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

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

Stable Identifier

R-HSA-4551451

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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

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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