p21ras-induced responsiveness of phosphatidylinositol turnover to bradykinin is a receptor number effect.
p21ras-induced responsiveness of phosphatidylinositol turnover to bradykinin is a receptor number effect.
复制标题
p21ras 诱导的磷脂酰肌醇转换对缓激肽的反应是受体数量效应。
DOI：
10.1073/pnas.85.16.5774
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发表时间：
1988
影响因子：
11.1
通讯作者：
Weinberg,RA
中科院分区：
文献类型：
--
作者：
Downward,J;deGunzburg,J;Riehl,R;Weinberg,RA
由ras基因编码的蛋白质最近被报道将某些生长因子受体偶联到磷脂酶C上，磷脂酶C是催化磷脂酰肌醇分解的酶。为了验证这一假说，在强启动子的控制下，将正常和转化的Ha-、Ki-和N-ras基因分别转染到大鼠-1成纤维细胞中。选择了几种正常和转化的细胞系，表达高水平的p21ras。在这些细胞中测量磷脂酰肌醇的转换，以响应多种肽因子；与亲本细胞和对照细胞相比，缓激肽对p21ras过表达的影响大大增强。在这些细胞系中测量了缓激肽受体的数量，发现p21ras过表达细胞中的缓激肽受体数量比亲本细胞高出40倍。这被发现是所有三种ras基因的正常和转化形式的情况。在所有病例中，受体数量与缓激肽依赖性磷脂酰肌醇转换反应密切相关。这些数据表明，p21ras对细胞对肽激素缓激肽反应的影响是由于受体数量的变化，而不是p21ras在受体和磷脂酶C之间的直接偶联。
Proteins encoded by ras genes have recently been reported to couple certain growth factor receptors to phospholipase C, the enzyme catalyzing phosphatidylinositol breakdown. To investigate this hypothesis, the normal and the transforming Ha-, Ki-, and N-ras genes were each transfected into Rat-1 fibroblasts under the control of strong promoters. Several cell lines, both normal and transformed, were selected that expressed high levels of p21ras. Phosphatidylinositol turnover was measured in these cells in response to a wide variety of peptide factors; bradykinin was found to have a greatly enhanced effect on the p21ras overexpressors relative to the parental and control cells. Bradykinin receptor numbers were measured in these lines and found to be up to 40-fold higher in the p21ras overexpressors than in the parental cells. This was found to be the case for both normal and transforming forms of all three varieties of ras genes. Receptor number correlated well with the bradykinin-dependent phosphatidylinositol turnover response in all cases. These data indicate that the effects of p21ras on cellular responses to the peptide hormone bradykinin are due to changes in receptor number rather than to direct coupling by p21ras between the receptor and phospholipase C.