A growth factor-induced kinase phosphorylates the serum response factor at a site that regulates its DNA-binding activity

Victor M. Rivera, Cindy K. Miranti, Ravi P. Misra, David D. Ginty, Rey Huei Chen, John Blenis, Michael E. Greenberg

Research output: Contribution to journalArticle

Abstract

A signaling pathway by which growth factors may induce transcription of the c-fos proto-oncogene has been characterized. Growth factor stimulation of quiescent fibroblasts activates a protein kinase cascade that leads to the rapid and transient phosphorylation of the serum response factor (SRF), a regulator of c-fos transcription. The in vivo kinetics of SRF phosphorylation and dephosphorylation parallel the activation and subsequent repression of c-fos transcription, suggesting that this phosphorylation event plays a critical role in the control of c-fos expression. The ribosomal S6 kinase pp90rsk, a growth factor-inducible kinase, phosphorylates SRF in vitro at serine 103, the site that becomes newly phosphorylated upon growth factor stimulation in vivo. Phosphorylation of serine 103 significantly enhances the affinity and rate with which SRF associates with its binding site, the serum response element, within the c-fos promoter. These results suggest a model in which the growth factor-induced phosphorylation of SRF at serine 103 contributes to the activation of c-fos transcription by facilitating the formation of an active transcription complex at the serum response element.

Original languageEnglish (US)
Pages (from-to)6260-6273
Number of pages14
JournalMolecular and Cellular Biology
Volume13
Issue number10
StatePublished - Oct 1993
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

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    Rivera, V. M., Miranti, C. K., Misra, R. P., Ginty, D. D., Chen, R. H., Blenis, J., & Greenberg, M. E. (1993). A growth factor-induced kinase phosphorylates the serum response factor at a site that regulates its DNA-binding activity. Molecular and Cellular Biology, 13(10), 6260-6273.