...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >The S1P2 Receptor Negatively Regulates Platelet-Derived Growth Factor-Induced Motility and Proliferation
【24h】

The S1P2 Receptor Negatively Regulates Platelet-Derived Growth Factor-Induced Motility and Proliferation

机译：S1P2受体负调节血小板衍生的生长因子诱导的运动和增殖。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, is the ligand for five specific G protein-coupled receptors, named S1P1 to S1P5. In this study, we found that cross-communication between platelet-derived growth factor receptor and S1P2 serves as a negative damper of PDGF functions. Deletion of the S1P2 receptor dramatically increased migration of mouse embryonic fibroblasts toward S1P, serum, and PDGF but not fibronectin. This enhanced migration was dependent on expression of S1P1 and sphingosine kinase 1 (SphK1), the enzyme that produces S1P, as revealed by downregulation of their expression with antisense RNA and small interfering RNA, respectively. Although S1P2 deletion had no significant effect on tyrosine phosphorylation of the PDGF receptors or activation of extracellular signal-regulated kinase 1/2 or Akt induced by PDGF, it reduced sustained PDGF-dependent p38 phosphorylation and markedly enhanced Rac activation. Surprisingly, S1P2-null cells not only exhibited enhanced proliferation but also markedly increased SphK1 expression and activity. Conversely, reintroduction of S1P2 reduced DNA synthesis and expression of SphK1. Thus, S1P2 serves as a negative regulator of PDGF-induced migration and proliferation as well as SphK1 expression. Our results suggest that a complex interplay between PDGFR and S1P receptors determines their functions.
机译：具有生物活性的鞘脂代谢产物-1-磷酸鞘氨醇（S1P）是五个特定的G蛋白偶联受体的配体，称为S1P 1 至S1P 5 。在这项研究中，我们发现血小板衍生的生长因子受体与S1P 2 之间的交叉通讯是PDGF功能的负向抑制物。 S1P 2 受体的缺失显着增加了小鼠胚胎成纤维细胞向S1P，血清和PDGF（而非纤连蛋白）的迁移。这种增强的迁移依赖于产生S1P的酶S1P 1 和鞘氨醇激酶1（SphK1）的表达，这分别通过反义RNA和小干扰RNA的表达下调来揭示。尽管S1P 2 缺失对PDGF受体的酪氨酸磷酸化或PDGF诱导的细胞外信号调节激酶1/2或Akt的激活没有显着影响，但它减少了持续的PDGF依赖性p38磷酸化并显着增强Rac激活。令人惊讶的是，S1P 2 -无效细胞不仅显示出增强的增殖，而且还显着增加了SphK1的表达和活性。相反，重新引入S1P 2 会降低SphK1的DNA合成和表达。因此，S1P 2 充当PDGF诱导的迁移和增殖以及SphK1表达的负调节剂。我们的结果表明，PDGFR和S1P受体之间复杂的相互作用决定了它们的功能。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号