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

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.
Mesh Terms:
14-3-3 Proteins, Amino Acid Sequence, Animals, Binding Sites, Bucladesine, Calcineurin, Calcium, Calcium Signaling, Cell Line, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, DNA-Binding Proteins, Gene Expression Regulation, Humans, Interleukin-2, Ionomycin, Molecular Sequence Data, Mutation, NFATC Transcription Factors, Nuclear Localization Signals, Nuclear Proteins, Phosphorylation, Phosphoserine, Proteins, Recombinant Fusion Proteins, Signal Transduction, Transcription Factors, Tyrosine 3-Monooxygenase
Mol. Cell. Biol.
Date: Jan. 01, 2000
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