Katagiri T, Urakawa K, Yamanashi Y, Semba K, Takahashi T, Toyoshima K, Yamamoto T, Kano K
Department of Immunology, University of Tokyo, Japan.
Proc Natl Acad Sci U S A. 1989 Dec;86(24):10064-8. doi: 10.1073/pnas.86.24.10064.
Overexpression of a src family gene, lck, has been associated with differentiation of the murine thymic lymphoma line LSTRA. Recent findings by several groups strongly suggest a functional role for the gene product p56lck protein-tyrosine kinase (PTK) in the activation of normal T cells. A single recessive gene, lpr or gld, induces a lymphoproliferative disorder concomitant with autoimmune disease in mice. In this study, a 10-fold elevated activity of PTK encoded by fyn, another src family gene, was demonstrated in CD4-CD8- T cells in mutant mice. The increased PTK activity was consistent with overexpression of fyn mRNA. The elevated fyn mRNA expression appeared to be a characteristic of CD4-CD8- T cells, since it was not observed in normal T cells at any stage of differentiation. The fact that fyn mRNA expression was markedly induced in normal T cells by mitogenic stimulation with anti-T3 epsilon antiserum supports the possibility that p59fyn PTK is a signal-generating molecule in T cells. Thus, our findings provide insight into the physiological role for a src gene family kinase in T-cell development and contribute to a better understanding of the molecular mechanisms of disease-inducing recessive genes.
src家族基因lck的过表达与小鼠胸腺淋巴瘤细胞系LSTRA的分化有关。几个研究小组最近的发现有力地表明，基因产物p56lck蛋白酪氨酸激酶（PTK）在正常T细胞的激活中具有功能性作用。单个隐性基因lpr或gld可在小鼠中诱发伴有自身免疫性疾病的淋巴细胞增生性疾病。在本研究中，另一个src家族基因fyn编码的PTK在突变小鼠的CD4-CD8-T细胞中活性升高了10倍。PTK活性的增加与fyn mRNA的过表达一致。fyn mRNA表达升高似乎是CD4-CD8-T细胞的一个特征，因为在正常T细胞分化的任何阶段都未观察到这种情况。用抗T3ε抗血清进行促有丝分裂刺激可在正常T细胞中显著诱导fyn mRNA表达，这一事实支持了p59fyn PTK是T细胞中信号产生分子的可能性。因此，我们的发现为src基因家族激酶在T细胞发育中的生理作用提供了见解，并有助于更好地理解诱发疾病的隐性基因的分子机制。
