Interferon Induction of TAP1

The Phosphatase SHP-1 Regulates Crossover Between the IFN-/ß and the IFN- Signal-Transduction Pathways

From the Department of Pathology and the Molecular Cardiobiology Program, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Conn.

Correspondence to David R. Johnson, 454 BCMM, Yale University School of Medicine, 295 Congress Ave, New Haven, CT 06510. E-mail johnson{at}biomed.med.yale.edu

Abstract—Interferon (IFN)- and IFN-/ß induction of the transporter associated with antigen processing-1 (TAP1) promoter was compared in HeLa cells and endothelial cells (ECs). In HeLa cells, IFN- acts through Stat1/Stat1 homodimers binding to the gamma activating sequence (GAS) and IFN-/ß acts through Stat1/Stat2/p48 binding to the IFN-stimulated response element (ISRE). In ECs, however, IFN- and IFN-/ß 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 Stat1 to Stat2 proteins, and IFN-/ß also activates the same Janus kinases (JAKs) (Jak1 and tyrosine kinase (Tyk) 2 but not Jak2). However, IFN-/ß activates more Stat1 than does IFN- in ECs, whereas the reverse occurs in HeLa, and expression of the IFN-/ß receptor-associated phosphatase SHP-1 is much lower in ECs than HeLa cells. Overexpression of SHP-1 in ECs blocks IFN-/ß signaling through GAS, and expression of a dominant negative SHP-1 in HeLa cells permits IFN-/ß signaling through GAS, demonstrating a role for SHP-1 in regulating crossovers between the IFN-/ß and IFN- signaling pathways.

Key Words: endothelial cell • interferon • MHC class I • transporter associated with antigen processing (TAP) • phosphatase

This article has been cited by other articles:

				S. A. Gerber and J. S. Pober IFN-{alpha} Induces Transcription of Hypoxia-Inducible Factor-1{alpha} to Inhibit Proliferation of Human Endothelial Cells J. Immunol., July 15, 2008; 181(2): 1052 - 1062. [Abstract] [Full Text] [PDF]

				D. Ungureanu, S. Vanhatupa, J. Gronholm, J. J. Palvimo, and O. Silvennoinen SUMO-1 conjugation selectively modulates STAT1-mediated gene responses Blood, July 1, 2005; 106(1): 224 - 226. [Abstract] [Full Text] [PDF]

				L. Marques, M. Brucet, J. Lloberas, and A. Celada STAT1 Regulates Lipopolysaccharide- and TNF-{alpha}-Dependent Expression of Transporter Associated with Antigen Processing 1 and Low Molecular Mass Polypeptide 2 Genes in Macrophages by Distinct Mechanisms J. Immunol., July 15, 2004; 173(2): 1103 - 1110. [Abstract] [Full Text] [PDF]

				M. N. Sharif, I. Tassiulas, Y. Hu, I. Mecklenbrauker, A. Tarakhovsky, and L. B. Ivashkiv IFN-{alpha} Priming Results in a Gain of Proinflammatory Function by IL-10: Implications for Systemic Lupus Erythematosus Pathogenesis J. Immunol., May 15, 2004; 172(10): 6476 - 6481. [Abstract] [Full Text] [PDF]

				K. Schroder, P. J. Hertzog, T. Ravasi, and D. A. Hume Interferon-{gamma}: an overview of signals, mechanisms and functions J. Leukoc. Biol., February 1, 2004; 75(2): 163 - 189. [Abstract] [Full Text] [PDF]

				S. Mitola, M. Strasly, M. Prato, P. Ghia, and F. Bussolino IL-12 Regulates an Endothelial Cell-Lymphocyte Network: Effect on Metalloproteinase-9 Production J. Immunol., October 1, 2003; 171(7): 3725 - 3733. [Abstract] [Full Text] [PDF]

				B. Rendon-Mitchell, M. Ochani, J. Li, J. Han, H. Wang, H. Yang, S. Susarla, C. Czura, R. A. Mitchell, G. Chen, et al. IFN-{gamma} Induces High Mobility Group Box 1 Protein Release Partly Through a TNF-Dependent Mechanism J. Immunol., April 1, 2003; 170(7): 3890 - 3897. [Abstract] [Full Text] [PDF]

				D. R. Johnson Locus-Specific Constitutive and Cytokine-Induced HLA Class I Gene Expression J. Immunol., February 15, 2003; 170(4): 1894 - 1902. [Abstract] [Full Text] [PDF]

				P. T. Massa, S. L. Ropka, S. Saha, K. L. Fecenko, and K. L. Beuler Critical Role for Protein Tyrosine Phosphatase SHP-1 in Controlling Infection of Central Nervous System Glia and Demyelination by Theiler's Murine Encephalomyelitis Virus J. Virol., July 17, 2002; 76(16): 8335 - 8346. [Abstract] [Full Text] [PDF]

				K. Mahboubi and J. S. Pober Activation of Signal Transducer and Activator of Transcription 1 (STAT1) Is Not Sufficient for the Induction of STAT1-dependent Genes in Endothelial Cells. COMPARISON OF INTERFERON-gamma AND ONCOSTATIN M J. Biol. Chem., March 1, 2002; 277(10): 8012 - 8021. [Abstract] [Full Text] [PDF]

				M. Nishio, M. Tsurudome, M. Ito, M. Kawano, H. Komada, and Y. Ito High Resistance of Human Parainfluenza Type 2 Virus Protein-Expressing Cells to the Antiviral and Anti-Cell Proliferative Activities of Alpha/Beta Interferons: Cysteine-Rich V-Specific Domain Is Required for High Resistance to the Interferons J. Virol., October 1, 2001; 75(19): 9165 - 9176. [Abstract] [Full Text] [PDF]

				E. Arons, V. Kunin, C. Schechter, and R. Ehrlich Organization and Functional Analysis of the Mouse Transporter Associated with Antigen Processing 2 Promoter J. Immunol., March 15, 2001; 166(6): 3942 - 3951. [Abstract] [Full Text] [PDF]

				L. A. Cramer, S. L. Nelson, and M. J. Klemsz Synergistic Induction of the Tap-1 Gene by IFN-{gamma} and Lipopolysaccharide in Macrophages Is Regulated by STAT1 J. Immunol., September 15, 2000; 165(6): 3190 - 3197. [Abstract] [Full Text] [PDF]

				M. Weiden, N. Tanaka, Y. Qiao, B. Y. Zhao, Y. Honda, K. Nakata, A. Canova, D. E. Levy, W. N. Rom, and R. Pine Differentiation of Monocytes to Macrophages Switches the Mycobacterium tuberculosis Effect on HIV-1 Replication from Stimulation to Inhibition: Modulation of Interferon Response and CCAAT/Enhancer Binding Protein {beta} Expression J. Immunol., August 15, 2000; 165(4): 2028 - 2039. [Abstract] [Full Text] [PDF]