Levin S D, Anderson S J, Forbush K A, Perlmutter R M
Howard Hughes Medical Institute, University of Washington, Seattle 98195.
EMBO J. 1993 Apr;12(4):1671-80. doi: 10.1002/j.1460-2075.1993.tb05812.x.
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.
淋巴细胞特异性蛋白酪氨酸激酶p56lck通过与T细胞抗原受体复合物和白细胞介素-2受体的成分进行功能相互作用，参与T细胞信号传导。现在，通过生成表达这种激酶催化失活形式（p56lckR273）的转基因动物，对p56lck的功能有了进一步的了解。携带lckR273转基因的小鼠在几乎所有T淋巴细胞的产生方面表现出严重缺陷。那些不受lckR273转基因影响的特殊CD3+细胞主要局限于表达γ/δT细胞受体的T细胞亚群。值得注意的是，构建lckR273转基因效应的剂量反应曲线表明，胸腺细胞的发育停滞发生在正常T细胞成熟途径中的一个离散阶段，对应于成胸腺细胞通常开始一系列有丝分裂的点，这些有丝分裂会导致细胞扩增和成熟。这些结果表明，p56lck通常通过计量未成熟成胸腺细胞的复制潜力来调节T细胞的产生。
