Calcineurin binds and dephosphorylates NFAT

Stable Identifier
R-HSA-2730849
Type
Reaction [omitted]
Species
Homo sapiens
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Nuclear factor of activated T-cells (NFAT) is a transcription factor which induces genes responsible for cytokine production, for cell-cell interactions etc. NFAT transcription activity is modulated by calcium and Calcineurin concentration. In resting cells NFAT is phosphorylated and resides in the cytoplasm. Phosphorylation sites are located in NFAT's regulatory domain in three different serine rich motifs, termed SRR1, SP2 and SP. Upon stimulation, these serine residues are dephosphorylated by calcineurin, that thought to cause exposure of nuclear localization signal sequences triggering translocation of the dephosphorylated NFAT-CaN complex to the nucleus. Among all the phosphorylation sites one of the site in SRR-2 motif is not susceptable to dephosphorylation by CaN (Takeuchi et al. 2007, Hogan et al. 2003).

Literature References
PubMed ID Title Journal Year
11030334 Concerted dephosphorylation of the transcription factor NFAT1 induces a conformational switch that regulates transcriptional activity

Okamura, H, Aramburu, J, García-Rodríguez, C, Viola, JP, Raghavan, A, Tahiliani, M, Zhang, X, Qin, J, Hogan, PG, Rao, A

Mol Cell 2000
8631904 Calcineurin binds the transcription factor NFAT1 and reversibly regulates its activity

Loh, C, Shaw, KT, Carew, J, Viola, JP, Luo, C, Perrino, BA, Rao, A

J Biol Chem 1996
12975316 Transcriptional regulation by calcium, calcineurin, and NFAT

Hogan, PG, Chen, L, Nardone, J, Rao, A

Genes Dev. 2003
10860980 A second calcineurin binding site on the NFAT regulatory domain

Park, S, Uesugi, M, Verdine, GL

Proc Natl Acad Sci U S A 2000
17502104 Structure of the calcineurin-NFAT complex: defining a T cell activation switch using solution NMR and crystal coordinates

Takeuchi, K, Roehrl, MH, Sun, ZY, Wagner, G

Structure 2007
8799126 Interaction of calcineurin with a domain of the transcription factor NFAT1 that controls nuclear import

Luo, C, Shaw, KT, Raghavan, A, Aramburu, J, Garcia-Cozar, F, Perrino, BA, Hogan, PG, Rao, A

Proc Natl Acad Sci U S A 1996
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Catalyst Activity
Title
calmodulin-dependent protein phosphatase activity of Calcineurin:Calmodulin (CaN:CaM) [cytosol]
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Orthologous Events
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