title: CaMKII isoforms differ in their specific requirements for regulation by nitric oxide.
abstract: The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) mediates physiological and pathological functions by its Ca(2+)-independent autonomous activity. Two novel mechanisms for generating CaMKII autonomy include oxidation and S-nitrosylation, the latter requiring both Cys280 and Cys289 amino acid residues in the brain-specific isoform CaMKIIα. Even though the other CaMKII isoforms have a different amino acid in the position homologous to Cys280, we show here that nitric oxide (NO)-signaling generated autonomy also for the CaMKIIβ isoform. Furthermore, although oxidation of the Met280/281 residues is sufficient to generate autonomy for most CaMKII isoforms, oxidation-induced autonomy was also prevented by a Cys289-mutation in the CaMKIIα isoform. Thus, all CaMKII isoforms can be regulated by physiological NO-signaling, but CaMKIIα regulation by oxidation and S-nitrosylation is more stringent.
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: steve.coultrap@ucdenver.edu.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Coultrap
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Zaegel
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: ulli.bayer@ucdenver.edu.
authors.forename: K Ulrich
authors.initials: KU
authors.lastname: Bayer
mesh_terms: D000595:Amino Acid Sequence; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
chemical_list: D007527:Isoenzymes; D009569:Nitric Oxide; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: Autonomy; CaMKII; Calmodulin; Kinase regulation; Nitric oxide; Oxidation; S-nitrosylation