Interaction of Prokineticin Receptors with Accessory Proteins

Roberta Lattanzi, R. Miele
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Abstract

G protein-coupled receptors (GPCRs) are transmembrane proteins that mediate the intracellular pathway of signals not only through heterotrimeric GTP-binding proteins (G proteins) but also through their associations with a variety of additional partner proteins. Prokineticin receptors 1 (PKR1) and 2 (PKR2) are new members of the GPCRs whose ligands are the novel chemokines prokineticin 1 (PK1) and prokineticin 2 (PK2). The multiplicity of G proteins coupled to PKRs, the ability of PKR2 to heterodimerize, the interaction of PKR2 with accessory proteins, and the existence of alternative splice isoforms of PKR2/PK2 explain the complexity of the system in the signal transduction pathway and, consequently, in the modulation of various physiological and pathological functions. Knowledge of these mechanisms provides the basis for the development of targeted drugs with therapeutic efficacy in PK-dependent diseases.
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促肾上腺皮质激素受体与辅助蛋白质的相互作用
G 蛋白偶联受体(GPCRs)是一种跨膜蛋白,它不仅通过异三聚 GTP 结合蛋白(G 蛋白),还通过与其他各种伙伴蛋白的结合来介导细胞内的信号通路。促红细胞生成素受体 1(PKR1)和 2(PKR2)是 GPCR 的新成员,其配体是新型趋化因子促红细胞生成素 1(PK1)和促红细胞生成素 2(PK2)。与 PKR 相耦合的 G 蛋白的多样性、PKR2 异源二聚体的能力、PKR2 与附属蛋白的相互作用以及 PKR2/PK2 可供选择的剪接异构体的存在,都说明了该系统在信号转导途径中的复杂性,以及因此在调节各种生理和病理功能中的复杂性。对这些机制的了解为开发对 PK 依赖性疾病有疗效的靶向药物奠定了基础。
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