Seven transmembrane receptors: something old, something new
Seven transmembrane receptors: something old, something new
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DOI：
10.1111/j.1365-201x.2007.01693.x
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发表时间：
2007-05-01
影响因子：
6.3
通讯作者：
Lefkowitz, R. J.
中科院分区：
文献类型：
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作者：
Lefkowitz, R. J.
激素、神经递质、药物、感觉刺激和许多其他因子的受体是细胞代谢和活动的门户。它们调节着哺乳动物几乎所有的生理过程。然而，就在40年前，它们的存在还是个问题。一类受体，即与G蛋白偶联的受体（也称为GPCRs或7个跨膜受体）构成了迄今为止最大的一类受体（约为7种）。1000)，是临床用药最重要的靶点。在这里，我提供了一个非常个人的研究回顾在过去的35年，最终导致了肾上腺素能受体的鉴定，纯化，重组和克隆；发现它们与7种跨膜视觉光受体视紫红质同源性，并认识到G蛋白偶联受体存在一个大的基因家族；G蛋白偶联受体激酶和β -阻滞蛋白介导的受体脱敏和信号转导的分子机制；受体的结构，信号传导和调节机制在大受体超家族中都是高度保守的。
Receptors for hormones, neurotransmitters, drugs, sensory stimuli and many other agents represent the gateway to cellular metabolism and activity. They regulate virtually all physiological processes in mammals. Yet as recently as 40 years ago their very existence was still in question. One class of receptors, those coupled to G proteins (also known as GPCRs or seven transmembrane receptors) comprise by far the largest group (approx. 1000), and are the most important target of clinically used drugs. Here I provide a very personal retrospective of research over the past 35 years which ultimately led to the identification, purification, reconstitution and cloning of the adrenergic receptors; the discovery of their homology with the seven transmembrane spanning visual light receptor rhodopsin and the realization that there was a large gene family of G protein coupled receptors; the elucidation of the molecular mechanisms of receptor desensitization and signalling through G protein-coupled receptor kinases and beta-arrestins; and the appreciation that the structure, signalling, and regulatory mechanisms of the receptors are all highly conserved across the large receptor superfamily.