The role of protein tyrosine phosphatase SHP-1 in the regulation of IFN-gamma signaling in neural cells.
The role for protein tyrosine phosphatase SHP-1 in controlling signal transduction by IFN-gamma in astrocytes was studied. IFN-gamma induced the gamma-activated factor (GAF) within 30 min and GAF subsequently declined by 8 h after treatment. However, treatment with IFN-gamma 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-gamma-signaling and IFN-gamma-inducible genes in neural cells.
Massa
P T
PT
The State University of New York, Health Science Center, Department of Neurology, Syracuse 13210, USA.
Wu
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C
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D050856:Interferon Regulatory Factor-1; D050832:Interferon-Stimulated Gene Factor 3; D007371:Interferon-gamma / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009154:Mutation; D015345:Oligonucleotide Probes / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D014638:Vanadates / Q000494:pharmacology
D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; D050856:Interferon Regulatory Factor-1; D050832:Interferon-Stimulated Gene Factor 3; D047908:Intracellular Signaling Peptides and Proteins; C494258:Irf1 protein, mouse; D015345:Oligonucleotide Probes; D010750:Phosphoproteins; D014157:Transcription Factors; C079868:gamma interferon activation factor; D014638:Vanadates; D007371:Interferon-gamma; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse