title: Differential requirement of the cytoplasmic subregions of gamma c chain in T cell development and function.
abstract: The common cytokine receptor gamma chain (gammac), a shared component of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15, is critical for the development and function of lymphocytes. The cytoplasmic domain of gammac consists of 85 aa, in which the carboxyl-terminal 48 aa are essential for its interaction with and activation of the Janus kinase, Jak3. Evidence has been provided that Jak3-independent signals might be transmitted via the residual membrane-proximal region; however, its role in vivo remains totally unknown. In the present study, we expressed mutant forms of gammac, which lack either most of the cytoplasmic domain or only the membrane-distal Jak3-binding region, on a gammac null background. We demonstrate that, unlike gammac or Jak3 null mice, expression of the latter, but not the former mutant, restores T lymphopoiesis in vivo, accompanied by strong expression of Bcl-2. On the other hand, the in vitro functions of the restored T cells still remained impaired. These results not only reveal the hitherto unknown role of the gammac membrane-proximal region, but also suggest the differential requirement of the cytoplasmic subregions of gammac in T cell development and function.
authors.affiliation: Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tsujino
authors.forename: J P
authors.initials: JP
authors.lastname: Di Santo
authors.forename: A
authors.initials: A
authors.lastname: Takaoka
authors.forename: T L
authors.initials: TL
authors.lastname: McKernan
authors.forename: S
authors.initials: S
authors.lastname: Noguchi
authors.forename: C
authors.initials: C
authors.lastname: Taya
authors.forename: H
authors.initials: H
authors.lastname: Yonekawa
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
authors.forename: H
authors.initials: H
authors.lastname: Fujii
mesh_terms: D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000276:immunology*; D017931:DNA Primers; D018076:DNA, Complementary; D005434:Flow Cytometry; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D019253:Proto-Oncogene Proteins c-bcl-2; D018123:Receptors, Interleukin; D011994:Recombinant Proteins