Nerve growth factor activates a Ras-dependent protein kinase that stimulates c-fos transcription via phosphorylation of CREB

Cell. 1994 Jun 3;77(5):713-25. doi: 10.1016/0092-8674(94)90055-8.


A mechanism by which the nerve growth factor (NGF) signal is transduced to the nucleus to induce gene expression has been characterized. An NGF-inducible, Ras-dependent protein kinase has been identified that catalyzes the phosphorylation of the cyclic AMP response element-binding protein (CREB) at Ser-133. Phosphorylation of Ser-133 stimulates the ability of CREB to activate transcription in NGF-treated cells. These findings suggest that CREB has a more widespread function than previously believed and functions in the nucleus as a general mediator of growth factor responses.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Enzyme Activation / drug effects
  • GTPase-Activating Proteins
  • Genes, fos* / drug effects
  • Mice
  • Nerve Growth Factors / pharmacology*
  • Phosphorylation
  • Protein Kinases / metabolism*
  • Proteins / metabolism
  • Rats
  • Signal Transduction / drug effects
  • Transcription, Genetic / drug effects
  • ras GTPase-Activating Proteins


  • Cyclic AMP Response Element-Binding Protein
  • GTPase-Activating Proteins
  • Nerve Growth Factors
  • Proteins
  • ras GTPase-Activating Proteins
  • Protein Kinases