A dominant-negative transgene defines a role for p56lck in thymopoiesis

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

Research output: Contribution to journalArticlepeer-review

306 Scopus citations


The lymphocyte-specific protein tyrosine kinase p56lck 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 p56lck has now been obtained through the generation of transgenic animals expressing high levels of a catalytically inactive form of this kinase (p56lckR273). 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 p56lck 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
Issue number4
StatePublished - 1993


  • T cells
  • Thymopoiesis
  • p56

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • Molecular Biology
  • General Neuroscience


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