Transactivation of EGFR by G protein-coupled receptor in the pathophysiology of intimal hyperplasia.
Transactivation of EGFR by G protein-coupled receptor in the pathophysiology of intimal hyperplasia.
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DOI：
10.2174/1570161112666140226123745
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发表时间：
2014-02
影响因子：
4.5
通讯作者：
Swastika Sur;D. Agrawal
中科院分区：
文献类型：
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作者：
Swastika Sur;D. Agrawal
血管紧张素Ⅱ、凝血酶和ET-1、儿茶酚胺、血管紧张素Ⅱ、纤溶酶原激活剂和uPA等血管内皮细胞生长因子受体介导的EGFR受体反式激活，是血管损伤部位释放的血管紧张素Ⅱ、凝血酶和ET-1、儿茶酚胺、血管紧张素Ⅱ、纤溶酶原激活剂和uPA等促进血管内膜增殖的效应机制之一。EGFR的反式激活过程可以是同源配体依赖的，也可以是独立的。在同源配体依赖的反式激活中，配体结合的GPCR导致金属蛋白水解酶的激活，金属蛋白水解酶将膜系留生长因子与细胞外配体结合域上的EGFR结合，从而导致其反式激活。然而，在同源配体非依赖性反式激活中，配体结合的GPCR通过第二信使系统在细胞内激活EGFR。EGFR反式激活的机制取决于细胞类型、GPCRL和GPCR型。在这篇评论文章中，对这种交叉对话进行了批判性的讨论。EGFR的反式激活产生了导致各种病理状态的有丝分裂信号。这篇综述文章的目的是确定心血管系统内膜增生相关临床条件下治疗干预的潜在靶点。
GPCR-mediated receptor transactivation of EGFR, is one of the effector mechanisms by which GPCR ligands, such as Ang II, thrombin and ET -1, catecholamine, SII-angiotensin, PAF, and uPA that are released at the arterial injury sites, can potentiate intimal hyperplasia. The process of EGFR transactivation can be cognate ligand-dependent or independent. In cognate ligand- dependent transactivation, ligand-bound GPCR results in the activation of metalloproteases, which sheds membrane tethered growth factor that binds to EGFR on an extracellular ligand-binding domain causing its transactivation. Whereas, in cognate ligand independent transactivation, ligand bound GPCR activates EGFR intracellularly via second messenger system. The mechanism of EGFR transactivation depends on cell type, GPCR ligand and the type of GPCR. In this review article, such cross-talks are critically discussed. The EGFR transactivation generates mitogenic signals leading to various pathological conditions. The goal of this review article is to identify potential targets for therapeutic intervention in clinical conditions related to intimal hyperplasia in cardiovascular system.