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Gene Review

CRTC2  -  CREB regulated transcription coactivator 2

Homo sapiens

Synonyms: CREB-regulated transcription coactivator 2, TORC-2, TORC2, Transducer of CREB protein 2, Transducer of regulated cAMP response element-binding protein 2
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Disease relevance of CRTC2

  • In contrast to the mild effects of removing HM site phosphorylation at normal levels of PI3K activity, loss of TORC2 activity strongly inhibited hyperplasia caused by elevated pathway activity, as in mutants of the tumor suppressor PTEN [1].

High impact information on CRTC2

  • TOR is part of two distinct multiprotein complexes, TOR complex 1 (TORC1), which is sensitive to rapamycin, and TORC2, which is not [2].
  • Recent biochemical studies suggested that TORC2 is the elusive PDK2 for Akt/PKB Ser473 phosphorylation in the hydrophobic motif [3].
  • Mammalian target of rapamycin (mTOR) controls cell growth and proliferation via the raptor-mTOR (TORC1) and rictor-mTOR (TORC2) protein complexes [3].
  • Our findings reveal that the SIN1-rictor-mTOR function in Akt-Ser473 phosphorylation is required for TORC2 function in cell survival but is dispensable for TORC1 function [3].
  • The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector [4].

Biological context of CRTC2

  • TORC1 and TORC2 coactivators are required for tax activation of the human T-cell leukemia virus type 1 long terminal repeats [5].
  • Here, we describe a signaling module that mediates the synergistic effects of these pathways on cellular gene expression by stimulating the dephosphorylation and nuclear entry of TORC2, a CREB coactivator [4].
  • Triggering of the calcium and cAMP second messenger pathways by glucose and gut hormones disrupts TORC2:14-3-3 complexes via complementary effects on TORC2 dephosphorylation; calcium influx increases calcineurin activity, whereas cAMP inhibits SIK2 kinase activity [4].
  • TORC2 primarily regulates cell polarity, although additional readouts of this complex are beginning to be characterized [6].
  • Under fasting conditions, the cAMP-responsive CREB coactivator TORC2 promotes glucose homeostasis by stimulating the gluconeogenic program in liver [7].

Anatomical context of CRTC2

  • Recent studies in eukaryotic cells have identified two distinct TOR complexes, TORC1 and TORC2, which phosphorylate different substrates and have distinct physiological functions [8].

Regulatory relationships of CRTC2

  • These observations clearly indicate that TORC2 activates the promoter through interaction with the BZLF1 protein as well as CREB family transcriptional factors [9].

Other interactions of CRTC2

  • This module consists of the calcium-regulated phosphatase calcineurin and the Ser/Thr kinase SIK2, both of which associate with TORC2 [4].


  1. Re-evaluating AKT regulation: role of TOR complex 2 in tissue growth. Hietakangas, V., Cohen, S.M. Genes Dev. (2007) [Pubmed]
  2. TOR signaling in growth and metabolism. Wullschleger, S., Loewith, R., Hall, M.N. Cell (2006) [Pubmed]
  3. SIN1/MIP1 Maintains rictor-mTOR Complex Integrity and Regulates Akt Phosphorylation and Substrate Specificity. Jacinto, E., Facchinetti, V., Liu, D., Soto, N., Wei, S., Jung, S.Y., Huang, Q., Qin, J., Su, B. Cell (2006) [Pubmed]
  4. The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector. Screaton, R.A., Conkright, M.D., Katoh, Y., Best, J.L., Canettieri, G., Jeffries, S., Guzman, E., Niessen, S., Yates, J.R., Takemori, H., Okamoto, M., Montminy, M. Cell (2004) [Pubmed]
  5. TORC1 and TORC2 coactivators are required for tax activation of the human T-cell leukemia virus type 1 long terminal repeats. Siu, Y.T., Chin, K.T., Siu, K.L., Yee Wai Choy, E., Jeang, K.T., Jin, D.Y. J. Virol. (2006) [Pubmed]
  6. Cell growth control: little eukaryotes make big contributions. De Virgilio, C., Loewith, R. Oncogene (2006) [Pubmed]
  7. Dual role of the coactivator TORC2 in modulating hepatic glucose output and insulin signaling. Canettieri, G., Koo, S.H., Berdeaux, R., Heredia, J., Hedrick, S., Zhang, X., Montminy, M. Cell metabolism. (2005) [Pubmed]
  8. Complexity of the TOR signaling network. Inoki, K., Guan, K.L. Trends Cell Biol. (2006) [Pubmed]
  9. TORC2, a coactivator of cAMP-response element-binding protein, promotes Epstein-Barr virus reactivation from latency through interaction with viral BZLF1 protein. Murata, T., Sato, Y., Nakayama, S., Kudoh, A., Iwahori, S., Isomura, H., Tajima, M., Hishiki, T., Ohshima, T., Hijikata, M., Shimotohno, K., Tsurumi, T. J. Biol. Chem. (2009) [Pubmed]
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