MECHANISM OF ACTION OF THE PHORBOL ESTER TUMOR PROMOTERS - SPECIFIC RECEPTORS FOR LIPOPHILIC LIGANDS
MECHANISM OF ACTION OF THE PHORBOL ESTER TUMOR PROMOTERS - SPECIFIC RECEPTORS FOR LIPOPHILIC LIGANDS
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DOI：
10.1016/0006-2952(84)90448-9
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发表时间：
1984-01-01
影响因子：
5.8
通讯作者：
YEH, E
中科院分区：
文献类型：
--
作者：
BLUMBERG, PM;JAKEN, S;YEH, E
细胞和组织制剂特异性结合磷酯肿瘤促进剂。结合位点与生物反应之间的结构-活性关系一致，有力地证明了这些结合位点具有磷酯受体的功能。亚细胞分离后，磷酯结合活性呈颗粒状。此外，在需要磷脂重建的细胞质中可以检测到一种磷酸酯载脂蛋白受体。这种载脂蛋白受体似乎与蛋白激酶C相对应。二酰基甘油，可能是蛋白激酶C的天然激活剂，竞争性地抑制磷酸酯的结合，与假设的内源性磷酸酯类似物相一致。在某些体系中，发现了磷酯结合的不均匀性。因此，一个突出的问题是，蛋白激酶C是酚酯受体，还是仅仅是最丰富的一类受体。虽然这个问题仍未解决，但我们可以通过在异质脂质环境中重组载脂蛋白受体来证明磷酯结合的异质性。
Cells and tissue preparations specifically bind the phorbol ester tumor promoters. The agreement in structure-activity relationships between binding and biological response strongly argues that these binding sites function as phorbol ester receptors. Upon subcellular fractionation, the phorbol ester binding activity is particulate. In addition, a phorbol ester apo-receptor can be detected in cytosol which requires phospholipids for reconstitution. This apo-receptor appears to correspond to protein kinase C. Diacylglycerols, the probable natural activators of protein kinase C, competitively inhibit phorbol ester binding, consistent with their being the postulated endogenous phorbol ester analogs. In certain systems, heterogeneity of phorbol ester binding is found. An outstanding issue therefore is whether protein kinase C isthephorbol ester receptor or whether it is only the most abundant class of receptor. Although this question remains unresolved, we can demonstrate heterogeneity of phorbol ester binding by reconstitution of apo-receptor into a heterogeneous lipid environment.