Differential requirement of the cytoplasmic subregions of gamma c chain in T cell development and function.
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.
Tsujino
S
S
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Di Santo
J P
JP
Takaoka
A
A
McKernan
T L
TL
Noguchi
S
S
Taya
C
C
Yonekawa
H
H
Saito
T
T
Taniguchi
T
T
Fujii
H
H
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*
D017931:DNA Primers; D018076:DNA, Complementary; D019253:Proto-Oncogene Proteins c-bcl-2; D018123:Receptors, Interleukin; D011994:Recombinant Proteins