UMMS Affiliation

Howard Hughes Medical Institute, Program in Molecular Medicine

Publication Date


Document Type



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; inhibitors; 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; inhibitors; *Tyrosine 3-Monooxygenase


Life Sciences | Medicine and Health Sciences


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.


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

Journal/Book/Conference Title

Molecular and cellular biology

Related Resources

Link to Article in PubMed

PubMed ID