Sur Swastika, Agrawal Devendra K
Center for Clinical & Translational Science, Creighton University School of Medicine, CRISS II Room 510, 2500 California Plaza, Omaha, NE 68178, USA.
Curr Vasc Pharmacol. 2014 Mar;12(2):190-201. doi: 10.2174/1570161112666140226123745.
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.
G蛋白偶联受体（GPCR）介导的表皮生长因子受体（EGFR）转活化，是GPCR配体（如在动脉损伤部位释放的血管紧张素II、凝血酶、内皮素-1、儿茶酚胺、SII-血管紧张素、血小板活化因子和尿激酶型纤溶酶原激活剂）增强内膜增生的效应机制之一。EGFR转活化过程可以是同源配体依赖性的或非依赖性的。在同源配体依赖性转活化中，与配体结合的GPCR导致金属蛋白酶激活，金属蛋白酶切割膜结合的生长因子，该生长因子在细胞外配体结合域与EGFR结合，导致其转活化。而在同源配体非依赖性转活化中，与配体结合的GPCR通过第二信使系统在细胞内激活EGFR。EGFR转活化的机制取决于细胞类型、GPCR配体和GPCR的类型。在这篇综述文章中，将对这种相互作用进行批判性讨论。EGFR转活化产生促有丝分裂信号，导致各种病理状况。这篇综述文章的目的是确定在与心血管系统内膜增生相关的临床病症中进行治疗干预的潜在靶点。
