(A) In IFN-γ, GM-CSF, and IL-6 stimulated cells, GSK3 inhibition suppressed both STAT3 and STAT5 activity, but only minimally affected STAT1 and STAT6 activity. (B) GSK3-β inhibition differentially affects early and late STAT1 activation in IFN-γ-treated cells. Inhibition of GSK3 had no effect on early STAT1 activity (<1hr) but diminished late STAT1 phosphorylation by increasing SHP-2 activity. The ability of GSK3 inhibition to reduce STAT1 activity resulted in reduced levels of iNOS, TNF, and RANTES by IFN-γ-stimulated macrophages.