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Molecular biology of the cell
Nov, 2008;19 (11): 4750-61.

Activation of TORC1 transcriptional coactivator through MEKK1-induced phosphorylation.

Yeung-Tung Siu, Yick-Pang Ching, Dong-Yan Jin
Author Information
  1. Yeung-Tung Siu: Department of Biochemistry and Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong.
PMID: 18784253 DOI: 10.1091/mbc.e08-04-0369

Abstract

CREB is a prototypic bZIP transcription factor and a master regulator of glucose metabolism, synaptic plasticity, cell growth, apoptosis, and tumorigenesis. Transducers of regulated CREB activity (TORCs) are essential transcriptional coactivators of CREB and an important point of regulation on which various signals converge. In this study, we report on the activation of TORC1 through MEKK1-mediated phosphorylation. MEKK1 potently activated TORC1, and this activation was independent of downstream effectors MEK1/MEK2, ERK2, JNK, p38, protein kinase A, and calcineurin. MEKK1 induced phosphorylation of TORC1 both in vivo and in vitro. Expression of the catalytic domain of MEKK1 alone in cultured mammalian cells sufficiently caused phosphorylation and subsequent activation of TORC1. MEKK1 physically interacted with TORC1 and stimulated its nuclear translocation. An activation domain responsive to MEKK1 stimulation was mapped to amino acids 431-650 of TORC1. As a physiological activator of CREB, interleukin 1alpha triggered MEKK1-dependent phosphorylation of TORC1 and its consequent recruitment to the cAMP response elements in the interleukin 8 promoter. Taken together, our findings suggest a new mechanism for regulated activation of TORC1 transcriptional coactivator and CREB signaling.

