In vivo inactivation of phosphotyrosine protein phosphatases by nitric oxide.
The effect of NO on phosphotyrosine protein phosphatases (PTPases) has been investigated in vivo. NO production is induced in interferon-gamma and lipopolysaccharide stimulated RAW-264.7 macrophages as indicated by the increase of NO2- in the medium. Our results demonstrate an inhibition of p-nitrophenylphosphatase activity as a consequence of macrophages activation. Under the described experimental conditions, most of the hydrolysis of p-nitrophenylphosphate can be ascribed to the action of cellular PTPases. The presence of NG-mono-methyl-L-arginine, a specific inhibitor of NO synthase decreases the inactivation rate of both membrane-bound and soluble PTPases. This evidence further confirms the ability of NO to inactivate PTPases and suggests a possible role of NO in the regulation of cellular processes involving this class of phosphatases.
Caselli
A
A
Dipartimento di Scienze Biochimiche, Universita' di Firenze, Italia.
Chiarugi
P
P
Camici
G
G
Manao
G
G
Ramponi
G
G
D000818:Animals; D002461:Cell Line, Transformed; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016898:Interferon-alpha / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000201:enzymology / Q000276:immunology; D051379:Mice; D009569:Nitric Oxide / Q000494:pharmacology*; D009596:Nitrophenols / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D016898:Interferon-alpha; D008070:Lipopolysaccharides; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D009569:Nitric Oxide; C008644:nitrophenylphosphate; D017027:Protein Tyrosine Phosphatases