title: Rising behind NO: cGMP-dependent protein kinases.
abstract: Over the past few years, a wealth of biochemical and functional data has been gathered on mammalian cGMP-dependent protein kinases (cGKs). In mammals, three different kinases are encoded by two genes. Mutant and chimeric cGMP kinase proteins generated by molecular biology techniques have yielded important biochemical knowledge, such as the function of the N-terminal domains of cGKI and cGKII, the identity of the cGMP-binding sites of cGKI, the substrate specificity of the enzymes and structural details of the catalytic center. Genetic approaches have proved to be especially useful for the analysis of the biological function of cGKs. Recently, some of the in vivo targets and mechanisms leading to smooth muscle relaxation have been identified. In vivo targets are the myosin-binding subunit of myosin phosphatase (PP1M), a member of the protein phosphatase 1, the calcium-activated maxi K(+) channel and a new protein named IRAG that forms a complex with the inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)) receptor and cGKI. Phosphorylation of PP1M by cGKI(alpha) activates myosin phosphatase, whereas phosphorylation of IRAG by cGKI(beta) decreases Ins(1,4, 5)P(3)-induced calcium release. cGKII regulates in vivo intestinal fluid secretion by phosphorylation of the cystic fibrosis transmembrane conductance regulator (CFTR), bone growth and renal renin secretion by phosphorylation of unknown proteins.
authors.affiliation: Institut für Pharmakologie und Toxikologie, TU München, Biedersteiner Str. 29, D-80802 München, Germany. hofmann@ipt.med. tu-muenchen.de.
authors.forename: F
authors.initials: F
authors.lastname: Hofmann
authors.forename: A
authors.initials: A
authors.lastname: Ammendola
authors.forename: J
authors.initials: J
authors.lastname: Schlossmann
mesh_terms: D000818:Animals; D017869:Cyclic GMP-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*
chemical_list: D009569:Nitric Oxide; D017869:Cyclic GMP-Dependent Protein Kinases