Differential requirement of the cytoplasmic subregions of gamma c chain in T cell development and function

Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10514-9. doi: 10.1073/pnas.180063297.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • COS Cells
  • Cell Membrane / metabolism
  • Cytoplasm / immunology*
  • DNA Primers
  • DNA, Complementary
  • Flow Cytometry
  • Mice
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / immunology*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*

Substances

  • DNA Primers
  • DNA, Complementary
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Interleukin
  • Recombinant Proteins