title: CaMKII in the cardiovascular system: sensing redox states.
abstract: The multifunctional Ca(2+)- and calmodulin-dependent protein kinase II (CaMKII) is now recognized to play a central role in pathological events in the cardiovascular system. CaMKII has diverse downstream targets that promote vascular disease, heart failure, and arrhythmias, so improved understanding of CaMKII signaling has the potential to lead to new therapies for cardiovascular disease. CaMKII is a multimeric serine-threonine kinase that is initially activated by binding calcified calmodulin (Ca(2+)/CaM). Under conditions of sustained exposure to elevated Ca(2+)/CaM, CaMKII transitions into a Ca(2+)/CaM-autonomous enzyme by two distinct but parallel processes. Autophosphorylation of threonine-287 in the CaMKII regulatory domain "traps" CaMKII into an open configuration even after Ca(2+)/CaM unbinding. More recently, our group identified a pair of methionines (281/282) in the CaMKII regulatory domain that undergo a partially reversible oxidation which, like autophosphorylation, prevents CaMKII from inactivating after Ca(2+)/CaM unbinding. Here we review roles of CaMKII in cardiovascular disease with an eye to understanding how CaMKII may act as a transduction signal to connect pro-oxidant conditions into specific downstream pathological effects that are relevant to rare and common forms of cardiovascular disease.
authors: Department of Pharmacology, University of California at Davis, Davis, California 95616, USA. drjerickson@ucdavis.edu
authors: Jeffrey R
authors: JR
authors: Erickson
authors: B Julie
authors: BJ
authors: He
authors: Isabella M
authors: IM
authors: Grumbach
authors: Mark E
authors: ME
authors: Anderson
mesh_terms: D001808:Blood Vessels / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000209:etiology; D002319:Cardiovascular System / Q000201:enzymology*; D004789:Enzyme Activation / Q000502:physiology; D006333:Heart Failure / Q000503:physiopathology; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000201:enzymology; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014018:Tissue Distribution
chemical_list: D017382:Reactive Oxygen Species; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2