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Apoptosis

pp 1–18 | Cite as

TAK1 mediates convergence of cellular signals for death and survival

  • Sabreena Aashaq
  • Asiya Batool
  • Khurshid I. Andrabi
Review
  • 139 Downloads

Abstract

TGF-β activated kinase 1, a MAPK kinase kinase family serine threonine kinase has been implicated in regulating diverse range of cellular processes that include embryonic development, differentiation, autophagy, apoptosis and cell survival. TAK1 along with its binding partners TAB1, TAB2 and TAB3 displays a complex pattern of regulation that includes serious crosstalk with major signaling pathways including the C-Jun N-terminal kinase (JNK), p38 MAPK, and I-kappa B kinase complex (IKK) involved in establishing cellular commitments for death and survival. This review also highlights how TAK1 orchestrates regulation of energy homeostasis via AMPK and its emerging role in influencing mTORC1 pathway to regulate death or survival in tandem.

Keywords

Apoptosis Autophagy Cytokine Inflammatory Smad 

Notes

Acknowledgements

Infrastructure grants in favour of Khurshid I. Andrabi under DST-SERB are gratefully acknowledged. Individual fellowships in favour of Sabreena Aashaq (23-12/2012) from University Grant Commission (UGC) New Delhi, India, and Asiya Batool (140150/2014) from Department of Science and Technology are highly acknowledged.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this paper.

References

  1. 1.
    Massagué J, Blain SW, Lo RS (2000) TGFbeta signaling in growth control, cancer, and heritable disorders. Cell 103:295–309CrossRefGoogle Scholar
  2. 2.
    Derynck R, Zhang YE (2003) Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425:577–584.  https://doi.org/10.1038/nature02006 CrossRefGoogle Scholar
  3. 3.
    Hartsough MT, Mulder KM (1995) Transforming growth factor beta activation of p44mapk in proliferating cultures of epithelial cells. J Biol Chem 270:7117–7124CrossRefGoogle Scholar
  4. 4.
    Heldin CH, Miyazono K, ten Dijke P (1997) TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 390:465–471.  https://doi.org/10.1038/37284 CrossRefPubMedGoogle Scholar
  5. 5.
    Massagué J (1998) TGF-beta signal transduction. Annu Rev Biochem 67:753–791.  https://doi.org/10.1146/annurev.biochem.67.1.753 CrossRefPubMedGoogle Scholar
  6. 6.
    Massagué J (2000) How cells read TGF-beta signals. Nat Rev Mol Cell Biol 1:169–178.  https://doi.org/10.1038/35043051 CrossRefPubMedGoogle Scholar
  7. 7.
    Moustakas A, Heldin C-H (2005) Non-Smad TGF-beta signals. J Cell Sci 118:3573–3584.  https://doi.org/10.1242/jcs.02554 CrossRefPubMedGoogle Scholar
  8. 8.
    Zhang YE (2009) Non-Smad pathways in TGF-beta signaling. Cell Res 19:128–139.  https://doi.org/10.1038/cr.2008.328 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Mucsi I, Skorecki KL, Goldberg HJ (1996) Extracellular signal-regulated kinase and the small GTP-binding protein, Rac, contribute to the effects of transforming growth factor-beta1 on gene expression. J Biol Chem 271:16567–16572CrossRefGoogle Scholar
  10. 10.
    Hanafusa H, Ninomiya-Tsuji J, Masuyama N et al (1999) Involvement of the p38 mitogen-activated protein kinase pathway in transforming growth factor-beta-induced gene expression. J Biol Chem 274:27161–27167CrossRefGoogle Scholar
  11. 11.
    Rodríguez-Barbero A, Obreo J, Yuste L et al (2002) Transforming growth factor-beta1 induces collagen synthesis and accumulation via p38 mitogen-activated protein kinase (MAPK) pathway in cultured L(6)E(9) myoblasts. FEBS Lett 513:282–288CrossRefGoogle Scholar
  12. 12.
    Atfi A, Djelloul S, Chastre E et al (1997) Evidence for a role of Rho-like GTPases and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in transforming growth factor beta-mediated signaling. J Biol Chem 272:1429–1432CrossRefGoogle Scholar
  13. 13.
    Yue J, Sun B, Liu G, Mulder KM (2004) Requirement of TGF-beta receptor-dependent activation of c-Jun N-terminal kinases (JNKs)/stress-activated protein kinases (Sapks) for TGF-beta up-regulation of the urokinase-type plasminogen activator receptor. J Cell Physiol 199:284–292.  https://doi.org/10.1002/jcp.10469 CrossRefPubMedGoogle Scholar
  14. 14.
    Bakin AV, Tomlinson AK, Bhowmick NA et al (2000) Phosphatidylinositol 3-kinase function is required for transforming growth factor beta-mediated epithelial to mesenchymal transition and cell migration. J Biol Chem 275:36803–36810.  https://doi.org/10.1074/jbc.M005912200 CrossRefPubMedGoogle Scholar
  15. 15.
    Ding Y, Kim JK, Kim SI et al (2010) TGF-{beta}1 protects against mesangial cell apoptosis via induction of autophagy. J Biol Chem 285:37909–37919.  https://doi.org/10.1074/jbc.M109.093724 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Edlund S, Landström M, Heldin C-H, Aspenström P (2002) Transforming growth factor-beta-induced mobilization of actin cytoskeleton requires signaling by small GTPases Cdc42 and RhoA. Mol Biol Cell 13:902–914.  https://doi.org/10.1091/mbc.01-08-0398 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Bhowmick NA, Ghiassi M, Bakin A et al (2001) Transforming growth factor-beta1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism. Mol Biol Cell 12:27–36.  https://doi.org/10.1091/mbc.12.1.27 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Ono K, Ohtomo T, Ninomiya-Tsuji J, Tsuchiya M (2003) A dominant negative TAK1 inhibits cellular fibrotic responses induced by TGF-beta. Biochem Biophys Res Commun 307:332–337CrossRefGoogle Scholar
  19. 19.
    Kim SI, Kwak JH, Zachariah M et al (2007) TGF-beta-activated kinase 1 and TAK1-binding protein 1 cooperate to mediate TGF-beta1-induced MKK3-p38 MAPK activation and stimulation of type I collagen. Am J Physiol Renal Physiol 292:F1471–F1478.  https://doi.org/10.1152/ajprenal.00485.2006 CrossRefPubMedGoogle Scholar
  20. 20.
    Hocevar BA, Prunier C, Howe PH (2005) Disabled-2 (Dab2) mediates transforming growth factor beta (TGFbeta)-stimulated fibronectin synthesis through TGFbeta-activated kinase 1 and activation of the JNK pathway. J Biol Chem 280:25920–25927.  https://doi.org/10.1074/jbc.M501150200 CrossRefPubMedGoogle Scholar
  21. 21.
    Akira S (2003) Toll-like receptor signaling. J Biol Chem 278:38105–38108.  https://doi.org/10.1074/jbc.R300028200 CrossRefPubMedGoogle Scholar
  22. 22.
    Yamaguchi K, Shirakabe K, Shibuya H et al (1995) Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction. Science 270:2008–2011CrossRefGoogle Scholar
  23. 23.
    Shibuya H, Yamaguchi K, Shirakabe K et al (1996) TAB1: an activator of the TAK1 MAPKKK in TGF-beta signal transduction. Science 272:1179–1182CrossRefGoogle Scholar
  24. 24.
    Irie T, Muta T, Takeshige K (2000) TAK1 mediates an activation signal from toll-like receptor(s) to nuclear factor-kappaB in lipopolysaccharide-stimulated macrophages. FEBS Lett 467:160–164CrossRefGoogle Scholar
  25. 25.
    Ninomiya-Tsuji J, Kishimoto K, Hiyama A et al (1999) The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature 398:252–256.  https://doi.org/10.1038/18465 CrossRefGoogle Scholar
  26. 26.
    Sakurai H, Suzuki S, Kawasaki N et al (2003) Tumor necrosis factor-alpha-induced IKK phosphorylation of NF-kappaB p65 on serine 536 is mediated through the TRAF2, TRAF5, and TAK1 signaling pathway. J Biol Chem 278:36916–36923.  https://doi.org/10.1074/jbc.M301598200 CrossRefPubMedGoogle Scholar
  27. 27.
    Shirakabe K, Yamaguchi K, Shibuya H et al (1997) TAK1 mediates the ceramide signaling to stress-activated protein kinase/c-Jun N-terminal kinase. J Biol Chem 272:8141–8144CrossRefGoogle Scholar
  28. 28.
    Shim J-H, Xiao C, Paschal AE et al (2005) TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo. Genes Dev 19:2668–2681.  https://doi.org/10.1101/gad.1360605 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Smit L, Baas A, Kuipers J et al (2004) Wnt activates the Tak1/Nemo-like kinase pathway. J Biol Chem 279:17232–17240.  https://doi.org/10.1074/jbc.M307801200 CrossRefPubMedGoogle Scholar
  30. 30.
    Dowdy SC, Mariani A, Janknecht R (2003) HER2/Neu- and TAK1-mediated up-regulation of the transforming growth factor beta inhibitor Smad7 via the ETS protein ER81. J Biol Chem 278:44377–44384.  https://doi.org/10.1074/jbc.M307202200 CrossRefPubMedGoogle Scholar
  31. 31.
    Hoffmann A, Preobrazhenska O, Wodarczyk C et al (2005) Transforming growth factor-beta-activated kinase-1 (TAK1), a MAP3K, interacts with Smad proteins and interferes with osteogenesis in murine mesenchymal progenitors. J Biol Chem 280:27271–27283.  https://doi.org/10.1074/jbc.M503368200 CrossRefPubMedGoogle Scholar
  32. 32.
    Sano Y, Harada J, Tashiro S et al (1999) ATF-2 is a common nuclear target of Smad and TAK1 pathways in transforming growth factor-beta signaling. J Biol Chem 274:8949–8957CrossRefGoogle Scholar
  33. 33.
    Abécassis L, Rogier E, Vazquez A et al (2004) Evidence for a role of MSK1 in transforming growth factor-beta-mediated responses through p38alpha and Smad signaling pathways. J Biol Chem 279:30474–30479.  https://doi.org/10.1074/jbc.M403294200 CrossRefPubMedGoogle Scholar
  34. 34.
    Sorrentino A, Thakur N, Grimsby S et al (2008) The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner. Nat Cell Biol 10:1199–1207.  https://doi.org/10.1038/ncb1780 CrossRefPubMedGoogle Scholar
  35. 35.
    Sayama K, Hanakawa Y, Nagai H et al (2006) Transforming growth factor-beta-activated kinase 1 is essential for differentiation and the prevention of apoptosis in epidermis. J Biol Chem 281:22013–22020.  https://doi.org/10.1074/jbc.M601065200 CrossRefPubMedGoogle Scholar
  36. 36.
    Tan SH, Pal M, Tan MJ et al (2009) Regulation of cell proliferation and migration by TAK1 via transcriptional control of von Hippel-Lindau tumor suppressor. J Biol Chem 284:18047–18058.  https://doi.org/10.1074/jbc.M109.002691 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Xie M, Zhang D, Dyck JRB et al (2006) A pivotal role for endogenous TGF-beta-activated kinase-1 in the LKB1/AMP-activated protein kinase energy-sensor pathway. Proc Natl Acad Sci USA 103:17378–17383.  https://doi.org/10.1073/pnas.0604708103 CrossRefPubMedGoogle Scholar
  38. 38.
    Sakurai H, Miyoshi H, Mizukami J, Sugita T (2000) Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1. FEBS Lett 474:141–145CrossRefGoogle Scholar
  39. 39.
    Ishitani T, Takaesu G, Ninomiya-Tsuji J et al (2003) Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling. EMBO J 22:6277–6288.  https://doi.org/10.1093/emboj/cdg605 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Cheung PCF, Nebreda AR, Cohen P (2004) TAB3, a new binding partner of the protein kinase TAK1. Biochem J 378:27–34.  https://doi.org/10.1042/BJ20031794 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Kim SI, Kwak JH, Na H-J et al (2009) Transforming growth factor-beta (TGF-beta1) activates TAK1 via TAB1-mediated autophosphorylation, independent of TGF-beta receptor kinase activity in mesangial cells. J Biol Chem 284:22285–22296.  https://doi.org/10.1074/jbc.M109.007146 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Ono K, Ohtomo T, Sato S et al (2001) An evolutionarily conserved motif in the TAB1 C-terminal region is necessary for interaction with and activation of TAK1 MAPKKK. J Biol Chem 276:24396–24400.  https://doi.org/10.1074/jbc.M102631200 CrossRefPubMedGoogle Scholar
  43. 43.
    Kishimoto K, Matsumoto K, Ninomiya-Tsuji J (2000) TAK1 mitogen-activated protein kinase kinase kinase is activated by autophosphorylation within its activation loop. J Biol Chem 275:7359–7364CrossRefGoogle Scholar
  44. 44.
