title: Regulation of sGC via hsp90, Cellular Heme, sGC Agonists, and NO: New Pathways and Clinical Perspectives.
abstract: Soluble guanylate cyclase (sGC) is an intracellular enzyme that plays a primary role in sensing nitric oxide (NO) and transducing its multiple signaling effects in mammals. Recent Advances: The chaperone heat shock protein 90 (hsp90) associates with signaling proteins in cells, including sGC, where it helps to drive heme insertion into the sGC-β1 subunit. This allows sGC-β1 to associate with a partner sGC-α1 subunit and mature into an NO-responsive active form.
  
  
  
  In this article, we review evidence to date regarding the mechanisms that modulate sGC activity by a pathway where binding of hsp90 or sGC agonist to heme-free sGC dictates the assembly and fate of an active sGC heterodimer, both by NO and heme-dependent or heme-independent pathways.
  
  
  
  We discuss some therapeutic implications of the NO-sGC-hsp90 nexus and its potential as a marker of inflammatory disease. Antioxid. Redox Signal. 26, 182-190.
authors.affiliation: Department of Pathobiology, Lerner Research Institute , Cleveland Clinic, Cleveland, Ohio.
authors.forename: Arnab
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Department of Pathobiology, Lerner Research Institute , Cleveland Clinic, Cleveland, Ohio.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Stuehr
mesh_terms: D015415:Biomarkers; D003600:Cytosol; D004198:Disease Susceptibility; D056890:Eukaryota / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006418:Heme / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D015398:Signal Transduction; D000071756:Soluble Guanylyl Cyclase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018841:HSP90 Heat-Shock Proteins; D009569:Nitric Oxide; D006418:Heme; D019001:Nitric Oxide Synthase; D000071756:Soluble Guanylyl Cyclase
keywords: S-nitrosation; cGMP; desensitization; nitrosylation; signal transduction