Calcineurin as a multifunctional regulator

Long recognized as an important regulatory mechanism in biosignal processes, modulation of the phosphorylation state of proteins has emerged as the most important mechanism for understanding signal transduction. In contrast to the multitude of protein kinases and the clear signal transduction pathways, relatively few protein phosphatases are known and their regulation is unclear. Among them, calcineurin, a calcium/calmodulin-dependent phosphatase (PP2B), is the best enzyme to unveil the phosphatase function, because it was shown to be the direct target for immunosuppressants CsA and FK506, which are powerful tools for understanding this function in diseases as well as in several tissues and organs. Although calcineurin has been found in the highest concentrations in brain, it has also been detected in many other mammalian tissues. Well characterized in T cell activation by analysing the transcription factor NFAT, the function of calcineurin, however, was less well understood in other tissues and organs. Since the mid-1990s, several novel functions of this phosphatase have been reported, revealing that it plays important roles as a multifunctional regulator under the direct regulation of calcium signaling.