Interferon (IFN-) signals through a multimeric receptor complex consisting of two different chains: the IFN- receptor binding subunit (IFN-R, IFN-R1), and a transmembrane accessory factor (AF-1, IFN-R2) necessary for signal transduction. Using cell lines expressing different cloned components of the IFN- receptor complex, we examined the function of the receptor components in signal transduction upon IFN- treatment. A specific IFN-R2:IFN- cross-linked complex was observed in cells expressing both IFN-R1 and IFN-R2 indicating that IFN-R2 (AF-1) interacts with IFN- and is closely associated with IFN-R1. We show that the intracellular domain of IFN-R2 is necessary for signaling. Cells coexpressing IFN-R1 and truncated IFN-R2, lacking the COOH-terminal 51 amino acids (residues 286-337), or cells expressing IFN-R1 alone were unresponsive to IFN- treatment as measured by MHC class I antigen induction. Jak1, Jak2, and Stat1 were activated, and IFN-R1 was phosphorylated only in cells expressing both IFN-R1 and IFN-R2. Jak2 kinase was shown to associate with the intracellular domain of the IFN-R2.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				K. C. Tang, K. A. Trzaska, S. V. Smirnov, S. V. Kotenko, S. K. Schwander, J. J. Ellner, and P. Rameshwar Down-Regulation of MHC II in Mesenchymal Stem Cells at High IFN-{gamma} Can Be Partly Explained by Cytoplasmic Retention of CIITA J. Immunol., February 1, 2008; 180(3): 1826 - 1833. [Abstract] [Full Text] [PDF]

				S. J. Greco, S. V. Smirnov, R. G. Murthy, and P. Rameshwar Synergy between the RE-1 Silencer of Transcription and NF{kappa}B in the Repression of the Neurotransmitter Gene TAC1 in Human Mesenchymal Stem Cells J. Biol. Chem., October 12, 2007; 282(41): 30039 - 30050. [Abstract] [Full Text] [PDF]

				C. S. Garcia, R. E. Curiel, J. M. Mwatibo, S. Pestka, H. Li, and I. Espinoza-Delgado The Antineoplastic Agent Bryostatin-1 Differentially Regulates IFN-{gamma} Receptor Subunits in Monocytic Cells: Transcriptional and Posttranscriptional Control of IFN-{gamma}R2 J. Immunol., August 15, 2006; 177(4): 2707 - 2716. [Abstract] [Full Text] [PDF]

				H. Takaki, Y. Minoda, K. Koga, G. Takaesu, A. Yoshimura, and T. Kobayashi TGF-beta1 suppresses IFN-gamma-induced NO production in macrophages by suppressing STAT1 activation and accelerating iNOS protein degradation. Genes Cells, August 1, 2006; 11(8): 871 - 882. [Abstract] [Full Text] [PDF]

				G. S. Cooke, S. J. Campbell, J. Sillah, P. Gustafson, B. Bah, G. Sirugo, S. Bennett, K. P. W. J. McAdam, O. Sow, C. Lienhardt, et al. Polymorphism within the Interferon-{gamma}/Receptor Complex Is Associated with Pulmonary Tuberculosis Am. J. Respir. Crit. Care Med., August 1, 2006; 174(3): 339 - 343. [Abstract] [Full Text] [PDF]

				S. Wormald, J.-G. Zhang, D. L. Krebs, L. A. Mielke, J. Silver, W. S. Alexander, T. P. Speed, N. A. Nicola, and D. J. Hilton The Comparative Roles of Suppressor of Cytokine Signaling-1 and -3 in the Inhibition and Desensitization of Cytokine Signaling J. Biol. Chem., April 21, 2006; 281(16): 11135 - 11143. [Abstract] [Full Text] [PDF]

				A. P. Costa-Pereira, H. M. Hermanns, H. Is'harc, T. M. Williams, D. Watling, V. Arulampalam, S. J. Newman, P. C. Heinrich, and I. M. Kerr Signaling through a Mutant IFN-{gamma} Receptor J. Immunol., November 1, 2005; 175(9): 5958 - 5965. [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]

				C. D. Krause, E. Mei, J. Xie, Y. Jia, M. A. Bopp, R. M. Hochstrasser, and S. Pestka Seeing the Light: Preassembly and Ligand-Induced Changes of the Interferon {gamma} Receptor Complex in Cells Mol. Cell. Proteomics, October 1, 2002; 1(10): 805 - 815. [Abstract] [Full Text] [PDF]

