoxic stresses. ..
  9. Johnson G, Nakamura K. The c-jun kinase/stress-activated pathway: regulation, function and role in human disease. Biochim Biophys Acta. 2007;1773:1341-8 pubmed
    ..In this review, we present our current understanding of JNK regulation and their involvement in homeostasis and dysregulation in human disease. ..

More Information


  1. Cuenda A, Rousseau S. p38 MAP-kinases pathway regulation, function and role in human diseases. Biochim Biophys Acta. 2007;1773:1358-75 pubmed
    ..Here we focus on these emergent roles of p38MAPKs and their implication in different pathologies. ..
  2. Wade E, Daniel P, Jenkins Z, McInerney Leo A, Leo P, Morgan T, et al. Mutations in MAP3K7 that Alter the Activity of the TAK1 Signaling Complex Cause Frontometaphyseal Dysplasia. Am J Hum Genet. 2016;99:392-406 pubmed publisher
    ..sequencing in 19 FMD-affected individuals with no identifiable FLNA mutation, we identified mutations in two genes-MAP3K7, encoding transforming growth factor ? (TGF-?)-activated kinase (TAK1), and TAB2, encoding TAK1-associated binding ..
  3. Chang M, Ho F, Wang J, Kang H, Chang Y, Ye Z, et al. AICAR induces cyclooxygenase-2 expression through AMP-activated protein kinase-transforming growth factor-beta-activated kinase 1-p38 mitogen-activated protein kinase signaling pathway. Biochem Pharmacol. 2010;80:1210-20 pubmed publisher
    ..Furthermore, we also found that TAK1 is associated with AMPKalpha2, and this binding requires an interaction between the kinase domains of both ..
  4. Liu W, Chang B, Cramer S, Koty P, Li T, Sun J, et al. Deletion of a small consensus region at 6q15, including the MAP3K7 gene, is significantly associated with high-grade prostate cancers. Clin Cancer Res. 2007;13:5028-33 pubmed
    ..The MAP3K7 gene is one of five genes located in this region. In total, MAP3K7 was deleted in 32% of 95 tumors...
  5. Jadrich J, O Connor M, Coucouvanis E. The TGF beta activated kinase TAK1 regulates vascular development in vivo. Development. 2006;133:1529-41 pubmed
    TGFbeta activated kinase 1 (TAK1) is a MAPKKK that in cell culture systems has been shown to act downstream of a variety of signaling molecules, including TGFbeta...
  6. Watkins S, Jonker L, Arthur H. A direct interaction between TGFbeta activated kinase 1 and the TGFbeta type II receptor: implications for TGFbeta signalling and cardiac hypertrophy. Cardiovasc Res. 2006;69:432-9 pubmed
    Transforming growth factor beta (TGFbeta)-activated kinase 1 (TAK1) is a MAP kinase kinase kinase involved in numerous signalling pathways and is strongly implicated in cardiac hypertrophy and heart failure...
  7. Li M, Katsura K, Nomiyama H, Komaki K, Ninomiya Tsuji J, Matsumoto K, et al. Regulation of the interleukin-1-induced signaling pathways by a novel member of the protein phosphatase 2C family (PP2Cepsilon). J Biol Chem. 2003;278:12013-21 pubmed
    Although TAK1 signaling plays essential roles in eliciting cellular responses to interleukin-1 (IL-1), a proinflammatory cytokine, how the IL-1-TAK1 signaling pathway is positively and negatively regulated remains poorly understood...
  8. Kinugawa K, Jeong M, Bristow M, Long C. Thyroid hormone induces cardiac myocyte hypertrophy in a thyroid hormone receptor alpha1-specific manner that requires TAK1 and p38 mitogen-activated protein kinase. Mol Endocrinol. 2005;19:1618-28 pubmed novel for a nuclear hormone receptor and involves the transforming growth factor beta-activated kinase (TAK1) and p38...
  9. Shim J, Xiao C, Paschal A, Bailey S, Rao P, Hayden M, et al. TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo. Genes Dev. 2005;19:2668-81 pubmed
    TGF-beta-activated kinase 1 (TAK1), a member of the MAPKKK family, is thought to be a key modulator of the inducible transcription factors NF-kappaB and AP-1 and, therefore, plays a crucial role in regulating the genes that mediate ..
  10. Konishi N, Nakamura M, Kishi M, Ishida E, Shimada K, Matsuyoshi S, et al. Genetic mapping of allelic loss on chromosome 6q within heterogeneous prostate carcinoma. Cancer Sci. 2003;94:764-8 pubmed
    ..11 cM on 6q16-21 between markers D6S424 and D6S283. By RT-PCR analysis, the TAK1 gene located at these loci did not correlate with LOH status, indicating that TAK1 is not a target gene in prostate ..
