Altered Thymocyte Development Induced by Augmented Expression of p56lck

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Abstract

The lck gene encodes a lymphocyte-specific membrane associated protein tyrosine kinase (p56 lck ) that is implicated in T cell signal transduction by virtue of its physical association with CD4 and CD8 coreceptor molecules. To examine the role of this tyrosine kinase in thymocyte development, transgenic animals were produced which overexpress either wild-type p56lck, or an activated form of the lck kinase (p56 lckF505) under the control of the lck proximal promoter. The primary defect observed in lck transgenic animals is an alteration in normal thymopoiesis. In addition, animals expressing high levels of lck transgenes exhibit rapid thymoma development. These results suggest that regulation of p56lck activity is a critical feature of normal thymocyte development, and genetic mechanisms that are capable of altering this endogenous level of lck activity can lead to oncogenic transformation.