Stewart S J, Cunningham G R, House F S
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN.
Cell Signal. 1993 May;5(3):315-23. doi: 10.1016/0898-6568(93)90022-e.
Perturbation of the T lymphocyte antigen receptor/CD3 complex or phorbol ester stimulation leads to activation of phospholipase D in the Jurkat T lymphocyte cell line. These observations suggested that phospholipase D activation might result from activation of protein kinase C. In other systems, phospholipase D activity has been shown to be under G-protein or protein kinase C control. Studies detailed here demonstrate that commonly used inhibitors of protein kinase C had unrelated, diverse effects on phospholipase D activity in T lymphocytes. However, protein kinase C down-regulation resulting from prolonged cellular exposure to phorbol esters led to abrogation of anti-CD3-stimulated phospholipase D activation. The results presented underline the complexity of studies employing inhibitors of protein kinase C, suggest interesting approaches to isolation of phospholipase D dependent signalling pathways, confirm that T cell antigen receptor-linked activation of phospholipase D is dependent upon protein kinase C activity and suggest that distant events of T lymphocyte activation are dependent upon the establishment of a positive feedback loop involving protein kinase C and phospholipase D which would result in the prolonged activation of protein kinase C required for certain lymphokine production.
T淋巴细胞抗原受体/CD3复合物的扰动或佛波酯刺激可导致Jurkat T淋巴细胞系中磷脂酶D的激活。这些观察结果表明，磷脂酶D的激活可能源于蛋白激酶C的激活。在其他系统中，磷脂酶D的活性已被证明受G蛋白或蛋白激酶C的控制。此处详述的研究表明，常用的蛋白激酶C抑制剂对T淋巴细胞中磷脂酶D的活性具有不相关的、多样的影响。然而，由于细胞长期暴露于佛波酯而导致的蛋白激酶C下调，导致抗CD3刺激的磷脂酶D激活被消除。所呈现的结果强调了使用蛋白激酶C抑制剂进行研究的复杂性，提出了分离磷脂酶D依赖性信号通路的有趣方法，证实了T细胞抗原受体相关的磷脂酶D激活依赖于蛋白激酶C的活性，并表明T淋巴细胞激活的远距离事件依赖于涉及蛋白激酶C和磷脂酶D的正反馈回路的建立，这将导致某些淋巴因子产生所需的蛋白激酶C的长期激活。