    Singhirunnusorn P, Suzuki S, Kawasaki N et al (2005) 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 280:7359–7368.  https://doi.org/10.1074/jbc.M407537200 CrossRefPubMedGoogle Scholar
  45. 45.
    Inagaki M, Omori E, Kim J-Y et al (2008) TAK1-binding protein 1, TAB1, mediates osmotic stress-induced TAK1 activation but is dispensable for TAK1-mediated cytokine signaling. J Biol Chem 283:33080–33086.  https://doi.org/10.1074/jbc.M807574200 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Komatsu Y, Shibuya H, Takeda N et al (2002) Targeted disruption of the Table 1 gene causes embryonic lethality and defects in cardiovascular and lung morphogenesis. Mech Dev 119:239–249CrossRefGoogle Scholar
  47. 47.
    Sanjo H, Takeda K, Tsujimura T et al (2003) TAB2 is essential for prevention of apoptosis in fetal liver but not for interleukin-1 signaling. Mol Cell Biol 23:1231–1238CrossRefGoogle Scholar
  48. 48.
    Kishida S, Sanjo H, Akira S et al (2005) TAK1-binding protein 2 facilitates ubiquitination of TRAF6 and assembly of TRAF6 with IKK in the IL-1 signaling pathway. Genes Cells Devoted Mol Cell Mech 10:447–454.  https://doi.org/10.1111/j.1365-2443.2005.00852.x CrossRefGoogle Scholar
  49. 49.
    Kanayama A, Seth RB, Sun L et al (2004) TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains. Mol Cell 15:535–548.  https://doi.org/10.1016/j.molcel.2004.08.008 CrossRefPubMedGoogle Scholar
  50. 50.
    Holtmann H, Enninga J, Kalble S et al (2001) The MAPK kinase kinase TAK1 plays a central role in coupling the interleukin-1 receptor to both transcriptional and RNA-targeted mechanisms of gene regulation. J Biol Chem 276:3508–3516.  https://doi.org/10.1074/jbc.M004376200 CrossRefPubMedGoogle Scholar
  51. 51.
    Sakurai H, Nishi A, Sato N et al (2002) 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 297:1277–1281CrossRefGoogle Scholar
  52. 52.
    Takaesu G, Kishida S, Hiyama A et al (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 5:649–658CrossRefGoogle Scholar
  53. 53.
    Wang C, Deng L, Hong M et al (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412:346–351.  https://doi.org/10.1038/35085597 CrossRefGoogle Scholar
  54. 54.
    Ea C-K, Deng L, Xia Z-P et al (2006) Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Mol Cell 22:245–257.  https://doi.org/10.1016/j.molcel.2006.03.026 CrossRefPubMedGoogle Scholar
  55. 55.
    Sicheri F, Kuriyan J (1997) Structures of Src-family tyrosine kinases. Curr Opin Struct Biol 7:777–785CrossRefGoogle Scholar
  56. 56.
    Hanks SK, Quinn AM, Hunter T (1988) The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 241:42–52CrossRefGoogle Scholar
  57. 57.
    Brown K, Vial SCM, Dedi N et al (2005) Structural basis for the interaction of TAK1 kinase with its activating protein TAB1. J Mol Biol 354:1013–1020.  https://doi.org/10.1016/j.jmb.2005.09.098 CrossRefPubMedGoogle Scholar
  58. 58.
    Pathak S, Borodkin VS, Albarbarawi O et al (2012) O-glcNAcylation of TAB1 modulates TAK1-mediated cytokine release. EMBO J 31:1394–1404.  https://doi.org/10.1038/emboj.2012.8 CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Chen YG, Hata A, Lo RS et al (1998) Determinants of specificity in TGF-beta signal transduction. Genes Dev 12:2144–2152CrossRefGoogle Scholar
  60. 60.
    Wu G, Chen YG, Ozdamar B et al (2000) Structural basis of Smad2 recognition by the Smad anchor for receptor activation. Science 287:92–97CrossRefGoogle Scholar
  61. 61.
    Reinstein E, Ciechanover A (2006) Narrative review: protein degradation and human diseases: the ubiquitin connection. Ann Intern Med 145:676–684CrossRefGoogle Scholar
  62. 62.
    Yamashita M, Fatyol K, Jin C et al (2008) TRAF6 mediates Smad-independent activation of JNK and p38 by TGF-beta. Mol Cell 31:918–924.  https://doi.org/10.1016/j.molcel.2008.09.002 CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Mu Y, Sundar R, Thakur N et al (2011) TRAF6 ubiquitinates TGFβ type I receptor to promote its cleavage and nuclear translocation in cancer. Nat Commun 2:330.  https://doi.org/10.1038/ncomms1332 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Fan Y, Yu Y, Shi Y et al (2010) 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 285:5347–5360.  https://doi.org/10.1074/jbc.M109.076976 CrossRefPubMedGoogle Scholar
  65. 65.
    Fan Y, Yu Y, Mao R et al (2011) TAK1 Lys-158 but not Lys-209 is required for IL-1β-induced Lys63-linked TAK1 polyubiquitination and IKK/NF-κB activation. Cell Signal 23:660–665.  https://doi.org/10.1016/j.cellsig.2010.11.017 CrossRefPubMedGoogle Scholar
  66. 66.
    Mao R, Fan Y, Mou Y et al (2011) TAK1 lysine 158 is required for TGF-β-induced TRAF6-mediated Smad-independent IKK/NF-κB and JNK/AP-1 activation. Cell Signal 23:222–227.  https://doi.org/10.1016/j.cellsig.2010.09.006 CrossRefPubMedGoogle Scholar
  67. 67.
    Sato S, Sanjo H, Takeda K et al (2005) Essential function for the kinase TAK1 in innate and adaptive immune responses. Nat Immunol 6:1087–1095.  https://doi.org/10.1038/ni1255 CrossRefPubMedGoogle Scholar
  68. 68.
    Qin J, Jiang Z, Qian Y et al (2004) IRAK4 kinase activity is redundant for interleukin-1 (IL-1) receptor-associated kinase phosphorylation and IL-1 responsiveness. J Biol Chem 279:26748–26753.  https://doi.org/10.1074/jbc.M400785200 CrossRefPubMedGoogle Scholar
  69. 69.
    Beutler B (2004) Inferences, questions and possibilities in Toll-like receptor signalling. Nature 430:257–263.  https://doi.org/10.1038/nature02761 CrossRefPubMedGoogle Scholar
  70. 70.
    Arend WP (2002) The balance between IL-1 and IL-1Ra in disease. Cytokine Growth Factor Rev 13:323–340CrossRefGoogle Scholar
  71. 71.
    Zheng CF, Guan KL (1994) Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues. EMBO J 13:1123–1131CrossRefGoogle Scholar
  72. 72.
