Differential tyrosine phosphorylation of the IFNAR chain of the type I interferon receptor and of an associated surface protein in response to IFN-alpha and IFN-beta - PubMed (original) (raw)
Differential tyrosine phosphorylation of the IFNAR chain of the type I interferon receptor and of an associated surface protein in response to IFN-alpha and IFN-beta
C Abramovich et al. EMBO J. 1994.
Abstract
The human interferon alpha-receptor (IFNAR gene product) is a transmembranal protein of 557 amino acids with an intracytoplasmic domain of 100 amino acids containing four tyrosines. Antibodies to a C-terminal peptide (residues 521-536) were developed which efficiently immunoprecipitate the 105 kDa IFNAR protein from detergent extracts of human cells. We show that the IFNAR protein becomes tyrosine phosphorylated within 5 min after treatment of human myeloma U266 cells with IFN-alpha 2, IFN-alpha 8 or IFN-beta. The IFNAR chain interacts with both IFN-alpha 2 and IFN-beta, as demonstrated by cross-linking. Among elements involved in signal transduction by type I IFNs, the tyrosine kinase Tyk2 but not Jak1, and the ISGF3 transcription factor subunit Stat2 (p113) but not Stat1 (p91), are found associated with the IFNAR protein. After IFN-beta treatment for 5 min, a tyrosine-phosphorylated protein of approximately 95 kDa (beta-PTyr) is found bound to IFNAR, but can be dissociated by denaturation. The beta-PTyr protein is present on the cell surface, like IFNAR, as shown by extracellular biotin tagging. The ratio of beta-PTyr to IFNAR tyrosine phosphorylation is much higher with IFN-beta than with IFN-alpha 2 or 8. Both are IFN dependent and abrogated by a monoclonal antibody which blocks IFNAR action. The beta-PTyr component may represent an important difference in the action of IFN-beta as compared with IFN-alpha in their shared receptor system.
Similar articles
- The neutralization of type I IFN biologic actions by anti-IFNAR-2 monoclonal antibodies is not entirely due to inhibition of Jak-Stat tyrosine phosphorylation.
Novick D, Nabioullin RR, Ragsdale W, McKenna S, Weiser W, Garone L, Burkins C, Kim SH, Rubinstein M, Tepper MA, Arulanandam AR. Novick D, et al. J Interferon Cytokine Res. 2000 Nov;20(11):971-82. doi: 10.1089/10799900050198417. J Interferon Cytokine Res. 2000. PMID: 11096454 - Catalytically active TYK2 is essential for interferon-beta-mediated phosphorylation of STAT3 and interferon-alpha receptor-1 (IFNAR-1) but not for activation of phosphoinositol 3-kinase.
Rani MR, Leaman DW, Han Y, Leung S, Croze E, Fish EN, Wolfman A, Ransohoff RM. Rani MR, et al. J Biol Chem. 1999 Nov 5;274(45):32507-11. doi: 10.1074/jbc.274.45.32507. J Biol Chem. 1999. PMID: 10542297 - The proximal tyrosines of the cytoplasmic domain of the beta chain of the type I interferon receptor are essential for signal transducer and activator of transcription (Stat) 2 activation. Evidence that two Stat2 sites are required to reach a threshold of interferon alpha-induced Stat2 tyrosine phosphorylation that allows normal formation of interferon-stimulated gene factor 3.
Nadeau OW, Domanski P, Usacheva A, Uddin S, Platanias LC, Pitha P, Raz R, Levy D, Majchrzak B, Fish E, Colamonici OR. Nadeau OW, et al. J Biol Chem. 1999 Feb 12;274(7):4045-52. doi: 10.1074/jbc.274.7.4045. J Biol Chem. 1999. PMID: 9933596 - How cancer cells make and respond to interferon-I.
Cheon H, Wang Y, Wightman SM, Jackson MW, Stark GR. Cheon H, et al. Trends Cancer. 2023 Jan;9(1):83-92. doi: 10.1016/j.trecan.2022.09.003. Epub 2022 Oct 8. Trends Cancer. 2023. PMID: 36216730 Free PMC article. Review. - Modeling Arboviral Infection in Mice Lacking the Interferon Alpha/Beta Receptor.
Marín-Lopez A, Calvo-Pinilla E, Moreno S, Utrilla-Trigo S, Nogales A, Brun A, Fikrig E, Ortego J. Marín-Lopez A, et al. Viruses. 2019 Jan 8;11(1):35. doi: 10.3390/v11010035. Viruses. 2019. PMID: 30625992 Free PMC article. Review.
Cited by
- Molecular characterization of an alpha interferon receptor 1 subunit (IFNaR1) domain required for TYK2 binding and signal transduction.
Yan H, Krishnan K, Lim JT, Contillo LG, Krolewski JJ. Yan H, et al. Mol Cell Biol. 1996 May;16(5):2074-82. doi: 10.1128/MCB.16.5.2074. Mol Cell Biol. 1996. PMID: 8628273 Free PMC article. - IFN-zeta/ limitin: a member of type I IFN with mild lympho-myelosuppression.
Oritani K, Kanakura Y. Oritani K, et al. J Cell Mol Med. 2005 Apr-Jun;9(2):244-54. doi: 10.1111/j.1582-4934.2005.tb00353.x. J Cell Mol Med. 2005. PMID: 15963247 Free PMC article. Review. - Multifarious determinants of cytokine receptor signaling specificity.
Moraga I, Spangler J, Mendoza JL, Garcia KC. Moraga I, et al. Adv Immunol. 2014;121:1-39. doi: 10.1016/B978-0-12-800100-4.00001-5. Adv Immunol. 2014. PMID: 24388212 Free PMC article. Review. - Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 kDa STAT2 protein.
Yan H, Krishnan K, Greenlund AC, Gupta S, Lim JT, Schreiber RD, Schindler CW, Krolewski JJ. Yan H, et al. EMBO J. 1996 Mar 1;15(5):1064-74. EMBO J. 1996. PMID: 8605876 Free PMC article. - A protein-arginine methyltransferase binds to the intracytoplasmic domain of the IFNAR1 chain in the type I interferon receptor.
Abramovich C, Yakobson B, Chebath J, Revel M. Abramovich C, et al. EMBO J. 1997 Jan 15;16(2):260-6. doi: 10.1093/emboj/16.2.260. EMBO J. 1997. PMID: 9029147 Free PMC article.
References
- Pharmacol Ther. 1991 Nov;52(2):227-33 - PubMed
- J Immunol. 1992 Apr 1;148(7):2126-32 - PubMed
- J Natl Cancer Inst. 1992 Aug 5;84(15):1185-90 - PubMed
- Cell. 1992 Jul 24;70(2):313-22 - PubMed
- Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7840-3 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous