Ligands and Signaling of Mas-Related G Protein-Coupled Receptor-X2 in Mast Cell Activation
Ligands and Signaling of Mas-Related G Protein-Coupled Receptor-X2 in Mast Cell Activation
复制标题
Mas 相关 G 蛋白偶联受体-X2 在肥大细胞激活中的配体和信号传导
DOI：
10.1007/112_2020_53
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Cao Yong-Xiao
中科院分区：
文献类型：
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作者：
Mi Yan-Ni;Ping Na-Na;Cao Yong-Xiao
Mas 相关 G 蛋白偶联受体-X2 (MRGPRX2) 被认为是一种激活肥大细胞 (MC) 的新型受体。 MRGPRX2 在促进 MC 依赖性宿主防御和免疫调节以及促进假性过敏药物反应、疼痛、瘙痒和炎症性疾病的发病机制中发挥双重作用。在本文中，我们讨论了MRGPRX2介导的MCs激活可能的信号通路，并对MRGPRX2在MCs激活中的激动剂和抑制剂进行了总结和分类。 MRGPRX2 是一种低亲和力和低选择性受体，使其能够与多种配体相互作用。多种 MRGPRX2 配体利用其跨膜 (TM) 结构域中的保守残基和羧基末端 Ser/Thr 残基进行配体结合和 G 蛋白偶联。这种偶联可能启动磷酸化级联反应，诱导 Ca2+ 动员，并通过 MAPK 和 NF-κB 途径引起脱颗粒并产生细胞因子和趋化因子，从而导致 MC 激活。 MC上的MRGPRX2激动剂分为肽类（包括抗菌肽、神经肽、MC脱颗粒肽、肽类激素）和非肽类（包括FDA批准的药物）。 MRGPRX2抑制剂包括非选择性GPCR抑制剂、草药提取物、小分子MRGPRX2拮抗剂和DNA适体药物。筛选和分类 MRGPRX2 配体并总结其信号通路将提高我们对 MRGPRX2 介导的 MC 生理和病理作用的理解。
Mas-related G protein-coupled receptor-X2 (MRGPRX2) is known as a novel receptor to activate mast cells (MCs). MRGPRX2 plays a dual role in promoting MC-dependent host defense and immunomodulation and contributing to the pathogenesis of pseudo-allergic drug reactions, pain, itching, and inflammatory diseases. In this article, we discuss the possible signaling pathways of MCs activation mediated by MRGPRX2 and summarize and classify agonists and inhibitors of MRGPRX2 in MCs activation. MRGPRX2 is a low-affinity and low-selectivity receptor, which allows it to interact with a diverse group of ligands. Diverse MRGPRX2 ligands utilize conserved residues in its transmembrane (TM) domains and carboxyl-terminus Ser/Thr residues to undergo ligand binding and G protein coupling. The coupling likely initiates phosphorylation cascades, induces Ca2+mobilization, and causes degranulation and generation of cytokines and chemokines via MAPK and NF-κB pathways, resulting in MCs activation. Agonists of MRGPRX2 on MCs are divided into peptides (including antimicrobial peptides, neuropeptides, MC degranulating peptides, peptide hormones) and nonpeptides (including FDA-approved drugs). Inhibitors of MRGPRX2 include non-selective GPCR inhibitors, herbal extracts, small-molecule MRGPRX2 antagonists, and DNA aptamer drugs. Screening and classifying MRGPRX2 ligands and summarizing their signaling pathways would improve our understanding of MRGPRX2-mediated physiological and pathological effects on MCs.