A dominant-negative transgene defines a role for p56(lck) in thymopoiesis

Steven D. Levin, Steven J. Anderson, Katherine A. Forbush, Roger M. Perlmutter

Research output: Contribution to journalArticlepeer-review

293 Scopus citations

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 languageEnglish (US)
Pages (from-to)1671-1680
Number of pages10
JournalEMBO Journal
Volume12
Issue number4
DOIs
StatePublished - 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)

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