Integration of calcium and cyclic AMP signaling pathways by 14-3-3

Chi Wing Chow, Roger J. Davis

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

Calcium-stimulated nuclear factor of activated T cells (NFAT) transcription activity at the interleukin-2 promoter is negatively regulated by cyclic AMP (cAMP). This effect of cAMP is mediated, in part, by protein kinase A phosphorylation of NFAT. The mechanism of regulation involves the creation of a phosphorylation-dependent binding site for 14-3-3. Decreased NFAT phosphorylation caused by the calcium-stimulated phosphatase calcineurin, or mutation of the PKA phosphorylation sites, disrupted 14-3-3 binding and increased NFAT transcription activity. In contrast, NFAT phosphorylation caused by cAMP increased 14-3-3 binding and reduced NFAT transcription activity. The regulated interaction between NFAT and 14-3-3 provides a mechanism for the integration of calcium and cAMP signaling pathways.

Original languageEnglish (US)
Pages (from-to)702-712
Number of pages11
JournalMolecular and cellular biology
Volume20
Issue number2
DOIs
StatePublished - Jan 2000

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Integration of calcium and cyclic AMP signaling pathways by 14-3-3'. Together they form a unique fingerprint.

  • Cite this