Meta-Biol

• Pathways

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).