A dominant‐negative transgene defines a role for p56lck in thymopoiesis.

SD Levin, SJ Anderson, KA Forbush… - The EMBO …, 1993 - embopress.org
SD Levin, SJ Anderson, KA Forbush, RM Perlmutter
The EMBO journal, 1993embopress.org
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 …
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 gamma/delta 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.
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