title: Role of myosin light chain phosphatase in cardiac physiology and pathophysiology.
abstract: Maintenance of contractile performance of the heart is achieved in part by the constitutive 40% phosphorylation of myosin regulatory light chain (RLC) in sarcomeres. The importance of this extent of RLC phosphorylation for optimal cardiac performance becomes apparent when various mouse models and resultant phenotypes are compared. The absence or attenuation of RLC phosphorylation results in poor performance leading to heart failure, whereas increased RLC phosphorylation is associated with cardiac protection from stresses. Although information is limited, RLC phosphorylation appears compromised in human heart failure which is consistent with data from mouse studies. The extent of cardiac RLC phosphorylation is determined by the balanced activities of cardiac myosin light chain kinases and phosphatases, the regulatory mechanisms of which are now emerging. This review thusly focuses on kinases that may participate in phosphorylating RLC to make the substrate for cardiac myosin light chain phosphatases, in addition to providing perspectives on the family of myosin light chain phosphatases and involved signaling mechanisms. Because biochemical and physiological information about cardiac myosin light chain phosphatase is sparse, such studies represent an emerging area of investigation in health and disease.
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: audreyn.chang@utsouthwestern.edu.
authors.forename: Audrey N
authors.initials: AN
authors.lastname: Chang
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Kamm
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: James T
authors.initials: JT
authors.lastname: Stull
mesh_terms: D000818:Animals; D006321:Heart / Q000502:physiology*; D006331:Heart Diseases / Q000209:etiology* / Q000378:metabolism*; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D018994:Myosin Light Chains / Q000737:chemistry / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase / Q000737:chemistry / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D012518:Sarcomeres / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D018994:Myosin Light Chains; D009219:Myosin-Light-Chain Kinase; D010744:Phosphoric Monoester Hydrolases; D043263:Myosin-Light-Chain Phosphatase
keywords: Cardiac contraction; Myosin; Myosin light chain kinase; Myosin light chain phosphatase; Regulatory light chain; Sarcomere