Role of calcineurin biosignaling in cell secretion and the possible regulatory mechanisms.

Cyclic adenosine monophosphate (cAMP) and calcium ions (Ca) are two chemical molecules that play a central role in the stimulus-dependent secretion processes within cells. Ca acts as the basal signaling molecule responsible to initiate cell secretion. cAMP primarily acts as an intracellular second messenger in a myriad of cellular processes by activating cAMP-dependent protein kinases through association with such kinases in order to mediate post-translational phosphorylation of those protein targets. Put succinctly, both Ca and cAMP act by associating or activating other proteins to ensure successful secretion. Calcineurin is one such protein regulated by Ca; its action depends on the intracellular levels of Ca. Being a phosphatase, calcineurin dephosphorylate and other proteins, as is the case with most other phosphatases, such as protein phosphatase 2A (PP2A), PP2C, and protein phosphatase-1 (PP1), will likely be activated by phosphorylation. Via this process, calcineurin is able to affect different intracellular signaling with clinical importance, some of which has been the basis for development of different calcineurin inhibitors. In this review, the cAMP-dependent calcineurin bio-signaling, protein-protein interactions and their physiological implications as well as regulatory signaling within the context of cellular secretion are explored.