Figure 7. Schematic view of the NFATc2 switch.

The NFATc2 switch can be regarded at the molecular, cellular and population levels as shown in the proposed model. First, at the molecular level, the dephosphorylation of 13 Serine residues of NFATc2 by calcineurin (CaN) leads to a conformational switch of an NFATc2 molecule from an inactive to an active conformation that exposes a nuclear localization sequence (NLS) and allows NFATc2 to enter the nucleus [24]. Second, at the cellular level, the nature of cooperativity of a minimum of 7 dephosphorylation sites (Hill coefficient n = 6) can account for a steep response curve and, consequently, a quantitative translocation of all the NFATc2 per cell by stimulation above a threshold with ionomycin. Third, at the population level, there are only cells with all-or-none NFATc2 in the nuclei.