The Role of Protein Tyrosine Phosphatase SHP-1 in the Regulation of IFN-γ Signaling in Neural Cells

The role for protein tyrosine phosphatase SHP-1 in controlling signal transduction by IFN-γ in astrocytes was studied. IFN-γ induced the γ-activated factor (GAF) within 30 min and GAF subsequently declined by 8 h after treatment. However, treatment with IFN-γ in the presence of protein tyrosine phosphatase inhibitor vanadate blocked the decrease in GAF activity. The increased stability of GAF in vanadate-treated cultures was similarly observed in astrocytes of motheaten mice, which specifically lack the protein tyrosine phosphatase SHP-1. Prolongation of GAF activity coincided with increased expression of the IFN-inducible transcription factor, IFN-regulatory factor-1 (IRF-1). Increased IRF-1 was coincident with increased expression of MHC class I molecules in astrocytes in accordance with the activity of IRF-1 in the promoter region. These data implicate an important role for protein tyrosine phosphatases, including SHP-1, in the regulation of IFN-γ-signaling and IFN-γ-inducible genes in neural cells.