Joyal Jean-Sébastien, Bhosle Vikrant K, Chemtob Sylvain
Université de Montréal, CHU Ste-Justine Hospital Research Centre, Departments of Pediatrics, Ophthalmology and Pharmacology , 3175 Côte Ste-Catherine, Montréal, Qc, H3T 1C5 , Canada +1 514 345 4931 Ext. 2978 ; +1 514 345 4801 ;
Expert Opin Ther Targets. 2015 Jun;19(6):717-21. doi: 10.1517/14728222.2015.1042365.
G-protein coupled receptors (GPCRs) evolved as specialized sensors of the extracellular environment. Comprising the largest family of cell surface receptors, GPCRs are common therapeutic targets. Over the last 25 years, several GPCRs have been observed at the cell nucleus, suggesting the presence of intracrine GPCR signaling beyond the plasma membrane. Yet specific physiological functions of nuclear GPCRs had not been reported, until lately. We recently uncovered distinct but complementary angiogenic roles of F2rl1 (formerly known as PAR2) depending on its subcellular localization at the plasma membrane or at the nucleus. Targeting subcellular compartments to improve drug selectivity may therefore inspire novel therapeutic strategies for transmembrane receptors.
G蛋白偶联受体（GPCRs）作为细胞外环境的特殊传感器而进化。GPCRs是最大的细胞表面受体家族，是常见的治疗靶点。在过去25年中，人们在细胞核中观察到了几种GPCRs，这表明在质膜之外存在内分泌GPCR信号传导。然而，直到最近，核GPCRs的具体生理功能尚未见报道。我们最近发现，F2rl1（以前称为PAR2）根据其在质膜或细胞核中的亚细胞定位具有不同但互补的血管生成作用。因此，靶向亚细胞区室以提高药物选择性可能会激发针对跨膜受体的新型治疗策略。
