Roles and regulation of protein phosphatase 2A (PP2A) in the heart.
Reversible protein phosphorylation is central to a variety of cardiac processes including excitation-contraction coupling, Ca2+handling, cell metabolism, myofilament regulation, and cell-cell communication. While kinase pathways linked with elevated adrenergic signaling have been a major focus for the cardiovascular field over the past half century, new findings support the critical role of protein phosphatases in both health and disease. Protein phosphatase 2A (PP2A) is a central cardiac phosphatase that regulates diverse myocyte functions through a host of target molecules. Notably, multiple mechanisms have evolved to dynamically tune PP2A function, including modulation of the composition, phosphorylation, methylation, and localization of PP2A holoenzyme populations. Further, aberrations in this regulation of PP2A function may contribute to cardiac pathophysiology. In summary, PP2A is a critical regulatory molecule in both health and disease, with a myriad of targets in heart. Based on their unique structure, localization, and regulatory properties, PP2A subunits represent exciting therapeutic targets to modulate altered adrenergic signaling in cardiovascular disease.
Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, United States; Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH, United States.
Ellen R
ER
Lubbers
Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, United States; Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH, United States; Department of Internal Medicine, Division of Cardiovascular Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, United States. Electronic address: peter.mohler@osumc.edu.
Peter J
PJ
Mohler
D000818:Animals; D005786:Gene Expression Regulation; D006331:Heart Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D020035:Holoenzymes; D006801:Humans; D007527:Isoenzymes; D058990:Molecular Targeted Therapy; D005810:Multigene Family; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011494:Protein Kinases / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D015398:Signal Transduction
D020035:Holoenzymes; D007527:Isoenzymes; D011494:Protein Kinases; D054648:Protein Phosphatase 2
Arrhythmia; Cardiac disease; Ion channel; PP2A; Protein phosphatases