Tyrosine phosphorylation is an early and requisite signal induced by interferon-gamma in HL-60 cells

Interferon-gamma (IFN gamma) is a potent immunomodulatory cytokine. However, the early mechanisms which mediate the pleiotropic effects of IFN gamma on different cells are as yet poorly understood. Therefore, we tested the role of tyrosine phosphorylation in signalling induced by IFN gamma. IFN gamma was found to induce rapid tyrosine phosphorylation of several proteins in HL-60 cells. This effect was detectable by 2 min, reached a maximum by about 4-16 min and thereafter declined. Tyrosine phosphorylation was dependent on receptor occupation and was maximally stimulated by 10 ng/ml IFN gamma. Treatment of HL-60 cells with the tyrosine kinase inhibitors, genistein and herbimycin A, inhibited both IFN gamma-stimulated tyrosine phosphorylation and IFN gamma-induced Fc receptor expression. Thus, increased tyrosine phosphorylation appears to be an obligatory early and proximal signal mediating at least some of the later cellular responses induced by IFN gamma in HL-60 cells.