title: An inducible nitric-oxide synthase (NOS)-associated protein inhibits NOS dimerization and activity.
abstract: A variety of transcriptional and post-transcriptional mechanisms regulate the expression of the inducible nitric-oxide synthase (iNOS, or NOS2). Although neurons and endothelial cells express proteins that interact with and inhibit neuronal NOS and endothelial NOS, macrophage proteins that inhibit NOS2 have not been identified. We show that murine macrophages express a 110-kDa protein that interacts with NOS2, which we call NOS-associated protein-110 kDa (NAP110). NAP110 directly interacts with the amino terminus of NOS2, and inhibits NOS catalytic activity by preventing formation of NOS2 homodimers. Expression of NAP110 may be a mechanism by which macrophages expressing NOS2 protect themselves from cytotoxic levels of nitric oxide.
authors.affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Ratovitski
authors.forename: C
authors.initials: C
authors.lastname: Bao
authors.forename: R A
authors.initials: RA
authors.lastname: Quick
authors.forename: A
authors.initials: A
authors.lastname: McMillan
authors.forename: C
authors.initials: C
authors.lastname: Kozlovsky
authors.forename: C J
authors.initials: CJ
authors.lastname: Lowenstein
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D019281:Dimerization; D051379:Mice; D008969:Molecular Sequence Data; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D020033:Protein Isoforms / Q000378:metabolism; D013379:Substrate Specificity; D014415:Tunicamycin / Q000494:pharmacology; D020798:Two-Hybrid System Techniques
chemical_list: D020033:Protein Isoforms; D014415:Tunicamycin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse