Abraham K M, Levin S D, Marth J D, Forbush K A, Perlmutter R M
Howard Hughes Medical Institute, University of Washington, Seattle 98195.
Proc Natl Acad Sci U S A. 1991 May 1;88(9):3977-81. doi: 10.1073/pnas.88.9.3977.
The lck gene encodes a membrane-associated protein tyrosine kinase (p56lck) that is believed to participate in lymphocyte-specific signal transduction pathways. To investigate the function of this molecule, transgenic mice were generated carrying the wild-type lck gene or a mutated lck gene encoding a constitutively activated form of p56lck (p56lckF505). Transgene expression in thymocytes was achieved in each case using the lck proximal promoter element. Mice expressing high levels of either p56lckF505 or p56lckY505 reproducibly developed thymic tumors. The sensitivity of thymocytes to p56lck-induced transformation suggests that disturbances in lck expression may contribute to the pathogenesis of some human neoplastic diseases.
lck基因编码一种膜相关蛋白酪氨酸激酶（p56lck），据信它参与淋巴细胞特异性信号转导途径。为了研究该分子的功能，构建了携带野生型lck基因或编码组成型激活形式p56lck（p56lckF505）的突变lck基因的转基因小鼠。在每种情况下，使用lck近端启动子元件在胸腺细胞中实现转基因表达。表达高水平p56lckF505或p56lckY505的小鼠可重复性地发生胸腺肿瘤。胸腺细胞对p56lck诱导的转化的敏感性表明，lck表达的紊乱可能有助于某些人类肿瘤性疾病的发病机制。
