Protein S-nitrosylation: a physiological signal for neuronal nitric oxide.
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.
Jaffrey
S R
SR
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Erdjument-Bromage
H
H
Ferris
C D
CD
Tempst
P
P
Snyder
S H
SH
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
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