Effects of EGF and thrombin on inositol‐containing phospholipids of cultured fibroblasts: Stimulation of phosphatidylinositol synthesis by thrombin but not EGF
Effects of EGF and thrombin on inositol‐containing phospholipids of cultured fibroblasts: Stimulation of phosphatidylinositol synthesis by thrombin but not EGF
复制标题
DOI：
10.1002/jcp.1041250330
复制
发表时间：
1985-12
影响因子：
5.6
通讯作者：
D. Raben;D. Cunningham
中科院分区：
文献类型：
--
作者：
D. Raben;D. Cunningham
研究了生长因子对含肌醇磷脂的影响，以验证其代谢改变参与有丝分裂刺激的假设。凝血酶和EGF在有丝分裂对这两种生长因子都有反应的细胞系中刺激了磷脂酰肌醇4 -单磷酸（DPI）和磷脂酰肌醇4,5 -二磷酸（TPI）的合成（30-50%）和降解（20-40%）的相应增加。合成的增加是时间和剂量依赖性的，这与它们参与有丝分裂是一致的；只有在有丝分裂反应发生的情况下才观察到这种增加。虽然有人认为磷脂酰肌醇（PI）合成的增加与DPI和TPI合成的刺激有关，但我们发现凝血酶刺激了PI的早期合成，而EGF没有。为了进一步评估PI参与凝血酶刺激的细胞分裂，我们确定了受刺激的PI合成的时间和剂量依赖性，并发现它也以与其参与凝血酶刺激的细胞分裂的方式发生。此外，在非有丝分裂蛋白酶或对凝血酶无反应的细胞系中，未观察到受刺激的PI合成。这些结果表明DPI和TPI的代谢似乎与EGF和凝血酶产生的有丝分裂反应密切相关。然而，早期刺激PI合成并不与这种代谢相结合，也不是EGF刺激有丝分裂所必需的。因此，刺激PI合成并不能有效测量含肌醇磷脂的改变，也就是所谓的“PI反应”。
The effects of growth factors on inositol‐containing phospholipids were investigated to test the hypothesis that alterations in their metabolism are involved in mitogenic stimulation. Thrombin and EGF stimulated comparable increases in the synthesis (30–50%) and degradation (20–40%) of phosphatidylinositol 4‐monophosphate (DPI) and phosphatidylinositol 4,5‐bisphosphate (TPI) in a cell line which is mitogenically responsive to both growth factors. The increases in synthesis were time and dose dependent in a manner which was consistent with their involvement in mitogenesis; the increases were observed only under conditions where a mitogenic response occurred. While it has been suggested that an increased synthesis of phosphatidylinositol (PI) is coupled to the stimulation of DPI and TPI synthesis, we found that thrombin stimulated an early synthesis PI but EGF did not. To further evaluate the involvement of PI in thrombin‐stimulated cell division we determined the time and dose dependence of the stimulated PI synthesis and found that it also occurred in a manner which was consistent with its involvement in thrombin‐stimulated cell division. Furthermore, the stimulated PI synthesis was not observed with nonmitogenic proteases or in cell lines which were not responsive to thrombin. These results demonstrate that the metabolism of DPI and TPI appears closely related to the mitogenic response generated by EGF and thrombin. However, an early stimulation of PI synthesis is not coupled to this metabolism and is not necessary for mitogenic stimulation by EGF. Thus, a stimulation of PI synthesis is not a valid measure of alterations in inositol‐containing phospholipids and what has been termed the “PI response.”