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

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.
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