Buc H A, Moncion A, Hamet M, Perignon J L
Laboratoire de Biochimie Métabolique et Pharmacologique, INSERM U75, Faculté de Médecine Necker-Enfants Malades, Paris, France.
Int J Immunopharmacol. 1993 Apr;15(3):415-22. doi: 10.1016/0192-0561(93)90053-2.
We have examined in the human T-cell line Jurkat the interaction between the activation through the T-cell receptor/CD3 complex and the adenylate cyclase pathway. OKT3, an anti-CD3 monoclonal antibody, did not activate by itself adenylate cyclase but produced a 3-7-fold increase of the cAMP accumulation induced by indirect (chloroadenosine, PGE2) or direct (forskolin) agonists of adenylate cyclase. A more detailed study with forskolin showed that OKT3 enhanced the effect of low concentrations of the agonist without affecting the maximal capacity of cAMP synthesis of the cells. The same concentrations of OKT3 produced both the enhancement of the adenylate cyclase pathway and the activation of phospholipase C. The enhancement by OKT3 of the adenylate cyclase pathway was inhibited by 0.5 microM staurosporine, a potent inhibitor of protein kinases, including tyrosine kinases and protein kinase C, whereas it was not inhibited by H7, a specific inhibitor of PKC. Staurosporine, at the same concentration, also inhibited the OKT3-induced activation of phospholipase C, a tyrosine kinase-dependent process. Taken together, these data indicate that activation of T-cell through the T-cell receptor enhances the adenylate cyclase pathway by a tyrosine protein kinase-dependent mechanism.
我们已在人T细胞系Jurkat中研究了通过T细胞受体/CD3复合物的激活与腺苷酸环化酶途径之间的相互作用。抗CD3单克隆抗体OKT3本身不会激活腺苷酸环化酶，但会使由腺苷酸环化酶的间接（氯腺苷、前列腺素E2）或直接（福斯高林）激动剂诱导的cAMP积累增加3至7倍。用福斯高林进行的更详细研究表明，OKT3增强了低浓度激动剂的作用，而不影响细胞cAMP合成的最大能力。相同浓度的OKT3既增强了腺苷酸环化酶途径，又激活了磷脂酶C。OKT3对腺苷酸环化酶途径的增强作用被0.5微摩尔的星形孢菌素抑制，星形孢菌素是一种包括酪氨酸激酶和蛋白激酶C在内的蛋白激酶的有效抑制剂，而它不受PKC的特异性抑制剂H7的抑制。相同浓度的星形孢菌素也抑制了OKT3诱导的磷脂酶C的激活，这是一个酪氨酸激酶依赖性过程。综上所述，这些数据表明通过T细胞受体激活T细胞通过酪氨酸蛋白激酶依赖性机制增强了腺苷酸环化酶途径。
