Kähne T, Neubert K, Ansorge S
Institute of Experimental Internal Medicine, University of Magdeburg, Germany.
Immunol Lett. 1995 May;46(1-2):189-93. doi: 10.1016/0165-2478(95)00041-3.
The T-cell activation antigen CD26 (dipeptidyl peptidase IV, DPIV) is a proline specific protease thought to be involved in regulation of the immune response. Several former results characterized this ectoenzyme as a possible accessory molecule of the T-cell surface. The molecular events of lymphocyte activation mediated by this enzyme, as well as the physiological ligands of dipeptidyl peptidase, are only partly established. Here we provide evidence for a direct involvement of DPIV/CD26 in early phosphorylation mechanisms which were known to be essential in the signal transduction cascade of human T lymphocytes. Considering a possible functional linkage between CD26 and the tyrosine kinase p56lck, we have investigated the action of DPIV-specific inhibitors (Lys[Z[NO2)]-thiazolidide and -piperidide) on the PMA-induced hyperphosphorylation of p56lck in human T cells. Interestingly, this hyperphosphorylation of p56lck was strongly suppressed by both inhibitors in a dose-dependent manner. Removal of these inhibitors totally restored the hyperphosphorylation. Therefore, this effect could be considered as reversible. Free thiazolidine and piperidine, used in control experiments, neither inhibit DPIV enzyme activity nor PMA-induced hyperphosphorylation. The data presented here provide evidence that DPIV/CD26 is directly involved in early processes of T-cell activation. Furthermore, these findings strongly support the assumption that the signaling function of CD26 requires its enzymatic activity.
T细胞活化抗原CD26（二肽基肽酶IV，DPIV）是一种脯氨酸特异性蛋白酶，被认为参与免疫反应的调节。先前的一些研究结果将这种胞外酶表征为T细胞表面一种可能的辅助分子。由该酶介导的淋巴细胞活化的分子事件以及二肽基肽酶的生理配体仅部分得到确定。在这里，我们提供证据表明DPIV/CD26直接参与早期磷酸化机制，而早期磷酸化机制在人类T淋巴细胞的信号转导级联反应中至关重要。考虑到CD26与酪氨酸激酶p56lck之间可能存在功能联系，我们研究了DPIV特异性抑制剂（Lys[Z(NO2)]-噻唑烷和哌啶）对人T细胞中佛波酯（PMA）诱导的p56lck过度磷酸化的作用。有趣的是，这两种抑制剂均以剂量依赖的方式强烈抑制了p56lck的过度磷酸化。去除这些抑制剂后，过度磷酸化完全恢复。因此，这种作用可被认为是可逆的。在对照实验中使用的游离噻唑烷和哌啶既不抑制DPIV酶活性，也不抑制PMA诱导的过度磷酸化。本文提供的数据证明DPIV/CD26直接参与T细胞活化的早期过程。此外，这些发现有力地支持了CD26的信号传导功能需要其酶活性这一假设。
