First Author | Tsujino S | Year | 2000 |
Journal | Proc Natl Acad Sci U S A | Volume | 97 |
Issue | 19 | Pages | 10514-9 |
PubMed ID | 10962026 | Mgi Jnum | J:92738 |
Mgi Id | MGI:3054373 | Doi | 10.1073/pnas.180063297 |
Citation | Tsujino S, et al. (2000) Differential requirement of the cytoplasmic subregions of gamma c chain in T cell development and function. Proc Natl Acad Sci U S A 97(19):10514-9 |
abstractText | 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. |