Phosphorylation of the human interferon-γ (IFNγ) receptor was studied in three cell lines of distinct lineages using radiophosphate labeling techniques. Receptors from unstimulated Colo-205 displayed a low level of constitutive phosphorylation which was enhanced 5.3-fold following exposure of the cells to either purified recombinant human IFNγ or phorbol myristate acetate. Enhanced receptor phosphorylation was specific, dose- and time-dependent, reversible, and affected only serine and threonine residues. Increased phosphorylation was observed only when cells were treated with human IFNγ or phorbol myristate acetate and not with murine IFNγ, human IFNα, human tumor necrosis factor-α, or epidermal growth factor. The biologic relevance of IFNγ receptor phosphorylation was suggested by three additional observations; 1) there was a close correlation between the extent of receptor phosphorylation and the magnitude of the cellular response induced, 2) TNFα concomitantly enhanced both IFNγ-dependent HLA-DR expression and IFNγ-dependent receptor phosphorylation on Colo-205, and 3) phosphorylation of functionally inactive recombinant murine IFNγ receptors expressed on transfected human 293 or Colo-205 cells was not induced by murine IFNγ but was induced by the homologous human ligand. These results suggest that phosphorylation of the IFNγ receptor is an important step in development of IFNγ-dependent cellular responses and indicates that phosphorylation requires a functionally active receptor.
|Number of pages||8|
|Journal||Journal of Biological Chemistry|
|State||Published - 1990|