References

  1. J Virol. 2006 Sep;80(18):9279-87 [PMID: 16940539]
  2. Mol Cell Endocrinol. 2007 Feb;265-266:196-204 [PMID: 17210223]
  3. Oncogene. 2007 May 14;26(22):3240-53 [PMID: 17496919]
  4. J Leukoc Biol. 2002 Nov;72(5):847-55 [PMID: 12429706]
  5. Oncogene. 2002 Jun 27;21(28):4384-91 [PMID: 12080469]
  6. Mol Cell Biol. 2008 Mar;28(5):1644-56 [PMID: 18086876]
  7. EMBO J. 2007 Jun 20;26(12):2890-903 [PMID: 17525731]
  8. Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4700-5 [PMID: 17360587]
  9. J Biol Chem. 2003 Sep 26;278(39):37439-50 [PMID: 12876282]
  10. J Biol Chem. 2007 Jun 15;282(24):17649-57 [PMID: 17452327]
  11. J Biol Chem. 1996 Oct 18;271(42):25731-4 [PMID: 8824197]
  12. Cancer Cell. 2004 Nov;6(5):447-58 [PMID: 15542429]
  13. J Biol Chem. 1990 Mar 25;265(9):5267-72 [PMID: 2156866]
  14. EMBO J. 2005 Jul 6;24(13):2391-402 [PMID: 15961999]
  15. Cell. 2004 Oct 1;119(1):61-74 [PMID: 15454081]
  16. FEBS J. 2006 Jun;273(12):2730-48 [PMID: 16817901]
  17. PLoS One. 2006 Dec 20;1:e16 [PMID: 17183642]
  18. Nat Rev Mol Cell Biol. 2001 Aug;2(8):599-609 [PMID: 11483993]
  19. J Biol Chem. 1990 Dec 5;265(34):21128-33 [PMID: 2250017]
  20. J Biol Chem. 1998 Jul 17;273(29):18623-32 [PMID: 9660836]
  21. J Biol Chem. 1992 Nov 5;267(31):22506-11 [PMID: 1331059]
  22. J Biol Chem. 2006 Jul 21;281(29):20427-39 [PMID: 16684769]
  23. Gene Ther. 2008 Feb;15(3):191-202 [PMID: 17972920]
  24. J Biol Chem. 2004 Dec 17;279(51):52978-83 [PMID: 15466468]
  25. Oncogene. 2007 May 14;26(22):3159-71 [PMID: 17496913]
  26. Nucleic Acids Res. 2005 Mar 30;33(6):1859-73 [PMID: 15800215]
  27. Science. 2008 Mar 7;319(5868):1402-5 [PMID: 18323454]
  28. J Biol Chem. 2003 Jan 17;278(3):1403-6 [PMID: 12456688]
  29. Cell Metab. 2005 Nov;2(5):331-8 [PMID: 16271533]
  30. FEBS J. 2007 Jul;274(13):3202-9 [PMID: 17565599]
  31. Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13681-6 [PMID: 11717429]
  32. J Virol. 2006 Jul;80(14):7052-9 [PMID: 16809310]
  33. J Biol Chem. 1999 Jun 18;274(25):17402-5 [PMID: 10364167]
  34. J Biol Chem. 2001 May 11;276(19):16310-7 [PMID: 11278389]
  35. Nucleic Acids Res. 1998 Jan 15;26(2):486-9 [PMID: 9421504]
  36. FEBS J. 2007 Jul;274(13):3224-32 [PMID: 17565603]
  37. Mol Cell. 2003 Aug;12(2):413-23 [PMID: 14536081]
  38. Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):7945-50 [PMID: 12048245]
  39. Mol Cell Biol. 2007 Jan;27(2):510-7 [PMID: 17101801]
  40. Nature. 2007 Sep 20;449(7160):366-9 [PMID: 17805301]
  41. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10541-6 [PMID: 9724739]
  42. J Exp Med. 2008 Oct 27;205(11):2551-60 [PMID: 18838543]
  43. Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):10161-6 [PMID: 18626018]
  44. Mol Cell. 2002 May;9(5):945-56 [PMID: 12049732]
  45. EMBO J. 2007 Jun 20;26(12):2880-9 [PMID: 17476304]
  46. Nature. 1994 Dec 22-29;372(6508):798-800 [PMID: 7997270]
  47. Nature. 2005 Oct 20;437(7062):1109-11 [PMID: 16148943]
  48. Annu Rev Biochem. 2006;75:137-63 [PMID: 16756488]
  49. Annu Rev Biochem. 1999;68:821-61 [PMID: 10872467]
  50. Cancer Res. 2005 Aug 15;65(16):7137-44 [PMID: 16103063]
  51. J Biol Chem. 1999 Apr 16;274(16):10916-22 [PMID: 10196170]
  52. Proc Natl Acad Sci U S A. 2000 May 9;97(10):5243-8 [PMID: 10805784]
  53. Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14379-84 [PMID: 16980408]
  54. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20314-9 [PMID: 18077367]
  55. Curr Biol. 2004 Dec 14;14(23):2156-61 [PMID: 15589160]
  56. Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12147-52 [PMID: 14506290]
  57. Cell Signal. 2004 Nov;16(11):1211-27 [PMID: 15337521]
  58. Retrovirology. 2004 Jul 30;1:18 [PMID: 15285791]
  59. J Biol Chem. 2007 Sep 28;282(39):28335-28343 [PMID: 17644518]
  60. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5291-5 [PMID: 8643568]
  61. Mol Cell Biol. 1998 Feb;18(2):967-77 [PMID: 9447994]
  62. FEBS Lett. 1998 Apr 10;426(1):93-6 [PMID: 9598985]
  63. Nat Cell Biol. 2006 Jul;8(7):717-24 [PMID: 16767081]
  64. Mol Cell Biol. 2000 Sep;20(17):6612-25 [PMID: 10938135]
  65. Immunology. 1989 Sep;68(1):31-6 [PMID: 2478449]
  66. Cell. 1991 Aug 23;66(4):807-15 [PMID: 1715244]
  67. Annu Rev Immunol. 2000;18:217-42 [PMID: 10837058]
  68. J Biol Chem. 1997 Oct 10;272(41):25816-23 [PMID: 9325311]
  69. Science. 2005 Dec 9;310(5754):1642-6 [PMID: 16308421]
  70. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10175-80 [PMID: 17548807]

Grants

  1. R01 TW006186/FIC NIH HHS
  2. R01 TW06186-01/FIC NIH HHS

MeSH Term

Calcineurin
Cell Nucleus
Cyclic AMP-Dependent Protein Kinases
Extracellular Signal-Regulated MAP Kinases
HeLa Cells
Humans
Interleukin-8
JNK Mitogen-Activated Protein Kinases
MAP Kinase Kinase Kinase 1
Phosphorylation
Phosphothreonine
Promoter Regions, Genetic
Protein Binding
Protein Structure, Tertiary
Protein Transport
Trans-Activators
Transcription Factors
Transcription, Genetic
p38 Mitogen-Activated Protein Kinases

Chemicals

CRTC1 protein, human
Interleukin-8
Trans-Activators
Transcription Factors
Phosphothreonine
Cyclic AMP-Dependent Protein Kinases
Extracellular Signal-Regulated MAP Kinases
JNK Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases
MAP Kinase Kinase Kinase 1
MAP3K1 protein, human
Calcineurin
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
Article has an altmetric score of 3

Word Cloud

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