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Mol Cell Biol. 2000 Jan;20(2):702-12.

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

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1
Howard Hughes Medical Institute, Program in Molecular Medicine, Department of Biochemistry, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.

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.

PMID:
10611249
PMCID:
PMC85175
[Indexed for MEDLINE]
Free PMC Article

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