title: Different strategies for producing naturally soluble form of common cytokine receptor γ chain.
abstract: The common cytokine receptor γ chain (γc) plays an essential role in regulating lymphoid homeostasis. In fact, alteration of this gene causes severe immunodeficiency in humans and animals. Although soluble γc (sγc) was identified in the late 1990s, much remains unknown about its production. This study describes various mechanisms underlying the generation of sγc isoforms in different species. Our data demonstrate that mouse γc and the avian ortholog γc-a did not generate sγc. Moreover, two mouse isoforms, CRA-a and mγc-b, encoded by transcripts lacking a transmembrane region by alternative splicing, did not yield sγc. However, in ducks, sγc was produced from a γc-b transcript lacking a transmembrane region by alternative splicing. In chickens, sγc was produced in normal cells and cell lines by proteolytic shedding of the γc-b isoform containing intron 5, which displayed a relatively high probability of proteolytic cleavage of the ectodomain. This shedding was suppressed by leupeptin, serine and cysteine protease inhibitor. Compared to the chicken ortholog γc-a, expression of γc-b mRNA was differentially regulated according to tissue type, developmental stage, and antigen stimulation. These data demonstrate several mechanisms for producing sγc and suggest a potential role for sγc in avian lymphoid homeostatic responses to environmental antigens.
authors.affiliation: College of Veterinary Medicine & Institute of Animal Medicine, Gyeongsang National University, Jinju 660-701, South Korea.
authors.forename: Jipseol
authors.initials: J
authors.lastname: Jeong
authors.affiliation: College of Veterinary Medicine & Institute of Animal Medicine, Gyeongsang National University, Jinju 660-701, South Korea.
authors.forename: Woo H
authors.initials: WH
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine & Institute of Animal Medicine, Gyeongsang National University, Jinju 660-701, South Korea.
authors.forename: Cherry P
authors.initials: CP
authors.lastname: Fernandez
authors.affiliation: College of Veterinary Medicine & Institute of Animal Medicine, Gyeongsang National University, Jinju 660-701, South Korea.
authors.forename: Suk
authors.initials: S
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine & Institute of Animal Medicine, Gyeongsang National University, Jinju 660-701, South Korea.
authors.forename: Yong-Hwan
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Departments of Infectious Diseases and Avian Diseases, College of Veterinary Medicine & Korea Zoonosis Research Institute, Chonbuk National University, Jeonju 561-756, South Korea.
authors.forename: Hyung-Kwan
authors.initials: HK
authors.lastname: Jang
authors.affiliation: Animal Parasitic Diseases Laboratory, Animal and Natural Resources Institute, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA.
authors.forename: Hyun S
authors.initials: HS
authors.lastname: Lillehoj
authors.affiliation: Laboratory of Immunology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Hee-Jong
authors.initials: HJ
authors.lastname: Woo
authors.affiliation: College of Veterinary Medicine & Institute of Animal Medicine, Gyeongsang National University, Jinju 660-701, South Korea. Electronic address: wongimin@gnu.ac.kr.
authors.forename: Wongi
authors.initials: W
authors.lastname: Min
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002645:Chickens / Q000235:genetics / Q000276:immunology; D002522:Chlorocebus aethiops; D004372:Ducks / Q000235:genetics / Q000276:immunology; D016786:Eimeria tenella / Q000276:immunology*; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000096:biosynthesis* / Q000235:genetics; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D015398:Signal Transduction / Q000276:immunology
chemical_list: D053631:Interleukin Receptor Common gamma Subunit; D020033:Protein Isoforms
keywords: Common cytokine receptor γ chain; Ectodomain shedding; Shedding mechanisms; Soluble γ(c); γ(c)