Abstract
The lymphocyte-specific protein tyrosine kinase p56(lck) participates in T cell signaling through functional interactions with components of the T cell antigen receptor complex and the interleukin-2 receptor. Additional insight into the function of p56(lck) has now been obtained through the generation of transgenic animals expressing high levels of a catalytically inactive form of this kinase (p56(lckR273)). Mice bearing the lckR273 transgene manifested a severe defect in the production of virtually all T lymphocytes. Those exceptional CD3+ cells that escaped the effects of the lckR273 transgene were confined primarily to the T cell subset that expresses γ/δ T cell receptors. Remarkably, construction of a dose-response curve for the effects of the lckR273 transgene revealed that developmental arrest of thymocytes occurred at a discrete stage in the normal T cell maturation pathway, corresponding to a point at which thymoblasts ordinarily begin a series of mitotic divisions that result in expansion and maturation. These results suggest that p56(lck) normally regulates T cell production by metering the replicative potential of immature thymoblasts.
Original language | English (US) |
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Pages (from-to) | 1671-1680 |
Number of pages | 10 |
Journal | EMBO Journal |
Volume | 12 |
Issue number | 4 |
DOIs | |
State | Published - 1993 |
Keywords
- T-cells
- Thymopoiesis
- p56(lck)
ASJC Scopus subject areas
- Neuroscience(all)
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)