Mjm. Diaz-guerra et al., Negative regulation by protein tyrosine phosphatase of IFN-gamma-dependentexpression of inducible nitric oxide synthase, J IMMUNOL, 162(11), 1999, pp. 6776-6783
Treatment of cultured peritoneal macrophages with IFN-gamma resulted in tyr
osine phosphorylation of I kappa B alpha and I kappa B beta, NF-kappa B act
ivation, and expression of inducible NO synthase (iNOS). Since tyrosine pho
sphorylation of I kappa B alpha is sufficient to activate NF-kappa B in Jur
kat cells, macrophages were treated with the protein tyrosine phosphatase i
nhibitor peroxovanadate (POV), which elicited an intense tyrosine phosphory
lation 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 B beta, 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 th
at POV potentiates the cooperation between IFN-gamma-activated transcriptio
n factors and NF-kappa B. These results indicate that tyrosine phosphorylat
ion of I kappa B is not sufficient to activate NF-kappa B in macrophages an
d propose a negative role for protein tyrosine phosphatase in the expressio
n of iNOS in response to IFN-gamma.