Cooke M P, Abraham K M, Forbush K A, Perlmutter R M
Howard Hughes Medical Institute, University of Washington, Seattle 98195.
Cell. 1991 Apr 19;65(2):281-91. doi: 10.1016/0092-8674(91)90162-r.
Engagement of the clonotypic antigen receptor (TCR) on T lymphocytes provokes an activation response leading to cell proliferation and lymphokine secretion. To examine the molecular basis of T cell signaling, we generated transgenic animals in which a lymphocyte-specific nonreceptor protein-tyrosine kinase p59fyn(T) is 20-fold overexpressed in developing T lineage cells. Thymocytes from these mice, analyzed using both cellular and biochemical assays, were remarkably hyperstimulable. Moreover, the responsiveness of normal thymocytes to TCR-derived signals correlated well with the extent to which p59fyn was expressed in these cells. Overexpression of a catalytically inactive form of p59fyn substantially inhibited TCR-mediated activation in otherwise normal thymocytes. These effects are unique to p59fyn; overexpression of a closely related T cell-specific tyrosine kinase, p56lck, elicits dramatically different phenotypes. Our results suggest that p59fyn is a critically important component of the TCR signal transduction apparatus.
T淋巴细胞上克隆型抗原受体（TCR）的激活引发了导致细胞增殖和淋巴因子分泌的激活反应。为了研究T细胞信号传导的分子基础，我们构建了转基因动物，其中淋巴细胞特异性非受体蛋白酪氨酸激酶p59fyn(T)在发育中的T系细胞中过表达20倍。使用细胞和生化分析方法对这些小鼠的胸腺细胞进行分析，发现它们具有显著的高反应性。此外，正常胸腺细胞对TCR衍生信号的反应性与p59fyn在这些细胞中的表达程度密切相关。在原本正常的胸腺细胞中，催化失活形式的p59fyn过表达会显著抑制TCR介导的激活。这些效应是p59fyn所特有的；密切相关的T细胞特异性酪氨酸激酶p56lck过表达会引发截然不同的表型。我们的结果表明，p59fyn是TCR信号转导装置的一个至关重要的组成部分。
