Calcineurin binds and dephosphorylates NFAT1 in response to WNT/Ca2+ signaling

Stable Identifier
Reaction [transition]
Homo sapiens
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WNT/Ca2+ signaling has been shown to activate nuclear factor of activated T-cells (NFAT) in Xenopus, mouse F9 teratocarcinoma and human mammary epithelial cells (Saneyoshi et al, 2002; Ma and Wang, 2006; Demjek et al, 2006). NFAT is a transcription factor which induces genes with roles in development, cytokine production, cell-cell interaction and cancer (reviewed in Mancini and Toker, 2009). NFAT transcription activity is modulated by calcium and calcineurin concentration. In resting cells NFAT is cytoplasmic and hyperphosphorylated on fourteen conserved phosphoserine residues in three serine rich motifs termed SRR1, SP2 and SP. Upon Ca2+ induction, these serine residues are dephosphorylated by calcineurin, exposing a nuclear localization sequence and triggering translocation of the dephosphorylated NFAT-CaN complex to the nucleus. Among all the phosphorylation sites one of the sites in SRR-2 motif is not susceptible to dephosphorylation by CaN (Okamura et al, 2000; reviewed in 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

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

Mol Cell 2000
16880514 Wnt-5a/Ca2+-induced NFAT activity is counteracted by Wnt-5a/Yes-Cdc42-casein kinase 1alpha signaling in human mammary epithelial cells

Säfholm, A, Dejmek, J, Leandersson, K, Andersson, T, Kamp Nielsen, C

Mol. Cell. Biol. 2006
19851316 NFAT proteins: emerging roles in cancer progression

Mancini, M, Toker, A

Nat. Rev. Cancer 2009
12975316 Transcriptional regulation by calcium, calcineurin, and NFAT

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

Genes Dev. 2003
12015605 The Wnt/calcium pathway activates NF-AT and promotes ventral cell fate in Xenopus embryos

Kume, S, Amasaki, Y, Saneyoshi, T, Mikoshiba, K

Nature 2002
16920709 Suppression of cyclic GMP-dependent protein kinase is essential to the Wnt/cGMP/Ca2+ pathway

Wang, HY, Ma, L

J. Biol. Chem. 2006
Catalyst Activity

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

Orthologous Events
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