• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Signalling >Protease activated receptor-1 mediated dual kinase receptor transactivation stimulates the expression of glycosaminoglycan synthesizing genes
【24h】

Protease activated receptor-1 mediated dual kinase receptor transactivation stimulates the expression of glycosaminoglycan synthesizing genes

机译：蛋白酶激活受体-1介导的双激酶受体反式激活刺激糖胺聚糖合成基因的表达

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

G protein-coupled receptors (GPCR) are one of the most important targets for therapeutics due to their abundance and diversity. The G protein-coupled receptor for thrombin can transactivate protein tyrosine kinase receptors (PTKR) and we have recently established that it can also transactivate serine/threonine kinase receptors (S/TKR). A comprehensive knowledge of the signalling pathways that GPCR transactivation elicits is necessary to fully understand the implications of both GPCR activation and the impact of target drugs. Here, we demonstrate that thrombin elicits dual transactivation-dependent signalling pathways to stimulate mRNA expression of glycosaminoglycan synthesizing enzymes chondroitin 4-O-sulfotransferase 1 and chondroitin sulfate synthase 1. The PTKR mediated response involves matrix metalloproteinases and the phosphorylation of the MAP kinase Erk. The S/TKR mediated response differs markedly and involves the phosphorylation of Smad2 carboxy terminal serine residues and does not involve matrix metalloproteinases. This work shows that all of the thrombin mediated signalling to glycosaminoglycan synthesizing enzyme gene expression occurs via transactivation-dependent pathways and does not involve transactivation-independent signalling. These findings highlight the complexity of thrombin-mediated transactivation signalling and the broader implications of GPCR targeted therapeutics. (C) 2015 Elsevier Inc. All rights reserved.
机译：G蛋白偶联受体（GPCR）由于其丰富性和多样性而成为治疗学最重要的靶标之一。凝血酶的G蛋白偶联受体可以激活蛋白酪氨酸激酶受体（PTKR），我们最近已经确定它还可以激活丝氨酸/苏氨酸激酶受体（S / TKR）。要全面了解GPCR激活的含义和靶标药物的影响，必须全面了解GPCR激活引起的信号传导途径。在这里，我们证明了凝血酶引发双重依赖于转录的信号转导途径，以刺激糖胺聚糖合成酶软骨素4-O-磺基转移酶1和硫酸软骨素合酶1的mRNA表达。PTKR介导的应答涉及基质金属蛋白酶和MAP激酶Erk的磷酸化。 S / TKR介导的反应明显不同，并且涉及Smad2羧基末端丝氨酸残基的磷酸化，并且不涉及基质金属蛋白酶。这项工作表明，凝血酶介导的向糖胺聚糖合成酶基因表达的所有信号传导均通过反式激活依赖性途径发生，并且不涉及非反式激活信号。这些发现突出了凝血酶介导的反式激活信号的复杂性以及GPCR靶向治疗剂的广泛含义。 （C）2015 Elsevier Inc.保留所有权利。

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