Metal dependent protein phosphatase PPM family in cardiac health and diseases

Protein phosphorylation and dephosphorylation is central to signal transduction in nearly every aspect of cellular function, including cardiovascular regulation and diseases. While protein kinases are often regarded as the molecular drivers in cellular signaling with high specificity and tight regulation, dephosphorylation mediated by protein phosphatases is also gaining increasing appreciation as an important part of the signal transduction network essential for the robustness, specificity and homeostasis of cell signaling. Metal dependent protein phosphatases (PPM, also known as protein phosphatases type 2C, PP2C) belong to a highly conserved family of protein phosphatases with unique biochemical and molecular features. Accumulating evidence also indicates important and specific functions of individual PPM isoform in signaling and cellular processes, including proliferation, senescence, apoptosis and metabolism. At the physiological level, abnormal PPM expression and activity have been implicated in major human diseases, including cancer, neurological and cardiovascular disorders. Finally, inhibitors for some of the PPM members have been developed as a potential therapeutic strategy for human diseases. In this review, we will focus on the background information about the biochemical and molecular features of major PPM family members, with emphasis on their demonstrated or potential roles in cardiac pathophysiology. The current challenge and potential directions for future investigations will also be highlighted.