Calcineurin binds and dephosphorylates NFAT

Stable Identifier
Reaction [omitted]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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

J Biol Chem 1996
11030334 Concerted dephosphorylation of the transcription factor NFAT1 induces a conformational switch that regulates transcriptional activity

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

Mol Cell 2000
12975316 Transcriptional regulation by calcium, calcineurin, and NFAT

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

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

Uesugi, M, Park, S, 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

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

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

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

Proc Natl Acad Sci U S A 1996
Catalyst Activity

calmodulin-dependent protein phosphatase activity of Calcineurin:Calmodulin (CaN:CaM) [cytosol]

Orthologous Events
Cite Us!