CD45 and Src-related protein tyrosine kinases regulate the T cell response to phorbol esters.
CD45 and Src-related protein tyrosine kinases regulate the T cell response to phorbol esters.
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CD45 和 Src 相关蛋白酪氨酸激酶调节 T 细胞对佛波酯的反应。
DOI：
10.1006/bbrc.1998.8114
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发表时间：
1998
影响因子：
3.1
通讯作者：
Winfield,JB
中科院分区：
文献类型：
--
作者：
Czyzyk,JK;Fernsten,PD;Brtva,TR;Der,CJ;Winfield,JB
Ras 信号转导级联的蛋白激酶 C (PKC) 依赖性激活对于通过 T 细胞受体 (TCR) 刺激 T 淋巴细胞期间诱导 IL-2 启动子至关重要。在本研究中，在人 T 细胞中检查了 PKC 激活佛波醇肉豆蔻酸酯乙酸酯 (PMA) 对 ets/AP-1 Ras 响应启动子元件的 Ras 依赖性转录激活的影响。用 Src 家族 PTK 抑制剂除草霉素 A 预处理 Jurkat 细胞，与 PMA 孵育后报告基因的反式激活受到 50% 的抑制。还获得的证据表明，白细胞特异性蛋白酪氨酸磷酸酶 CD45（Src 样 PTK 的调节因子）参与了 PMA 诱导的 Ras/Raf 通路激活。首先，与 CD45 阳性细胞相比，PMA 诱导的 ets/AP-1 反式激活在 CD45 阴性变体中减少了 75%。其次，单克隆抗体与 CD45 的结合抑制了报告基因构建体的 PMA 反应。总而言之，这些数据表明 Src 相关蛋白介导 Ras/Raf 通路的 PKC 依赖性激活，并暗示 CD45 参与 PMA 等药物诱导的 T 淋巴细胞 TCR 独立激活。
Protein kinase C (PKC)-dependent activation of the Ras signal transduction cascade is essential for induction of the IL-2 promoter during stimulation of T lymphocytes via the T cell receptor (TCR). In this study, the effects of PKC-activating phorbol myristate acetate (PMA) on Ras-dependent activation of transcription from the ets/AP-1 Ras-responsive promoter element were examined in human T cells. Pretreatment of Jurkat cells with the Src-family PTK inhibitor herbimycin A resulted in a 50% inhibition of transactivation of the reporter following incubation with PMA. Evidence was also obtained to suggest the participation of the leukocyte-specific protein tyrosine phosphatase CD45, a regulator of Src-like PTKs, in the PMA-induced activation of the Ras/Raf pathway. First, PMA-induced transactivation of ets/AP-1 is diminished 75% in CD45-negative variants, compared with CD45-positive cells. Second, engagement of CD45 by monoclonal antibodies suppresses the PMA response from the reporter construct. Taken together, these data suggest that Src-related proteins mediate PKC-dependent activation of the Ras/Raf pathway and implicate CD45 in the TCR-independent activation of T lymphocytes induced by agents such as PMA.