Reactome | Calcineurin binds and dephosphorylates NFAT

Calcineurin binds and dephosphorylates NFAT

Stable Identifier

R-HSA-2730849

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Calcineurin binds and dephosphorylates NFAT

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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
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
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
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