    Johnson LN, Noble ME, Owen DJ (1996) Active and inactive protein kinases: structural basis for regulation. Cell 85:149–158CrossRefGoogle Scholar
  73. 73.
    Delhase M, Hayakawa M, Chen Y, Karin M (1999) Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation. Science 284:309–313CrossRefGoogle Scholar
  74. 74.
    Mercurio F, Zhu H, Murray BW et al (1997) IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation. Science 278:860–866CrossRefGoogle Scholar
  75. 75.
    Scholz R, Sidler CL, Thali RF et al (2010) Autoactivation of transforming growth factor beta-activated kinase 1 is a sequential bimolecular process. J Biol Chem 285:25753–25766.  https://doi.org/10.1074/jbc.M109.093468 CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Yu Y, Ge N, Xie M et al (2008) 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 283:24497–24505.  https://doi.org/10.1074/jbc.M802825200 CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Kim SI, Kwak JH, Wang L, Choi ME (2008) Protein phosphatase 2A is a negative regulator of transforming growth factor-beta1-induced TAK1 activation in mesangial cells. J Biol Chem 283:10753–10763.  https://doi.org/10.1074/jbc.M801263200 CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Prickett TD, Ninomiya-Tsuji J, Broglie P et al (2008) TAB4 stimulates TAK1-TAB1 phosphorylation and binds polyubiquitin to direct signaling to NF-kappaB. J Biol Chem 283:19245–19254.  https://doi.org/10.1074/jbc.M800943200 CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Kobayashi Y, Mizoguchi T, Take I et al (2005) Prostaglandin E2 enhances osteoclastic differentiation of precursor cells through protein kinase A-dependent phosphorylation of TAK1. J Biol Chem 280:11395–11403.  https://doi.org/10.1074/jbc.M411189200 CrossRefPubMedGoogle Scholar
  80. 80.
    Pearson G, Robinson F, Beers Gibson T et al (2001) Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 22:153–183.  https://doi.org/10.1210/edrv.22.2.0428 CrossRefPubMedGoogle Scholar
  81. 81.
    Siow YL, Kalmar GB, Sanghera JS et al (1997) Identification of two essential phosphorylated threonine residues in the catalytic domain of Mekk1. Indirect activation by Pak3 and protein kinase C. J Biol Chem 272:7586–7594CrossRefGoogle Scholar
  82. 82.
    Posas F, Saito H (1998) Activation of the yeast SSK2 MAP kinase kinase kinase by the SSK1 two-component response regulator. EMBO J 17:1385–1394.  https://doi.org/10.1093/emboj/17.5.1385 CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Deak JC, Templeton DJ (1997) Regulation of the activity of MEK kinase 1 (MEKK1) by autophosphorylation within the kinase activation domain. Biochem J 322(Pt 1):185–192CrossRefGoogle Scholar
  84. 84.
    English JM, Vanderbilt CA, Xu S et al (1995) Isolation of MEK5 and differential expression of alternatively spliced forms. J Biol Chem 270:28897–28902CrossRefGoogle Scholar
  85. 85.
    Yao Z, Zhou G, Wang XS et al (1999) A novel human STE20-related protein kinase, HGK, that specifically activates the c-Jun N-terminal kinase signaling pathway. J Biol Chem 274:2118–2125CrossRefGoogle Scholar
  86. 86.
    Ouyang C, Nie L, Gu M et al (2014) Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) activation requires phosphorylation of serine 412 by protein kinase A catalytic subunit α (PKACα) and X-linked protein kinase (PRKX). J Biol Chem 289:24226–24237.  https://doi.org/10.1074/jbc.M114.559963 CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Hanada M, Ninomiya-Tsuji J, Komaki K et al (2001) Regulation of the TAK1 signaling pathway by protein phosphatase 2C. J Biol Chem 276:5753–5759.  https://doi.org/10.1074/jbc.M007773200 CrossRefPubMedGoogle Scholar
  88. 88.
    Li MG, Katsura K, Nomiyama H et al (2003) Regulation of the interleukin-1-induced signaling pathways by a novel member of the protein phosphatase 2C family (PP2Cepsilon). J Biol Chem 278:12013–12021.  https://doi.org/10.1074/jbc.M211474200 CrossRefPubMedGoogle Scholar
  89. 89.
    Kajino T, Ren H, Iemura S-I et al (2006) Protein phosphatase 6 down-regulates TAK1 kinase activation in the IL-1 signaling pathway. J Biol Chem 281:39891–39896.  https://doi.org/10.1074/jbc.M608155200 CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Broglie P, Matsumoto K, Akira S et al (2010) 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 285:2333–2339.  https://doi.org/10.1074/jbc.M109.090522 CrossRefPubMedGoogle Scholar
  91. 91.
    Takaesu G, Ninomiya-Tsuji J, Kishida S et al (2001) 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 21:2475–2484.  https://doi.org/10.1128/MCB.21.7.2475-2484.2001 CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Cheung PCF, Campbell DG, Nebreda AR, Cohen P (2003) Feedback control of the protein kinase TAK1 by SAPK2a/p38alpha. EMBO J 22:5793–5805.  https://doi.org/10.1093/emboj/cdg552 CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Courtois G (2008) Tumor suppressor CYLD: negative regulation of NF-kappaB signaling and more. Cell Mol Life Sci CMLS 65:1123–1132.  https://doi.org/10.1007/s00018-007-7465-4 CrossRefPubMedGoogle Scholar
  94. 94.
    Ahmed N, Zeng M, Sinha I et al (2011) The E3 ligase Itch and deubiquitinase Cyld act together to regulate Tak1 and inflammation. Nat Immunol 12:1176–1183.  https://doi.org/10.1038/ni.2157 CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Fan Y, Shi Y, Liu S et al (2012) Lys48-linked TAK1 polyubiquitination at lysine-72 downregulates TNFα-induced NF-κB activation via mediating TAK1 degradation. Cell Signal 24:1381–1389.  https://doi.org/10.1016/j.cellsig.2012.02.017 CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Ruland J (2011) Return to homeostasis: downregulation of NF-κB responses. Nat Immunol 12:709–714.  https://doi.org/10.1038/ni.2055 CrossRefPubMedGoogle Scholar
  97. 97.
    Fan Y-H, Yu Y, Mao R-F et al (2011) USP4 targets TAK1 to downregulate TNFα-induced NF-κB activation. Cell Death Differ 18:1547–1560.  https://doi.org/10.1038/cdd.2011.11 CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Beg ZH, Allmann DW, Gibson DM (1973) Modulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity with cAMP and wth protein fractions of rat liver cytosol. Biochem Biophys Res Commun 54:1362–1369CrossRefGoogle Scholar
  99. 99.
