L-type voltage-sensitive calcium channel activation stimulates gene expression by a serum response factor-dependent pathway

J Biol Chem. 1994 Oct 14;269(41):25483-93.

Abstract

A mechanism by which calcium-induced signals are transduced to the nucleus to activate transcription of the c-fos proto-oncogene has been characterized. The serum response element (SRE), a region of the c-fos gene which controls growth factor-induced transcription, is now shown to mediate c-fos transcription in response to activation of L-type voltage-sensitive calcium channels. Calcium-dependent transcriptional activation through the SRE is mediated by the serum response factor (SRF). Membrane depolarization induces phosphorylation of SRF at Ser-103, an event shown to enhance the ability of SRF to bind the SRE. Ca(2+)-induced SRF phosphorylation occurs via a pathway that may involve Ca2+/calmodulin-dependent kinases.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Calcium / metabolism
  • Calcium Channels / physiology*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 4
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cell Membrane / physiology
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Gene Expression Regulation*
  • Membrane Potentials
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • PC12 Cells
  • Phosphorylation
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins c-fos / genetics*
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Serum Response Factor
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic

Substances

  • Calcium Channels
  • DNA-Binding Proteins
  • Fungal Proteins
  • GAL4 protein, S cerevisiae
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-fos
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Serum Response Factor
  • Transcription Factors
  • Calcium-Calmodulin-Dependent Protein Kinase Type 4
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Camk4 protein, rat
  • Calcium