Serine 133-Phosphorylated CREB Induces Transcription via a Cooperative Mechanism That May Confer Specificity to Neurotrophin Signals

Azad Bonni, David D. Ginty, Henryk Dudek, Michael E. Greenberg

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)168-183
Number of pages16
JournalMolecular and Cellular Neuroscience
Volume6
Issue number2
DOIs
StatePublished - Apr 1995
Externally publishedYes

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ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Molecular Biology
  • Cell Biology
  • Developmental Neuroscience

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