    Carling D, Zammit VA, Hardie DG (1987) A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis. FEBS Lett 223:217–222CrossRefGoogle Scholar
  100. 100.
    Carlson CA, Kim KH (1974) Regulation of hepatic acetyl coenzyme A carboxylase by phosphorylation and dephosphorylation. Arch Biochem Biophys 164:478–489CrossRefGoogle Scholar
  101. 101.
    Kemp BE, Stapleton D, Campbell DJ et al (2003) AMP-activated protein kinase, super metabolic regulator. Biochem Soc Trans 31:162–168.  https://doi.org/10.1042/bst0310162 CrossRefPubMedGoogle Scholar
  102. 102.
    Kahn BB, Alquier T, Carling D, Hardie DG (2005) AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 1:15–25.  https://doi.org/10.1016/j.cmet.2004.12.003 CrossRefGoogle Scholar
  103. 103.
    Gowans GJ, Hawley SA, Ross FA, Hardie DG (2013) AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation. Cell Metab 18:556–566.  https://doi.org/10.1016/j.cmet.2013.08.019 CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Hardie DG, Carling D (1997) The AMP-activated protein kinase–fuel gauge of the mammalian cell? Eur J Biochem 246:259–273CrossRefGoogle Scholar
  105. 105.
    Hardie DG, Carling D, Carlson M (1998) The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell? Annu Rev Biochem 67:821–855.  https://doi.org/10.1146/annurev.biochem.67.1.821 CrossRefPubMedGoogle Scholar
  106. 106.
    Hardie DG, Salt IP, Hawley SA, Davies SP (1999) AMP-activated protein kinase: an ultrasensitive system for monitoring cellular energy charge. Biochem J 338(Pt 3):717–722CrossRefGoogle Scholar
  107. 107.
    Xiao B, Sanders MJ, Underwood E et al (2011) Structure of mammalian AMPK and its regulation by ADP. Nature 472:230–233.  https://doi.org/10.1038/nature09932 CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Davies SP, Helps NR, Cohen PT, Hardie DG (1995) 5′-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C alpha and native bovine protein phosphatase-2AC. FEBS Lett 377:421–425.  https://doi.org/10.1016/0014-5793(95)01368-7 CrossRefGoogle Scholar
  109. 109.
    Oakhill JS, Steel R, Chen Z-P et al (2011) AMPK is a direct adenylate charge-regulated protein kinase. Science 332:1433–1435.  https://doi.org/10.1126/science.1200094 CrossRefPubMedGoogle Scholar
  110. 110.
    Hawley SA, Selbert MA, Goldstein EG et al (1995) 5′-AMP activates the AMP-activated protein kinase cascade, and Ca2+/calmodulin activates the calmodulin-dependent protein kinase I cascade, via three independent mechanisms. J Biol Chem 270:27186–27191CrossRefGoogle Scholar
  111. 111.
    Hawley SA, Davison M, Woods A et al (1996) Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase. J Biol Chem 271:27879–27887CrossRefGoogle Scholar
  112. 112.
    Ponticos M, Lu QL, Morgan JE et al (1998) Dual regulation of the AMP-activated protein kinase provides a novel mechanism for the control of creatine kinase in skeletal muscle. EMBO J 17:1688–1699.  https://doi.org/10.1093/emboj/17.6.1688 CrossRefPubMedPubMedCentralGoogle Scholar
  113. 113.
    Hardie DG (2007) AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 8:774–785.  https://doi.org/10.1038/nrm2249 CrossRefPubMedGoogle Scholar
  114. 114.
    Suzuki A, Okamoto S, Lee S et al (2007) Leptin stimulates fatty acid oxidation and peroxisome proliferator-activated receptor alpha gene expression in mouse C2C12 myoblasts by changing the subcellular localization of the alpha2 form of AMP-activated protein kinase. Mol Cell Biol 27:4317–4327.  https://doi.org/10.1128/MCB.02222-06 CrossRefPubMedPubMedCentralGoogle Scholar
  115. 115.
    Andersson U, Filipsson K, Abbott CR et al (2004) AMP-activated protein kinase plays a role in the control of food intake. J Biol Chem 279:12005–12008.  https://doi.org/10.1074/jbc.C300557200 CrossRefPubMedGoogle Scholar
  116. 116.
    Yamauchi T, Kamon J, Minokoshi Y et al (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8:1288–1295.  https://doi.org/10.1038/nm788 CrossRefPubMedGoogle Scholar
  117. 117.
    Minokoshi Y, Alquier T, Furukawa N et al (2004) AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 428:569–574.  https://doi.org/10.1038/nature02440 CrossRefPubMedGoogle Scholar
  118. 118.
    Fryer LGD, Parbu-Patel A, Carling D (2002) The Anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J Biol Chem 277:25226–25232.  https://doi.org/10.1074/jbc.M202489200 CrossRefPubMedGoogle Scholar
  119. 119.
    Celenza JL, Carlson M (1986) A yeast gene that is essential for release from glucose repression encodes a protein kinase. Science 233:1175–1180CrossRefGoogle Scholar
  120. 120.
    Woods A, Munday MR, Scott J et al (1994) Yeast SNF1 is functionally related to mammalian AMP-activated protein kinase and regulates acetyl-CoA carboxylase in vivo. J Biol Chem 269:19509–19515PubMedGoogle Scholar
  121. 121.
    Mitchelhill KI, Stapleton D, Gao G et al (1994) Mammalian AMP-activated protein kinase shares structural and functional homology with the catalytic domain of yeast Snf1 protein kinase. J Biol Chem 269:2361–2364PubMedGoogle Scholar
  122. 122.
    Halford NG, Hey S, Jhurreea D et al (2004) Highly conserved protein kinases involved in the regulation of carbon and amino acid metabolism. J Exp Bot 55:35–42.  https://doi.org/10.1093/jxb/erh019 CrossRefPubMedGoogle Scholar
  123. 123.
    Jiang R, Carlson M (1997) The Snf1 protein kinase and its activating subunit, Snf4, interact with distinct domains of the Sip1/Sip2/Gal83 component in the kinase complex. Mol Cell Biol 17:2099–2106CrossRefGoogle Scholar
  124. 124.
    Nayak V, Zhao K, Wyce A et al (2006) Structure and dimerization of the kinase domain from yeast Snf1, a member of the Snf1/AMPK protein family. Struct Lond Engl 1993 14:477–485.  https://doi.org/10.1016/j.str.2005.12.008 CrossRefGoogle Scholar
  125. 125.
