Mohamed Raafat, Janke Reearna, Guo Wanru, Cao Yingnan, Zhou Ying, Zheng Wenhua, Babaahmadi-Rezaei Hossein, Xu Suowen, Kamato Danielle, Little Peter J
School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Woolloongabba, Queensland, Australia.
Department of Basic Sciences, College of Dentistry, University of Mosul, Mosul, Iraq.
Vasc Biol. 2019 Jul 23;1(1):R1-R11. doi: 10.1530/VB-18-0004. eCollection 2019.
The discovery and extension of G-protein-coupled receptor (GPCR) transactivation-dependent signalling has enormously broadened the GPCR signalling paradigm. GPCRs can transactivate protein tyrosine kinase receptors (PTKRs) and serine/threonine kinase receptors (S/TKRs), notably the epidermal growth factor receptor (EGFR) and transforming growth factor-β type 1 receptor (TGFBR1), respectively. Initial comprehensive mechanistic studies suggest that these two transactivation pathways are distinct. Currently, there is a focus on GPCR inhibitors as drug targets, and they have proven to be efficacious in vascular diseases. With the broadening of GPCR transactivation signalling, it is therefore important from a therapeutic perspective to find a common transactivation pathway of EGFR and TGFBR1 that can be targeted to inhibit complex pathologies activated by the combined action of these receptors. Reactive oxygen species (ROS) are highly reactive molecules and they act as second messengers, thus modulating cellular signal transduction pathways. ROS are involved in different mechanisms of GPCR transactivation of EGFR. However, the role of ROS in GPCR transactivation of TGFBR1 has not yet been studied. In this review, we will discuss the involvement of ROS in GPCR transactivation-dependent signalling.
G蛋白偶联受体（GPCR）反式激活依赖性信号传导的发现与拓展极大地拓宽了GPCR信号传导范式。GPCR可分别反式激活蛋白酪氨酸激酶受体（PTKR）和丝氨酸/苏氨酸激酶受体（S/TKR），特别是表皮生长因子受体（EGFR）和转化生长因子-β1型受体（TGFBR1）。最初的全面机制研究表明这两条反式激活途径是不同的。目前，人们聚焦于将GPCR抑制剂作为药物靶点，并且已证明它们在血管疾病中有效。随着GPCR反式激活信号传导的拓展，因此从治疗角度来看，找到EGFR和TGFBR1的共同反式激活途径以靶向抑制由这些受体联合作用激活的复杂病理状况很重要。活性氧（ROS）是高反应性分子，它们作为第二信使，从而调节细胞信号转导途径。ROS参与EGFR的GPCR反式激活的不同机制。然而，ROS在TGFBR1的GPCR反式激活中的作用尚未得到研究。在本综述中，我们将讨论ROS在GPCR反式激活依赖性信号传导中的作用。
