Calcium, Calcineurin and the Control of Transcription
Gerald R. Crabtree, The American Society for Biochemistry and Molecular Biology, Inc.
Calcineurin (PP2B), a serine threonine kinase controlled by cellular calcium, was originally identified by Klee and colleagues in extracts of mammalian brain. Within the past few years this phosphatase has been implicated in a wide variety of biological responses including lymphocyte activation, neuronal and muscle development, axonal pathfinding and morphogenesis of vertebrate heart valves. Progress in this area has been greatly accelerated by the drugs cyclosporin A and FK506, which use a unique mechanism of action to achieve near genome-specific nanamolar inhibition of calcineurin. This minireview will focus on the role of calcineurin in regulating transcription during development, primarily through its dephosphorylation of downstream targets, such as the cytoplasmic subunits of the NF-AT transcription complex.