    Vincent O, Townley R, Kuchin S, Carlson M (2001) Subcellular localization of the Snf1 kinase is regulated by specific beta subunits and a novel glucose signaling mechanism. Genes Dev 15:1104–1114.  https://doi.org/10.1101/gad.879301 CrossRefPubMedPubMedCentralGoogle Scholar
  126. 126.
    Hong S-P, Leiper FC, Woods A et al (2003) Activation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases. Proc Natl Acad Sci USA 100:8839–8843.  https://doi.org/10.1073/pnas.1533136100 CrossRefPubMedGoogle Scholar
  127. 127.
    Nath N, McCartney RR, Schmidt MC (2003) Yeast Pak1 kinase associates with and activates Snf1. Mol Cell Biol 23:3909–3917CrossRefGoogle Scholar
  128. 128.
    Sutherland CM, Hawley SA, McCartney RR et al (2003) Elm1p is one of three upstream kinases for the Saccharomyces cerevisiae SNF1 complex. Curr Biol CB 13:1299–1305CrossRefGoogle Scholar
  129. 129.
    Shaw RJ, Kosmatka M, Bardeesy N et al (2004) The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci USA 101:3329–3335.  https://doi.org/10.1073/pnas.0308061100 CrossRefPubMedGoogle Scholar
  130. 130.
    Woods A, Dickerson K, Heath R et al (2005) Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab 2:21–33.  https://doi.org/10.1016/j.cmet.2005.06.005 CrossRefPubMedGoogle Scholar
  131. 131.
    Hong S-P, Momcilovic M, Carlson M (2005) Function of mammalian LKB1 and Ca2+/calmodulin-dependent protein kinase kinase alpha as Snf1-activating kinases in yeast. J Biol Chem 280:21804–21809.  https://doi.org/10.1074/jbc.M501887200 CrossRefPubMedGoogle Scholar
  132. 132.
    Momcilovic M, Hong S-P, Carlson M (2006) Mammalian TAK1 activates Snf1 protein kinase in yeast and phosphorylates AMP-activated protein kinase in vitro. J Biol Chem 281:25336–25343.  https://doi.org/10.1074/jbc.M604399200 CrossRefPubMedGoogle Scholar
  133. 133.
    Fujii N, Jessen N, Goodyear LJ (2006) AMP-activated protein kinase and the regulation of glucose transport. Am J Physiol Endocrinol Metab 291:E867–E877.  https://doi.org/10.1152/ajpendo.00207.2006 CrossRefPubMedGoogle Scholar
  134. 134.
    Suzuki A, Kusakai G, Kishimoto A et al (2004) IGF-1 phosphorylates AMPK-alpha subunit in ATM-dependent and LKB1-independent manner. Biochem Biophys Res Commun 324:986–992.  https://doi.org/10.1016/j.bbrc.2004.09.145 CrossRefPubMedGoogle Scholar
  135. 135.
    Li J, Miller EJ, Ninomiya-Tsuji J et al (2005) AMP-activated protein kinase activates p38 mitogen-activated protein kinase by increasing recruitment of p38 MAPK to TAB1 in the ischemic heart. Circ Res 97:872–879.  https://doi.org/10.1161/01.RES.0000187458.77026.10 CrossRefPubMedGoogle Scholar
  136. 136.
    Scarlatti F, Granata R, Meijer AJ, Codogno P (2009) Does autophagy have a license to kill mammalian cells? Cell Death Differ 16:12–20.  https://doi.org/10.1038/cdd.2008.101 CrossRefPubMedGoogle Scholar
  137. 137.
    Denton D, Nicolson S, Kumar S (2012) Cell death by autophagy: facts and apparent artefacts. Cell Death Differ 19:87–95.  https://doi.org/10.1038/cdd.2011.146 CrossRefPubMedGoogle Scholar
  138. 138.
    Herrero-Martín G, Høyer-Hansen M, García-García C et al (2009) TAK1 activates AMPK-dependent cytoprotective autophagy in TRAIL-treated epithelial cells. EMBO J 28:677–685.  https://doi.org/10.1038/emboj.2009.8 CrossRefPubMedPubMedCentralGoogle Scholar
  139. 139.
    Kim J, Kundu M, Viollet B, Guan K-L (2011) AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 13:132–141.  https://doi.org/10.1038/ncb2152 CrossRefPubMedPubMedCentralGoogle Scholar
  140. 140.
    Inoki K, Zhu T, Guan K-L (2003) TSC2 mediates cellular energy response to control cell growth and survival. Cell 115:577–590CrossRefGoogle Scholar
  141. 141.
    Gwinn DM, Shackelford DB, Egan DF et al (2008) AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 30:214–226.  https://doi.org/10.1016/j.molcel.2008.03.003 CrossRefPubMedPubMedCentralGoogle Scholar
  142. 142.
    Shin JH, Min S-H, Kim S-J et al (2013) TAK1 regulates autophagic cell death by suppressing the phosphorylation of p70 S6 kinase 1. Sci Rep 3:1561.  https://doi.org/10.1038/srep01561 CrossRefPubMedPubMedCentralGoogle Scholar
  143. 143.
    Scott RC, Schuldiner O, Neufeld TP (2004) Role and regulation of starvation-induced autophagy in the Drosophila fat body. Dev Cell 7:167–178.  https://doi.org/10.1016/j.devcel.2004.07.009 CrossRefPubMedGoogle Scholar
  144. 144.
    Daido S, Yamamoto A, Fujiwara K et al (2005) Inhibition of the DNA-dependent protein kinase catalytic subunit radiosensitizes malignant glioma cells by inducing autophagy. Cancer Res 65:4368–4375.  https://doi.org/10.1158/0008-5472.CAN-04-4202 CrossRefPubMedGoogle Scholar
  145. 145.
    Armour SM, Baur JA, Hsieh SN et al (2009) Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy. Aging 1:515–528.  https://doi.org/10.18632/aging.100056 CrossRefPubMedPubMedCentralGoogle Scholar
  146. 146.
    Hu H, Chai Y, Wang L et al (2009) Pentagalloylglucose induces autophagy and caspase-independent programmed deaths in human PC-3 and mouse TRAMP-C2 prostate cancer cells. Mol Cancer Ther 8:2833–2843.  https://doi.org/10.1158/1535-7163.MCT-09-0288 CrossRefPubMedPubMedCentralGoogle Scholar
  147. 147.
    Foster KG, Fingar DC (2010) Mammalian target of rapamycin (mTOR): conducting the cellular signaling symphony. J Biol Chem 285:14071–14077.  https://doi.org/10.1074/jbc.R109.094003 CrossRefPubMedPubMedCentralGoogle Scholar
  148. 148.