				P. S. Subramaniam and H. M. Johnson Lipid Microdomains Are Required Sites for the Selective Endocytosis and Nuclear Translocation of IFN-{gamma}, Its Receptor Chain IFN-{gamma} Receptor-1, and the Phosphorylation and Nuclear Translocation of STAT1{alpha} J. Immunol., August 15, 2002; 169(4): 1959 - 1969. [Abstract] [Full Text] [PDF]

				G. Gri, C. Chiodoni, E. Gallo, A. Stoppacciaro, F. Y. Liew, and M. P. Colombo Antitumor Effect of Interleukin (IL)-12 in the Absence of Endogenous IFN-{gamma}: A Role for Intrinsic Tumor Immunogenicity and IL-15 Cancer Res., August 1, 2002; 62(15): 4390 - 4397. [Abstract] [Full Text] [PDF]

				T. D. Joseph and D. C. Look Specific Inhibition of Interferon Signal Transduction Pathways by Adenoviral Infection J. Biol. Chem., December 7, 2001; 276(50): 47136 - 47142. [Abstract] [Full Text] [PDF]

				S. V. Kotenko, L. S. Izotova, O. V. Mirochnitchenko, E. Esterova, H. Dickensheets, R. P. Donnelly, and S. Pestka Identification, Cloning, and Characterization of a Novel Soluble Receptor That Binds IL-22 and Neutralizes Its Activity J. Immunol., June 15, 2001; 166(12): 7096 - 7103. [Abstract] [Full Text] [PDF]

				P. Najarro, P. Traktman, and J. A. Lewis Vaccinia Virus Blocks Gamma Interferon Signal Transduction: Viral VH1 Phosphatase Reverses Stat1 Activation J. Virol., April 1, 2001; 75(7): 3185 - 3196. [Abstract] [Full Text]

				S. Goodbourn, L. Didcock, and R. E. Randall Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures J. Gen. Virol., October 1, 2000; 81(10): 2341 - 2364. [Full Text]

				H. Skrenta, Y. Yang, S. Pestka, and C. G. Fathman Ligand-Independent Down-Regulation of IFN-{gamma} Receptor 1 Following TCR Engagement J. Immunol., April 1, 2000; 164(7): 3506 - 3511. [Abstract] [Full Text] [PDF]

				S. V. Kotenko, S. Saccani, L. S. Izotova, O. V. Mirochnitchenko, and S. Pestka Human cytomegalovirus harbors its own unique IL-10 homolog (cmvIL-10) PNAS, February 15, 2000; 97(4): 1695 - 1700. [Abstract] [Full Text] [PDF]

				P. Subramaniam, J Larkin, M. Mujtaba, M. Walter, and H. Johnson The COOH-terminal nuclear localization sequence of interferon gamma regulates STAT1 alpha nuclear translocation at an intracellular site J. Cell Sci., January 8, 2000; 113(15): 2771 - 2781. [Abstract] [PDF]

				S. V. Kotenko, L. S. Izotova, O. V. Mirochnitchenko, C. Lee, and S. Pestka The intracellular domain of interferon-alpha receptor 2c (IFN-alpha R2c) chain is responsible for Stat activation PNAS, April 27, 1999; 96(9): 5007 - 5012. [Abstract] [Full Text] [PDF]

				M. JACKSON, S. E. M. HOWIE, R. WELLER, E. SABIN, J. A. A. HUNTER, and R. C. McKENZIE Psoriatic keratinocytes show reduced IRF-1 and STAT-1{alpha} activation in response to {gamma}-IFN FASEB J, March 1, 1999; 13(3): 495 - 502. [Abstract] [Full Text]

				B. Lu, C. Ebensperger, Z. Dembic, Y. Wang, M. Kvatyuk, T. Lu, R. L. Coffman, S. Pestka, and P. B. Rothman Targeted disruption of the interferon-gamma receptor 2 gene results in severe immune defects in mice PNAS, July 7, 1998; 95(14): 8233 - 8238. [Abstract] [Full Text] [PDF]

				M. Kanzaki and P. L. Morris Identification and Regulation of Testicular Interferon-{gamma} (IFN{gamma}) Receptor Subunits: IFN{gamma} Enhances Interferon Regulatory Factor-1 and Interleukin-1{beta} Converting Enzyme Expression Endocrinology, May 1, 1998; 139(5): 2636 - 2644. [Abstract] [Full Text] [PDF]

				D. M. Miller, B. M. Rahill, J. M. Boss, M. D. Lairmore, J. E. Durbin, J. W. Waldman, and D. D. Sedmak Human Cytomegalovirus Inhibits Major Histocompatibility Complex Class II Expression By Disruption of the Jak/Stat Pathway J. Exp. Med., March 2, 1998; 187(5): 675 - 683. [Abstract] [Full Text] [PDF]

