Interferon induction of TAP1: the phosphatase SHP-1 regulates crossover between the IFN-alpha/beta and the IFN-gamma signal-transduction pathways.
Interferon (IFN)-gamma and IFN-alpha/beta induction of the transporter associated with antigen processing-1 (TAP1) promoter was compared in HeLa cells and endothelial cells (ECs). In HeLa cells, IFN-gamma acts through Stat1alpha/Stat1alpha homodimers binding to the gamma activating sequence (GAS) and IFN-alpha/beta acts through Stat1/Stat2/p48 binding to the IFN-stimulated response element (ISRE). In ECs, however, IFN-gamma and IFN-alpha/beta act through both the GAS and ISRE. The basis of the IFN signaling crossover in ECs was investigated. HeLa and ECs contain similar ratios of Stat1alpha to Stat2 proteins, and IFN-alpha/beta also activates the same Janus kinases (JAKs) (Jak1 and tyrosine kinase (Tyk) 2 but not Jak2). However, IFN-alpha/beta activates more Stat1alpha than does IFN-gamma in ECs, whereas the reverse occurs in HeLa, and expression of the IFN-alpha/beta receptor-associated phosphatase SHP-1 is much lower in ECs than HeLa cells. Overexpression of SHP-1 in ECs blocks IFN-alpha/beta signaling through GAS, and expression of a dominan negative SHP-1 in HeLa cells permits IFN-alpha/ss signaling through GAS, demonstrating a role for SHP-1 in regulating crossovers between the IFN-alpha/beta and IFN-gamma signaling pathways.
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Department of Pathology and the Molecular Cardiobiology Program, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
Pober
J S
JS
Johnson
D R
DR
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000502:physiology; D019281:Dimerization; D004727:Endothelium / Q000166:cytology / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D008285:Major Histocompatibility Complex / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000502:physiology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D018909:src Homology Domains / Q000502:physiology
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D004268:DNA-Binding Proteins; C494227:IRF9 protein, human; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; C073119:TAP1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016899:Interferon-beta; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases