title: Protein S-nitrosylation: a physiological signal for neuronal nitric oxide.
abstract: Nitric oxide (NO) has been linked to numerous physiological and pathophysiological events that are not readily explained by the well established effects of NO on soluble guanylyl cyclase. Exogenous NO S-nitrosylates cysteine residues in proteins, but whether this is an important function of endogenous NO is unclear. Here, using a new proteomic approach, we identify a population of proteins that are endogenously S-nitrosylated, and demonstrate the loss of this modification in mice harbouring a genomic deletion of neuronal NO synthase (nNOS). Targets of NO include metabolic, structural and signalling proteins that may be effectors for neuronally generated NO. These findings establish protein S-nitrosylation as a physiological signalling mechanism for nNOS.
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Jaffrey
authors.forename: H
authors.initials: H
authors.lastname: Erdjument-Bromage
authors.forename: C D
authors.initials: CD
authors.lastname: Ferris
authors.forename: P
authors.initials: P
authors.lastname: Tempst
authors.forename: S H
authors.initials: SH
authors.lastname: Snyder
mesh_terms: D000818:Animals; D019921:Biotinylation; D002531:Cerebellum / Q000737:chemistry; D011905:Genes, ras; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism; D006834:Hydrazines / Q000378:metabolism; D015151:Immunoblotting; D013058:Mass Spectrometry; D008623:Mercaptoethanol; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D009589:Nitrogen Oxides; D009603:Nitroso Compounds / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D051381:Rats; D026422:S-Nitrosoglutathione; D026403:S-Nitrosothiols
chemical_list: D006834:Hydrazines; D009419:Nerve Tissue Proteins; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D009603:Nitroso Compounds; D011506:Proteins; D020543:Proteome; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D008623:Mercaptoethanol; C032635:S-nitrosomercaptoethanol; C024942:S-nitrosopenicillamine; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; C496322:Nos1 protein, rat; D005978:Glutathione