  11. Cuadrado A, Nebreda A. Mechanisms and functions of p38 MAPK signalling. Biochem J. 2010;429:403-17 pubmed publisher
    ..Finally, we discuss how genetic mouse models are facilitating the identification of physiological functions for p38 MAPKs, which may impinge on their eventual use as therapeutic targets. ..
  12. 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 ..
  13. Zhang D, Yan H, Li H, Hao S, Zhuang Z, Liu M, et al. TGFβ-activated Kinase 1 (TAK1) Inhibition by 5Z-7-Oxozeaenol Attenuates Early Brain Injury after Experimental Subarachnoid Hemorrhage. J Biol Chem. 2015;290:19900-9 pubmed publisher
    ..Here we evaluate the role of TGFβ-activated kinase 1 (TAK1), a critical regulator of the NF-κB and MAPK pathways, in early brain injury following SAH...
  14. Liu S, Chen Z. Expanding role of ubiquitination in NF-?B signaling. Cell Res. 2011;21:6-21 pubmed publisher
  15. Vanlangenakker N, Vanden Berghe T, Bogaert P, Laukens B, Zobel K, Deshayes K, et al. cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species production. Cell Death Differ. 2011;18:656-65 pubmed publisher
    ..of RIP1 allows it to bind to the pro-survival kinase transforming growth factor-?-activated kinase 1 (TAK1) which prevents it from activating caspase-8-dependent death, a process reverted by the de-ubiquitinase CYLD...
  16. Moriguchi M, Yamada M, Miake Y, Yanagisawa T. Immunolocalization of TAK1, TAB1, and p38 in the developing rat molar. Anat Sci Int. 2011;86:69-77 pubmed publisher
    ..However, only a few studies have focused on the non-Smad pathway in tooth development. TGF-?-activated kinase 1 (TAK1) is activated by TGF-? or BMP and binds to TAK1-binding protein (TAB1), activating p38 or c-Jun N-terminal kinase (..
  17. 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...
  18. Katsura H, Obata K, Miyoshi K, Kondo T, Yamanaka H, Kobayashi K, et al. Transforming growth factor-activated kinase 1 induced in spinal astrocytes contributes to mechanical hypersensitivity after nerve injury. Glia. 2008;56:723-33 pubmed publisher
    ..Transforming growth factor-activated kinase 1 (TAK1), a member of the MAPK kinase kinase family, is indispensable for the activation of c-Jun N-terminal kinase (JNK) ..
  19. Kaur S, Wang F, Venkatraman M, Arsura M. X-linked inhibitor of apoptosis (XIAP) inhibits c-Jun N-terminal kinase 1 (JNK1) activation by transforming growth factor beta1 (TGF-beta1) through ubiquitin-mediated proteosomal degradation of the TGF-beta1-activated kinase 1 (TAK1). J Biol Chem. 2005;280:38599-608 pubmed
    ..of XIAP gene expression in response to TGF-beta1 treatment and forms a TGF-beta1-inducible complex with TAK1. Furthermore, we show that the RING domain of XIAP mediates TAK1 polyubiquitination, which then targets this ..
  20. Zhong S, Xu J, Li P, Tsukamoto H. Caveosomal oxidative stress causes Src-p21ras activation and lysine 63 TRAF6 protein polyubiquitination in iron-induced M1 hepatic macrophage activation. J Biol Chem. 2012;287:32078-84 pubmed publisher
    ..IKK) and NF-?B in HM via activation and interaction of p21(ras), transforming growth factor ?-activated kinase-1 (TAK1), and phosphatidylinositol 3-kinase (PI3K) in caveosomes...
  21. Matsumoto Ida M, Takimoto Y, Aoyama T, Akao M, Takeda T, Kita T. Activation of TGF-beta1-TAK1-p38 MAPK pathway in spared cardiomyocytes is involved in left ventricular remodeling after myocardial infarction in rats. Am J Physiol Heart Circ Physiol. 2006;290:H709-15 pubmed
    ..myocardial gene expression, resulting in myocyte hypertrophy, through activation of TGF-beta-activated kinase (TAK1), a member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family...
  22. Tian Q, Xiao Q, Yu W, Gu M, Zhao N, Lü Y. The inhibition of transforming growth factor beta-activated kinase 1 contributed to neuroprotection via inflammatory reaction in pilocarpine-induced rats with epilepsy. Neuroscience. 2016;325:111-23 pubmed publisher
    ..necrosis factor-α receptor-associated factor-6 (TRAF6), transforming growth factor beta-activated kinase 1 (TAK1), which are the key elements of TGFβ-associated inflammation, is still unclear in epilepsy...
  23. Yang B, Li W, Zheng Q, Qin T, Wang K, Li J, et al. Transforming growth factor β-activated kinase 1 negatively regulates interleukin-1α-induced stromal-derived factor-1 expression in vascular smooth muscle cells. Biochem Biophys Res Commun. 2015;463:130-6 pubmed publisher
    ..and SDF-1 was significantly potentiated by knockdown of transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of IKKβ signaling...
  24. Chen N, Debnath J. I?B kinase complex (IKK) triggers detachment-induced autophagy in mammary epithelial cells independently of the PI3K-AKT-MTORC1 pathway. Autophagy. 2013;9:1214-27 pubmed publisher
    ..Instead, inhibition of IKK, as well as its upstream regulator, MAP3K7/TAK1, significantly attenuates detachment-induced autophagy in MECs...
  25. Li K, Yang B, Zhao C. Transforming growth factor-?-activated kinase 1 enhances H2O2-induced apoptosis independently of reactive oxygen species in cardiomyocytes. J Cardiovasc Med (Hagerstown). 2014;15:565-71 pubmed publisher
    ..we investigated the effects of reactive oxygen species (ROS) and transforming growth factor-?-activated kinase 1 (TAK1) on HSP70-regulated cardiomyocyte protection...
  26. Chen Z, Shen X, Shen F, Zhong W, Wu H, Liu S, et al. TAK1 activates AMPK-dependent cell death pathway in hydrogen peroxide-treated cardiomyocytes, inhibited by heat shock protein-70. Mol Cell Biochem. 2013;377:35-44 pubmed publisher
    ..We here proposed that transforming growth factor-?-activating kinase 1 (TAK1) might be the upstream kinase for AMPK activation by H2O2...
  27. Jiang Z, Mak T, Sen G, Li X. Toll-like receptor 3-mediated activation of NF-kappaB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing IFN-beta. Proc Natl Acad Sci U S A. 2004;101:3533-8 pubmed
    ..Instead, TRAF6, TAK1, and TAB2 are recruited to TLR3 on poly(I.C) stimulation...
  28. Xie M, Zhang D, Dyck J, Li Y, Zhang H, Morishima M, et al. A pivotal role for endogenous TGF-beta-activated kinase-1 in the LKB1/AMP-activated protein kinase energy-sensor pathway. Proc Natl Acad Sci U S A. 2006;103:17378-83 pubmed
    TGF-beta-activated kinase-1 (TAK1), also known as MAPKK kinase-7 (MAP3K7), is a candidate effector of multiple circuits in cardiac biology and disease...
  29. Frazier D, Wilson A, Dougherty C, Li H, Bishopric N, Webster K. PKC-alpha and TAK-1 are intermediates in the activation of c-Jun NH2-terminal kinase by hypoxia-reoxygenation. Am J Physiol Heart Circ Physiol. 2007;292:H1675-84 pubmed
    ..These results identify two new components, PKC and TAK-1, that have not been previously described in this signaling pathway. ..
  30. Ding L, Takebayashi H, Watanabe K, Ohtsuki T, Tanaka K, Nabeshima Y, et al. Short-term lineage analysis of dorsally derived Olig3 cells in the developing spinal cord. Dev Dyn. 2005;234:622-32 pubmed
    ..Dorsal midline cells were also LacZ-positive during development. These findings suggest that dorsal Olig3 cells contribute to dorsal midline cells and commissural interneurons at intermediate and ventral levels. ..
  31. 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...
  32. Moriguchi T, Kuroyanagi N, Yamaguchi K, Gotoh Y, Irie K, Kano T, et al. A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3. J Biol Chem. 1996;271:13675-9 pubmed
    ..protein kinase superfamily and could be demonstrated to be phosphorylated and activated in vitro by TAK1, a recently identified MAPKK kinase. MKK3 was also shown to be a good substrate for TAK1 in vitro...
  33. 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 ..
  34. Verstrepen L, Bekaert T, Chau T, Tavernier J, Chariot A, Beyaert R. TLR-4, IL-1R and TNF-R signaling to NF-kappaB: variations on a common theme. Cell Mol Life Sci. 2008;65:2964-78 pubmed publisher
    ..In this review, we will discuss our current knowledge of NF-kappaB signaling in response to TLR-4, TNF-R and IL-1R stimulation, with a special focus on the similarities and dissimilarities among these pathways. ..