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Título

Negative regulation by protein tyrosine phosphatase of IFN-γ-dependent expression of inducible nitric oxide synthase

AutorDíaz-Guerra, María José; Castrillo, Antonio ; Martín-Sanz, Paloma ; Boscá, Lisardo
Fecha de publicación1-jun-1999
EditorAmerican Association of Immunologists
CitaciónJournal of Immunology 162(11): 6776-6783 (1999)
ResumenTreatment of cultured peritoneal macrophages with IFN-{gamma} resulted in tyrosine phosphorylation of I{kappa}B{alpha} and I{kappa}Bß, NF-{kappa}B activation, and expression of inducible NO synthase (iNOS). Since tyrosine phosphorylation of I{kappa}B{alpha} is sufficient to activate NF-{kappa}B in Jurkat cells, macrophages were treated with the protein tyrosine phosphatase inhibitor peroxovanadate (POV), which elicited an intense tyrosine phosphorylation of both I{kappa}B. However, this phosphorylation failed to activate NF-{kappa}B. Treatment with POV of macrophages stimulated with IFN-{gamma} or LPS potentiated the degradation of I{kappa}B{alpha} and I{kappa}Bß, the activation of NF-{kappa}B, and the expression of iNOS. Analysis of the iNOS gene promoter activity corresponding to the 5'-flanking region indicated that POV potentiates the cooperation between IFN-{gamma}-activated transcription factors and NF-{kappa}B. These results indicate that tyrosine phosphorylation of I{kappa}B is not sufficient to activate NF-{kappa}B in macrophages and propose a negative role for protein tyrosine phosphatase in the expression of iNOS in response to IFN-{gamma}.
Descripción9 pages, 6 figures.
Versión del editorhttp://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=10352298
URIhttp://hdl.handle.net/10261/24375
ISSN0022-1767
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