				Y. Aragane, D. Kulms, T. A. Luger, and T. Schwarz Down-regulation of interferon gamma -activated STAT1 by UV light PNAS, October 14, 1997; 94(21): 11490 - 11495. [Abstract] [Full Text] [PDF]

				G. Muthukumaran, S. Kotenko, R. Donnelly, J. N. Ihle, and S. Pestka Chimeric Erythropoietin-Interferon gamma Receptors Reveal Differences in Functional Architecture of Intracellular Domains for Signal Transduction J. Biol. Chem., February 21, 1997; 272(8): 4993 - 4999. [Abstract] [Full Text] [PDF]

				M. J. Newport, C. M. Huxley, S. Huston, C. M. Hawrylowicz, B. A. Oostra, R. Williamson, and M. Levin A Mutation in the Interferon-{gamma} -Receptor Gene and Susceptibility to Mycobacterial Infection N. Engl. J. Med., December 26, 1996; 335(26): 1941 - 1949. [Abstract] [Full Text] [PDF]

				D. Lembo, P. Ricciardi-Castagnoli, G. Alber, L. Ozmen, S. Landolfo, H. Bluthmann, Z. Dembic, S. V. Kotenko, J. R. Cook, S. Pestka, et al. Mouse Macrophages Carrying Both Subunits of the Human Interferon-gamma (IFN-gamma ) Receptor Respond to Human IFN-gamma but Do Not Acquire Full Protection against Viral Cytopathic Effect J. Biol. Chem., December 20, 1996; 271(51): 32659 - 32666. [Abstract] [Full Text] [PDF]

				N. Patel, J. M. Herrman, J. C. Timans, and R. A. Kastelein Functional Replacement of Cytokine Receptor Extracellular Domains by Leucine Zippers J. Biol. Chem., November 29, 1996; 271(48): 30386 - 30391. [Abstract] [Full Text] [PDF]

				S. Rhee, C. Ebensperger, Z. Dembic, and S. Pestka The Structure of the Gene for the Second Chain of the Human Interferon-gamma Receptor J. Biol. Chem., November 15, 1996; 271(46): 28947 - 28952. [Abstract] [Full Text] [PDF]

				S. V. Kotenko, L. S. Izotova, B. P. Pollack, G. Muthukumaran, K. Paukku, O. Silvennoinen, J. N. Ihle, and S. Pestka Other Kinases Can Substitute for Jak2 in Signal Transduction by Interferon-gamma J. Biol. Chem., July 19, 1996; 271(29): 17174 - 17182. [Abstract] [Full Text] [PDF]

				D. H. Kaplan, A. C. Greenlund, J. W. Tanner, A. S. Shaw, and R. D. Schreiber Identification of an Interferon-[IMAGE] Receptor alpha Chain Sequence Required for JAK-1 Binding J. Biol. Chem., January 5, 1996; 271(1): 9 - 12. [Abstract] [Full Text] [PDF]

				S. V. Kotenko, L. S. Izotova, O. V. Mirochnitchenko, E. Esterova, H. Dickensheets, R. P. Donnelly, and S. Pestka Identification of the Functional Interleukin-22 (IL-22) Receptor Complex. THE IL-10R2 CHAIN (IL-10Rbeta ) IS A COMMON CHAIN OF BOTH THE IL-10 AND IL-22 (IL-10-RELATED T CELL-DERIVED INDUCIBLE FACTOR, IL-TIF) RECEPTOR COMPLEXES J. Biol. Chem., January 19, 2001; 276(4): 2725 - 2732. [Abstract] [Full Text] [PDF]

				S. Sarkar, B. P. Pollack, K.-T. Lin, S. V. Kotenko, J. R. Cook, A. Lewis, and S. Pestka hTid-1, a Human DnaJ Protein, Modulates the Interferon Signaling Pathway J. Biol. Chem., December 21, 2001; 276(52): 49034 - 49042. [Abstract] [Full Text] [PDF]

				C. D. Krause, C. A. Lunn, L. S. Izotova, O. Mirochnitchenko, S. V. Kotenko, D. J. Lundell, S. K. Narula, and S. Pestka Signaling by Covalent Heterodimers of Interferon-gamma . EVIDENCE FOR ONE-SIDED SIGNALING IN THE ACTIVE TETRAMERIC RECEPTOR COMPLEX J. Biol. Chem., July 21, 2000; 275(30): 22995 - 23004. [Abstract] [Full Text] [PDF]