Calcineurin: Roles of the Ca²⁺/calmodulindependent protein phosphatase in diverse eukaryotes

Abstract

Calcineurin, also known as PP2B and PPP3, is a phospho-serine/threonine specific protein phosphatase that is active only after binding Ca ²⁺ and Ca ²⁺/calmodulin in response to physiological Ca ²⁺ signals. It is expressed to varying degrees in all tissues and highly conserved among most eukaryotes. Calcineurin has received much attention over the last twelve years since the discovery that the widely used immunosuppressive drugs Cyclosporin A and FK506 specifically bind and inhibit calcineurin after recruiting the cellular chaperones cyclophilin A and FKBP-12. Calcineurin is therefore unique among protein phosphatases both in its dramatic responsiveness to a second messenger and in the clinical utility of its inhibitors in a growing number of therapeutic situations. Calcineurin is widely conserved in nature and recently determined to be a major virulence factor in many pathogenic fungi. This review focuses on the progress towards understanding the broader roles of calcineurin in diverse eukaryotic species, which may offer useful insights into calcineurin function in humans.