Serine 133-phosphorylated CREB induces transcription via a cooperative mechanism that may confer specificity to neurotrophin signals

Mol Cell Neurosci. 1995 Apr;6(2):168-83. doi: 10.1006/mcne.1995.1015.


A mechanism has been characterized by which the transcription factor CREB regulates neurotrophin-induced gene expression. Whereas CREB can mediate calcium- or cyclic AMP-induced c-fos transcription independently of other promoter-bound transcription factors, CREB mediates NGF induction of c-fos transcription via a novel mechanism that appears to require a cooperative interaction with another transcription factor, the serum response factor. A similar transcriptional mechanism may explain how neurotrophins and growth factors induce distinct subsets of delayed response genes. Neurotrophins induce the phosphorylation of CREB at a key regulatory site, Serine 133, with prolonged kinetics that are distinct from the transient kinetics of CREB phosphorylation elicited by growth factors. These results indicate that CREB is a versatile transcription factor that activates transcription via distinct mechanisms in a stimulus-specific manner. In addition, by selectively activating delayed response genes, CREB may confer specificity to neurotrophin signals that promote the survival and differentiation of neurons.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • DNA-Binding Proteins / metabolism
  • Genes, fos / drug effects
  • Genes, fos / physiology
  • Kinetics
  • Mice
  • Molecular Sequence Data
  • Nerve Growth Factors / physiology*
  • Neurons / metabolism
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • RNA, Messenger / metabolism
  • Rats
  • Serine / metabolism*
  • Serum Response Factor
  • Transcription Factors / metabolism
  • Transcription, Genetic / physiology*


  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Nerve Growth Factors
  • Nuclear Proteins
  • RNA, Messenger
  • Serum Response Factor
  • Transcription Factors
  • Serine