    Zoncu R, Efeyan A, Sabatini DM (2011) mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 12:21–35.  https://doi.org/10.1038/nrm3025 CrossRefPubMedGoogle Scholar
  149. 149.
    Alessi DR, Pearce LR, García-Martínez JM (2009) New insights into mTOR signaling: mTORC2 and beyond. Sci Signal 2:pe27.  https://doi.org/10.1126/scisignal.267pe27 CrossRefPubMedGoogle Scholar
  150. 150.
    Wullschleger S, Loewith R, Hall MN (2006) TOR signaling in growth and metabolism. Cell 124:471–484.  https://doi.org/10.1016/j.cell.2006.01.016 CrossRefPubMedGoogle Scholar
  151. 151.
    Kim D-H, Sarbassov DD, Ali SM et al (2003) GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR. Mol Cell 11:895–904CrossRefGoogle Scholar
  152. 152.
    Kim D-H, Sarbassov DD, Ali SM et al (2002) mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110:163–175CrossRefGoogle Scholar
  153. 153.
    Hara K, Maruki Y, Long X et al (2002) Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 110:177–189CrossRefGoogle Scholar
  154. 154.
    Sabatini DM (2006) mTOR and cancer: insights into a complex relationship. Nat Rev Cancer 6:729–734.  https://doi.org/10.1038/nrc1974 CrossRefPubMedGoogle Scholar
  155. 155.
    Hosokawa N, Hara T, Kaizuka T et al (2009) Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell 20:1981–1991.  https://doi.org/10.1091/mbc.e08-12-1248 CrossRefPubMedPubMedCentralGoogle Scholar
  156. 156.
    Sarbassov DD, Ali SM, Kim D-H et al (2004) Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol CB 14:1296–1302.  https://doi.org/10.1016/j.cub.2004.06.054 CrossRefPubMedGoogle Scholar
  157. 157.
    Pearce LR, Huang X, Boudeau J et al (2007) Identification of Protor as a novel Rictor-binding component of mTOR complex-2. Biochem J 405:513–522.  https://doi.org/10.1042/BJ20070540 CrossRefPubMedPubMedCentralGoogle Scholar
  158. 158.
    Yang Q, Inoki K, Ikenoue T, Guan K-L (2006) Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity. Genes Dev 20:2820–2832.  https://doi.org/10.1101/gad.1461206 CrossRefPubMedPubMedCentralGoogle Scholar
  159. 159.
    Sancak Y, Thoreen CC, Peterson TR et al (2007) PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. Mol Cell 25:903–915.  https://doi.org/10.1016/j.molcel.2007.03.003 CrossRefPubMedGoogle Scholar
  160. 160.
    Khanna N, Fang Y, Yoon M-S, Chen J (2013) XPLN is an endogenous inhibitor of mTORC2. Proc Natl Acad Sci USA 110:15979–15984.  https://doi.org/10.1073/pnas.1310434110 CrossRefPubMedGoogle Scholar
  161. 161.
    Bai X, Ma D, Liu A et al (2007) Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38. Science 318:977–980.  https://doi.org/10.1126/science.1147379 CrossRefPubMedGoogle Scholar
  162. 162.
    Peterson TR, Laplante M, Thoreen CC et al (2009) DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell 137:873–886.  https://doi.org/10.1016/j.cell.2009.03.046 CrossRefPubMedPubMedCentralGoogle Scholar
  163. 163.
    Nojima H, Tokunaga C, Eguchi S et al (2003) The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. J Biol Chem 278:15461–15464.  https://doi.org/10.1074/jbc.C200665200 CrossRefPubMedGoogle Scholar
  164. 164.
    Schalm SS, Blenis J (2002) Identification of a conserved motif required for mTOR signaling. Curr Biol CB 12:632–639CrossRefGoogle Scholar
  165. 165.
    Schalm SS, Fingar DC, Sabatini DM, Blenis J (2003) TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function. Curr Biol CB 13:797–806CrossRefGoogle Scholar
  166. 166.
    Choi KM, McMahon LP, Lawrence JC (2003) Two motifs in the translational repressor PHAS-I required for efficient phosphorylation by mammalian target of rapamycin and for recognition by raptor. J Biol Chem 278:19667–19673.  https://doi.org/10.1074/jbc.M301142200 CrossRefPubMedGoogle Scholar
  167. 167.
    Weng QP, Kozlowski M, Belham C et al (1998) Regulation of the p70 S6 kinase by phosphorylation in vivo. Analysis using site-specific anti-phosphopeptide antibodies. J Biol Chem 273:16621–16629CrossRefGoogle Scholar
  168. 168.
    Wang L, Rhodes CJ, Lawrence JC (2006) Activation of mammalian target of rapamycin (mTOR) by insulin is associated with stimulation of 4EBP1 binding to dimeric mTOR complex 1. J Biol Chem 281:24293–24303.  https://doi.org/10.1074/jbc.M603566200 CrossRefPubMedGoogle Scholar
  169. 169.
    Fonseca BD, Smith EM, Lee VH-Y et al (2007) PRAS40 is a target for mammalian target of rapamycin complex 1 and is required for signaling downstream of this complex. J Biol Chem 282:24514–24524.  https://doi.org/10.1074/jbc.M704406200 CrossRefPubMedGoogle Scholar
  170. 170.
    Oshiro N, Takahashi R, Yoshino K et al (2007) The proline-rich Akt substrate of 40 kDa (PRAS40) is a physiological substrate of mammalian target of rapamycin complex 1. J Biol Chem 282:20329–20339.  https://doi.org/10.1074/jbc.M702636200 CrossRefPubMedPubMedCentralGoogle Scholar
  171. 171.
    Burnett PE, Barrow RK, Cohen NA et al (1998) RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1. Proc Natl Acad Sci USA 95:1432–1437CrossRefGoogle Scholar
  172. 172.
    Chung J, Kuo CJ, Crabtree GR, Blenis J (1992) Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases. Cell 69:1227–1236CrossRefGoogle Scholar
  173. 173.
    Kuo CJ, Chung J, Fiorentino DF et al (1992) Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase. Nature 358:70–73.  https://doi.org/10.1038/358070a0 CrossRefPubMedGoogle Scholar
  174. 174.
    Price DJ, Grove JR, Calvo V et al (1992) Rapamycin-induced inhibition of the 70-kilodalton S6 protein kinase. Science 257:973–977CrossRefGoogle Scholar
  175. 175.
