The @entity563 / XXXX phosphatase inhibitor, @entity29478 , inhibits and dissociates macrophage responses to lipopolysaccharide.

@entity558 @entity29478 @entity326 @entity19 @entity635 @entity26187 @entity12421 @entity3721 @entity563 @entity1889 @entity669 @entity637 @entity15369
@entity558 -stimulated macrophages (M phi) produce inflammatory mediators that are largely responsible for the pathophysiology associated with @entity326 . M phi respond to @entity558 with rapid protein phosphorylation and dephosphorylation on @entity563 , @entity1889 , and @entity669 residues. If these events are critical for the cellular response to @entity558 , the kinases and/or phosphatases involved may be vulnerable targets for pharmacologic intervention. Recent studies demonstrated that @entity669 kinase inhibitors block @entity558 -induced @entity669 phosphorylation of MAP kinases as well as @entity637 and @entity635 production. To investigate a role for @entity563 / @entity1889 phosphatases, we evaluated the effect of @entity29478 , a potent @entity563 / @entity1889 phosphatase inhibitor, on @entity558 stimulation of @entity19 M phi. Pretreatment of M phi with @entity29478 inhibited @entity558 -induced expression of six immediate-early genes: @entity637 , @entity635 , @entity12421 , @entity15369 , @entity26187 , and @entity3721 . @entity29478 added 1.5 h after @entity558 treatment greatly reduced accumulation of @entity15369 , @entity26187 , and @entity3721 mRNA, but not @entity637 , @entity635 , and @entity12421 mRNA. @entity29478 , in the absence or presence of @entity558 , resulted in sustained @entity669 phosphorylation of the MAP kinases. These findings suggest that an "early" @entity563 / @entity1889 phosphatase activity is essential for @entity558 stimulation of M phi and that the activation of MAP kinases is not sufficient for the induction of these immediate-early genes. The requirement for a "late" phosphatase activity for expression of a subset of @entity558 -inducible genes dissociates at least two regulatory pathways in @entity558 signal transduction.
