Function and regulation of serine/threonine phosphatases in the healthy and diseased heart

J Mol Cell Cardiol. 2013 Nov;64:90-8. doi: 10.1016/j.yjmcc.2013.09.006. Epub 2013 Sep 16.

Abstract

Protein phosphorylation is a major control mechanism of a wide range of physiological processes and plays an important role in cardiac pathophysiology. Serine/threonine protein phosphatases control the dephosphorylation of a variety of cardiac proteins, thereby fine-tuning cardiac electrophysiology and function. Specificity of protein phosphatases type-1 and type-2A is achieved by multiprotein complexes that target the catalytic subunits to specific subcellular domains. Here, we describe the composition, regulation and target substrates of serine/threonine phosphatases in the heart. In addition, we provide an overview of pharmacological tools and genetic models to study the role of cardiac phosphatases. Finally, we review the role of protein phosphatases in the diseased heart, particularly in ventricular arrhythmias and atrial fibrillation and discuss their role as potential therapeutic targets.

Keywords: A-kinase-anchoring protein; AF; AKAP; AP; Atrial fibrillation; CKIP-1; Ca(2+)/calmodulin-dependent protein kinase type-II; CaMKII; Dephosphorylation; HF; Heart failure; I(Ca,L); I(K,ACh); I(K1); I(Kr); I(Ks); I(Kur); I(Na); I(NaK); L-type Ca(2+)-current; NCX1; Na(+)-current; Na(+)–Ca(2+) exchanger; Na(+)–K(+)-ATPase current; OA; PDE4D3; PKA; PKC; PLB; PP1; PP2A; Protein phosphatases; RyR2; SERCA2a; SR; TnI; acetylcholine-dependent inward-rectifier K(+)-current; action potential; atrial fibrillation; basal inward-rectifier K(+)-current; cMyBP-C; cardiac myosin-binding protein-C; casein kinase-2 interacting protein-1; heart failure; okadaic acid; phosphodiesterase-4D3; phospholamban; protein kinase-A; protein kinase-C; protein phosphatase type-1; protein phosphatase type-2A; rapid delayed-rectifier K(+)-current; ryanodine receptor type-2; sarcoplasmic reticulum; sarcoplasmic reticulum Ca(2+)-ATPase; slow delayed-rectifier K(+)-current; troponin-I; ultra-rapid delayed-rectifier K(+)-current; β-AR; β-adrenoceptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arrhythmias, Cardiac / drug therapy
  • Arrhythmias, Cardiac / genetics
  • Arrhythmias, Cardiac / metabolism
  • Arrhythmias, Cardiac / physiopathology
  • Enzyme Activation
  • Gene Expression Regulation
  • Heart / physiology*
  • Heart Diseases / drug therapy
  • Heart Diseases / genetics
  • Heart Diseases / metabolism*
  • Heart Diseases / physiopathology*
  • Humans
  • Myocardial Contraction / physiology
  • Phosphoprotein Phosphatases / antagonists & inhibitors
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphorylation

Substances

  • Phosphoprotein Phosphatases