    Ali SM, Sabatini DM (2005) Structure of S6 kinase 1 determines whether raptor-mTOR or rictor-mTOR phosphorylates its hydrophobic motif site. J Biol Chem 280:19445–19448.  https://doi.org/10.1074/jbc.C500125200 CrossRefPubMedGoogle Scholar
  176. 176.
    Ruvinsky I, Meyuhas O (2006) Ribosomal protein S6 phosphorylation: from protein synthesis to cell size. Trends Biochem Sci 31:342–348.  https://doi.org/10.1016/j.tibs.2006.04.003 CrossRefPubMedGoogle Scholar
  177. 177.
    Kozma SC, Thomas G (2002) Regulation of cell size in growth, development and human disease: PI3K, PKB and S6K. BioEssays. News Rev Mol Cell Dev Biol 24:65–71.  https://doi.org/10.1002/bies.10031 CrossRefGoogle Scholar
  178. 178.
    Jung CH, Ro S-H, Cao J et al (2010) mTOR regulation of autophagy. FEBS Lett 584:1287–1295.  https://doi.org/10.1016/j.febslet.2010.01.017 CrossRefPubMedPubMedCentralGoogle Scholar
  179. 179.
    Meijer AJ, Codogno P (2004) Regulation and role of autophagy in mammalian cells. Int J Biochem Cell Biol 36:2445–2462.  https://doi.org/10.1016/j.biocel.2004.02.002 CrossRefPubMedGoogle Scholar
  180. 180.
    Blommaart EF, Luiken JJ, Blommaart PJ et al (1995) Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes. J Biol Chem 270:2320–2326CrossRefGoogle Scholar
  181. 181.
    Iwamaru A, Kondo Y, Iwado E et al (2007) Silencing mammalian target of rapamycin signaling by small interfering RNA enhances rapamycin-induced autophagy in malignant glioma cells. Oncogene 26:1840–1851.  https://doi.org/10.1038/sj.onc.1209992 CrossRefPubMedGoogle Scholar
  182. 182.
    Kim SY, Baik K-H, Baek K-H et al (2014) S6K1 negatively regulates TAK1 activity in the toll-like receptor signaling pathway. Mol Cell Biol 34:510–521.  https://doi.org/10.1128/MCB.01225-13 CrossRefPubMedPubMedCentralGoogle Scholar
  183. 183.
    Lu G, Kang YJ, Han J et al (2006) TAB-1 modulates intracellular localization of p38 MAP kinase and downstream signaling. J Biol Chem 281:6087–6095.  https://doi.org/10.1074/jbc.M507610200 CrossRefPubMedGoogle Scholar
  184. 184.
    Hayden MS, Ghosh S (2008) Shared principles in NF-kappaB signaling. Cell 132:344–362.  https://doi.org/10.1016/j.cell.2008.01.020 CrossRefGoogle Scholar
  185. 185.
    Sakurai H (2012) Targeting of TAK1 in inflammatory disorders and cancer. Trends Pharmacol Sci 33:522–530.  https://doi.org/10.1016/j.tips.2012.06.007 CrossRefPubMedGoogle Scholar
  186. 186.
    Mihaly SR, Ninomiya-Tsuji J, Morioka S (2014) TAK1 control of cell death. Cell Death Differ 21:1667–1676.  https://doi.org/10.1038/cdd.2014.123 CrossRefPubMedPubMedCentralGoogle Scholar
  187. 187.
    Xia Y, Shen S, Verma IM (2014) NF-κB, an active player in human cancers. Cancer Immunol Res 2:823–830.  https://doi.org/10.1158/2326-6066.CIR-14-0112 CrossRefPubMedPubMedCentralGoogle Scholar
  188. 188.
    Kimura N, Matsuo R, Shibuya H et al (2000) BMP2-induced apoptosis is mediated by activation of the TAK1-p38 kinase pathway that is negatively regulated by Smad6. J Biol Chem 275:17647–17652.  https://doi.org/10.1074/jbc.M908622199 CrossRefPubMedGoogle Scholar
  189. 189.
    Li P, Furusawa Y, Wei Z-L et al (2013) TAK1 promotes cell survival by TNFAIP3 and IL-8 dependent and NF-κB independent pathway in HeLa cells exposed to heat stress. Int J Hyperth Off J Eur Soc Hyperthermic Oncol North Am Hyperth Group 29:688–695.  https://doi.org/10.3109/02656736.2013.828104 CrossRefGoogle Scholar
  190. 190.
    Fan Y, Cheng J, Vasudevan SA et al (2013) TAK1 inhibitor 5Z-7-oxozeaenol sensitizes neuroblastoma to chemotherapy. Apoptosis Int J Program Cell Death 18:1224–1234.  https://doi.org/10.1007/s10495-013-0864-0 CrossRefGoogle Scholar
  191. 191.
    Ashkenazi A, Salvesen G (2014) Regulated cell death: signaling and mechanisms. Annu Rev Cell Dev Biol 30:337–356.  https://doi.org/10.1146/annurev-cellbio-100913-013226 CrossRefPubMedGoogle Scholar
  192. 192.
    Cho YS, Challa S, Moquin D et al (2009) Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 137:1112–1123.  https://doi.org/10.1016/j.cell.2009.05.037 CrossRefPubMedPubMedCentralGoogle Scholar
  193. 193.
    Tait SWG, Oberst A, Quarato G et al (2013) Widespread mitochondrial depletion via mitophagy does not compromise necroptosis. Cell Rep 5:878–885.  https://doi.org/10.1016/j.celrep.2013.10.034 CrossRefPubMedPubMedCentralGoogle Scholar
  194. 194.
    He S, Wang L, Miao L et al (2009) Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell 137:1100–1111.  https://doi.org/10.1016/j.cell.2009.05.021 CrossRefPubMedGoogle Scholar
  195. 195.
    Zhang D-W, Shao J, Lin J et al (2009) RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 325:332–336.  https://doi.org/10.1126/science.1172308 CrossRefGoogle Scholar
  196. 196.
    Guo X, Yin H, Chen Y et al (2016) TAK1 regulates caspase 8 activation and necroptotic signaling via multiple cell death checkpoints. Cell Death Dis 7:e2381.  https://doi.org/10.1038/cddis.2016.294 CrossRefPubMedPubMedCentralGoogle Scholar
  197. 197.
    Arslan S, Scheidereit C (2011) The prevalence of TNFα-induced necrosis over apoptosis is determined by TAK1-RIP1 interplay. PLoS ONE 6:e26069.  https://doi.org/10.1371/journal.pone.0026069 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Sabreena Aashaq
    • 1
  • Asiya Batool
    • 1
  • Khurshid I. Andrabi
    • 1
  1. 1.Department of BiotechnologyUniversity of KashmirSrinagarIndia

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