Role of protein kinase C in diacylglycerol-mediated induction of ornithine decarboxylase and reduction of epidermal growth factor binding.
Role of protein kinase C in diacylglycerol-mediated induction of ornithine decarboxylase and reduction of epidermal growth factor binding.
复制标题
蛋白激酶 C 在二酰基甘油介导的鸟氨酸脱羧酶诱导和表皮生长因子结合减少中的作用。
DOI：
10.1073/pnas.82.7.1941
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发表时间：
1985
影响因子：
11.1
通讯作者：
Bell,RM
中科院分区：
文献类型：
--
作者：
Jetten,AM;Ganong,BR;Vandenbark,GR;Shirley,JE;Bell,RM
促肿瘤佛波酯诱导大鼠气管上皮2C5细胞鸟氨酸脱羧酶(ODCase)活性和减少表皮生长因子(EGF)结合。佛波酯通过与推测的生理调节剂sn-1，2-二酰基甘油在同一位置相互作用来激活蛋白激酶C。本实验研究了添加sn-1，2-二酰甘油和磷脂酶C对2C5细胞ODCase诱导和EGF结合的影响，以确定蛋白激酶C在这些细胞反应中的作用。2C5细胞经磷脂酶C处理后，ODCase活性升高，EGF结合量减少，而磷脂酶A2和D则失活。在2C5细胞中加入含3-10个碳脂肪酸的SN-1，2-二酰基甘油，可引起ODCase的诱导和EGF结合的减少。SN-1，2-二辛酰甘油是活性最高的化合物之一。它以剂量(50-500微米)和时间依赖的方式诱导ODCase。Sn-1，2-二辛酰甘油降低~(125)I标记的EGF的结合也是时间和剂量依赖性的，似乎是由于EGF亲和力的改变而不是受体位置的改变。这一系列SN-1，2-二酰基甘油在诱导ODCase活性、减少EGF结合、刺激蛋白激酶C和抑制[~3H]佛波二丁酸酯与佛波酯受体结合的能力方面表现出相似的结构-功能关系。这些数据显示了一些二酰甘油的生物活性，并表明蛋白激酶C的激活与ODCase的诱导和EGF结合的减少有关。
Tumor-promoting phorbol esters induce ornithine decarboxylase (ODCase) activity and reduce epidermal growth factor (EGF) binding in rat tracheal epithelial 2C5 cells. Phorbol esters activate protein kinase C by interacting at the same site as sn-1,2-diacylglycerols, the presumed physiological regulators. The effects of added sn-1,2-diacylglycerols and those generated by phospholipase C treatment of 2C5 cells on ODCase induction and EGF binding were investigated to establish a role for protein kinase C in these cellular responses. Treatment of 2C5 cells with phospholipase C induced ODCase activity and reduced EGF binding, whereas phospholipases A2 and D were inactive. When sn-1,2-diacylglycerols containing fatty acids 3-10 carbons in length were added to 2C5 cells, those diacylglycerols containing fatty acids 5-10 carbons in length caused ODCase induction and reduction in EGF binding. sn-1,2-Dioctanoylglycerol was one of the most active compounds tested. It induced ODCase in a dose- (50-500 microM) and time-dependent manner. The reduction of binding of 125I-labeled EGF by sn-1,2-dioctanoylglycerol was also time and dose dependent and appeared to result from a change in EGF affinity and not the number of receptor sites. This series of sn-1,2-diacylglycerols showed similar structure-function relationships in their ability to induce ODCase activity, to decrease EGF binding, to stimulate protein kinase C, and to inhibit [3H]phorbol dibutyrate binding to the phorbol ester receptor. These data demonstrate biological activities for a number of diacylglycerols and indicate that protein kinase C activation is implicated in ODCase induction and decreased EGF binding.