title: Cardiac myosin is a substrate for zipper-interacting protein kinase (ZIPK).
abstract: Zipper-interacting protein kinase (ZIPK) is a member of the death-associated protein kinase family associated with apoptosis in nonmuscle cells where it phosphorylates myosin regulatory light chain (RLC) to promote membrane blebbing. ZIPK mRNA and protein are abundant in heart tissue and isolated ventricular neonatal rat cardiac myocytes. An unbiased substrate search performed with purified ZIPK on heart homogenates led to the discovery of a prominent 20-kDa protein substrate identified as RLC of ventricular myosin. Biochemical analyses showed ZIPK phosphorylated cardiac RLC at Ser-15 with a V(max) value 2-fold greater than the value for smooth/nonmuscle RLC; cardiac RLC is a favorable biochemical substrate. Knockdown of ZIPK in cardiac myocytes by small interfering RNA significantly decreased the extent of RLC Ser-15 phosphorylation. Thus, ZIPK may act as a cardiac RLC kinase and thereby affect contractility.
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Audrey N
authors.initials: AN
authors.lastname: Chang
authors.forename: Guohua
authors.initials: G
authors.lastname: Chen
authors.forename: Robert D
authors.initials: RD
authors.lastname: Gerard
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Kamm
authors.forename: James T
authors.initials: JT
authors.lastname: Stull
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D064550:Death-Associated Protein Kinases; D006352:Heart Ventricles / Q000378:metabolism*; D051379:Mice; D032386:Myoblasts, Cardiac / Q000378:metabolism*; D009200:Myocardial Contraction / Q000502:physiology*; D018994:Myosin Light Chains / Q000378:metabolism*; D009928:Organ Specificity / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology; D051381:Rats
chemical_list: D051017:Apoptosis Regulatory Proteins; D018994:Myosin Light Chains; C579100:Dapk3 protein, mouse; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases