Cross-linking of CD26 by antibody induces tyrosine phosphorylation and activation of mitogen-activated protein kinase
Cross-linking of CD26 by antibody induces tyrosine phosphorylation and activation of mitogen-activated protein kinase
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DOI：
10.1046/j.1365-2567.1997.00053.x
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发表时间：
1997-02-01
期刊：
影响因子：
6.4
通讯作者：
Morimoto, C
中科院分区：
文献类型：
--
作者：
Hegen, M;Kameoka, J;Morimoto, C
CD26是一种t细胞活化抗原，其胞外结构域具有二肽基肽酶IV活性，并在t细胞活化中发挥重要作用。在受刺激的T淋巴细胞中，通过T细胞受体（TCR）的参与而激活的最早生化事件是一组细胞蛋白的酪氨酸磷酸化。在这项研究中，我们证明了在CD26转染的Jurkat细胞中，抗体诱导的CD26交联诱导了几种细胞内蛋白的酪氨酸磷酸化，其模式与TCR/CD3刺激后的模式相似。Herbimycin A是src家族蛋白酪氨酸激酶的抑制剂，可显著抑制cd26介导的酪氨酸磷酸化作用。免疫印迹法鉴定了主要酪氨酸磷酸化蛋白，包括p56（lck）、p59（fyn）、zeta相关蛋白- 70000 MW酪氨酸激酶（ZAP-70）、丝裂原活化蛋白激酶（MAP）、C - cbl和磷脂酶C γ。cd26诱导的MAP激酶酪氨酸磷酸化与MAP激酶活性增加相关。此外，与单独激活CD3相比，CD26和CD3抗原共交联诱导酪氨酸磷酸化延长和增加，因此CD26对CD3信号转导具有共刺激作用。因此，我们得出结论，CD26是一个真正的共刺激实体，可以上调TCR的信号转导特性。
CD26, a T-cell activation antigen that has dipeptidyl peptidase IV activity in its extracellular domain and has also been shown to play an important role in T-cell activation. The earliest biochemical events seen in stimulated T lymphocytes activated through the engagement of the T-cell receptor (TCR) is the tyrosine phosphorylation of a panel of cellular proteins. In this study we demonstrate that antibody-induced cross-linking of CD26 in CD26-transfected Jurkat cells induced tyrosine phosphorylation of several intracellular proteins with a similar pattern to that seen after TCR/CD3 stimulation. Herbimycin A, an inhibitor of the src family protein tyrosine kinases dramatically inhibited this CD26-mediated effect on tyrosine phosphorylation. Major tyrosine phosphorylated proteins were identified by immunoblotting, and included p56(lck), p59(fyn), zeta associated protein-tyrosine kinase of 70000 MW (ZAP-70), mitogen-activated protein (MAP) kinase, c-Cbl, and phospholipase C gamma. CD26-induced tyrosine phosphorylation of MAP kinase correlated with increased MAP kinase activity. In addition, CD26 was costimulatory to CD3 signal transduction since co-cross-linking of CD26 and CD3 antigens induced prolonged and increased tyrosine phosphorylation in comparison with CD3 activation alone. We therefore conclude that CD26 is a true costimulatory entity that can up-regulate the signal transducing properties of the TCR.