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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.

作者:Jordi, Heijman;Matthias, Dewenter;Ali, El-Armouche;Dobromir, Dobrev

来源:Journal of molecular and cellular cardiology 2013 年 64卷

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作者:
Jordi, Heijman;Matthias, Dewenter;Ali, El-Armouche;Dobromir, Dobrev
来源:
Journal of molecular and cellular cardiology 2013 年 64卷
标签:
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
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.