CREB and the CRTC co-activators: sensors for hormonal and metabolic signals

Nat Rev Mol Cell Biol. 2011 Mar;12(3):141-51. doi: 10.1038/nrm3072.


The cyclic AMP-responsive element-binding protein (CREB) is phosphorylated in response to a wide variety of signals, yet target gene transcription is only increased in a subset of cases. Recent studies indicate that CREB functions in concert with a family of latent cytoplasmic co-activators called cAMP-regulated transcriptional co-activators (CRTCs), which are activated through dephosphorylation. A dual requirement for CREB phosphorylation and CRTC dephosphorylation is likely to explain how these activator-co-activator cognates discriminate between different stimuli. Following their activation, CREB and CRTCs mediate the effects of fasting and feeding signals on the expression of metabolic programmes in insulin-sensitive tissues.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Cyclic AMP / metabolism
  • Cyclic AMP Response Element-Binding Protein / chemistry
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Glucagon / metabolism
  • Gluconeogenesis
  • Humans
  • Hyperglycemia / metabolism
  • Hypothalamus / metabolism
  • Insulin / metabolism
  • Islets of Langerhans / metabolism
  • Liver / metabolism
  • Longevity / physiology
  • Models, Biological
  • Muscle, Skeletal / metabolism
  • Phosphorylation
  • Signal Transduction
  • Trans-Activators / chemistry
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*


  • Cyclic AMP Response Element-Binding Protein
  • Insulin
  • Trans-Activators
  • Glucagon
  • Cyclic AMP