Fig. 1.

The calcineurin-NFAT pathway. The hormone (H) binds to a Gq transmembrane protein-coupled receptor and activates the phospholipase C (PLC). The phosphatidylinositol-4,5-bisphosphate (PIP2) will be split into two lipids, one of them is a hydrosoluble- phosphoinositol triphosphate (PI3) and the other is a liposoluble- diacylglycerol (DAG). The PI3 pulls off the calcium from the endoplasmic reticulum. Calcium is an important ion to activate calmodulin, the B site of calcineurin. Only in the presence of calcium, calcineurin is active and could dephosphorylate its substrate - nuclear factor of T active cells (NFAT). Dephosphorylated NFAT is active and goes to DNA chromatin where it starts the cytokines transcription. Calcineurin activity is negative regulated by RCAN1 (the regulator of calcineurin) and immunosuppressants. NFAT is inactivated by several kinases -CK1, GSK3, DYRK. Inhibition of calcineurin-NFAT pathway will decrease T-cell cytokines production and limit the interleukins release