title: Calmodulin is a subunit of nitric oxide synthase from macrophages.
abstract: A central issue in nitric oxide (NO) research is to understand how NO can act in some settings as a servoregulator and in others as a cytotoxin. To answer this, we have sought a molecular basis for the differential regulation of the two known types of NO synthase (NOS). Constitutive NOS's in endothelium and neurons are activated by agonist-induced elevation of Ca2+ and resultant binding of calmodulin (CaM). In contrast, NOS in macrophages does not require added Ca2+ or CaM, but is regulated instead by transcription. We show here that macrophage NOS contains, as a tightly bound subunit, a molecule with the immunologic reactivity, high performance liquid chromatography retention time, tryptic map, partial amino acid sequence, and exact molecular mass of CaM. In contrast to most CaM-dependent enzymes, macrophage NOS binds CaM tightly without a requirement for elevated Ca2+. This may explain why NOS that is independent of Ca2+ and elevated CaM appears to be activated simply by being synthesized.
authors.affiliation: Beatrice and Samuel A. Seaver Laboratory, Department of Medicine, Cornell University Medical College, New York, New York 10021.
authors.forename: H J
authors.initials: HJ
authors.lastname: Cho
authors.forename: Q W
authors.initials: QW
authors.lastname: Xie
authors.forename: J
authors.initials: J
authors.lastname: Calaycay
authors.forename: R A
authors.initials: RA
authors.lastname: Mumford
authors.forename: K M
authors.initials: KM
authors.lastname: Swiderek
authors.forename: T D
authors.initials: TD
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Nathan
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000737:chemistry*; D000818:Animals; D002147:Calmodulin / Q000032:analysis*; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D008264:Macrophages / Q000201:enzymology*; D019001:Nitric Oxide Synthase
chemical_list: D002147:Calmodulin; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases