Structure, Function, Pharmacology, and Therapeutic Potential of the G Protein, Gα/q,11.
Structure, Function, Pharmacology, and Therapeutic Potential of the G Protein, Gα/q,11.
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DOI：
10.3389/fcvm.2015.00014
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发表时间：
2015
影响因子：
3.6
通讯作者：
Little PJ
中科院分区：
文献类型：
--
作者：
Kamato D;Thach L;Bernard R;Chan V;Zheng W;Kaur H;Brimble M;Osman N;Little PJ
G蛋白偶联受体（GPCR）是细胞表面受体的主要类别之一，并且与由称为α、β和γ的三个亚基组成的一组G蛋白相关。G蛋白根据其α亚基分为四个家族：Gαi、Gαs、Gα12/13和Gαq。Gαq有几种下游途径，其中最为人所知的是通过三磷酸鸟苷（GTP）激活，Gαq激活磷脂酶Cβ，将磷脂酰肌醇4，5-二磷酸水解为二酰基甘油和三磷酸肌醇，激活蛋白激酶C并增加内质网的钙流出。虽然G蛋白，特别是Gαq/11是GPCR信号转导的核心元件，但它们的实际作用尚未得到彻底研究。缺乏对Gαq/11在细胞生物学中作用的研究，部分原因是现有药理学试剂的性质不明确。YM-254890是最有用的Gα q选择性抑制剂，具有抗血小板、抗血栓形成和溶栓作用。YM-254890通过阻止鸟苷二磷酸交换为GTP来抑制Gαq信号通路。UBO-QIC是与YM-254890结构相似的化合物，可抑制大鼠血小板聚集并引起血管舒张。许多试剂可用于Gαq/11下游信号转导的研究。G蛋白的作用可能代表一种新的治疗靶点。本文综述了Gαq/11在GPCR信号转导中作用的药理学和分子生物学研究方法。
G protein coupled receptors (GPCRs) are one of the major classes of cell surface receptors and are associated with a group of G proteins consisting of three subunits termed alpha, beta, and gamma. G proteins are classified into four families according to their α subunit; Gαi, Gαs, Gα12/13, and Gαq. There are several downstream pathways of Gαq of which the best known is upon activation via guanosine triphosphate (GTP), Gαq activates phospholipase Cβ, hydrolyzing phosphatidylinositol 4,5-biphosphate into diacylglycerol and inositol triphosphate and activating protein kinase C and increasing calcium efflux from the endoplasmic reticulum. Although G proteins, in particular, the Gαq/11 are central elements in GPCR signaling, their actual roles have not yet been thoroughly investigated. The lack of research of the role on Gαq/11 in cell biology is partially due to the obscure nature of the available pharmacological agents. YM-254890 is the most useful Gαq-selective inhibitor with antiplatelet, antithrombotic, and thrombolytic effects. YM-254890 inhibits Gαq signaling pathways by preventing the exchange of guanosine diphosphate for GTP. UBO-QIC is a structurally similar compound to YM-254890, which can inhibit platelet aggregation and cause vasorelaxation in rats. Many agents are available for the study of signaling downstream of Gαq/11. The role of G proteins could potentially represent a novel therapeutic target. This review will explore the range of pharmacological and molecular tools available for the study of the role of Gαq/11 in GPCR signaling.