[Heterogeneity of G protein-coupled receptor generated by post-translational mechanisms and its clinical meanings].
[Heterogeneity of G protein-coupled receptor generated by post-translational mechanisms and its clinical meanings].
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翻译后机制产生的G蛋白偶联受体的异质性及其临床意义
DOI：
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
H. Kurose
中科院分区：
文献类型：
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作者：
A. Tanoue;T. Koshimizu;G. Tsujimoto;H. Nakata;S. Hirose;Taku Fukuzawa;J. Abe;H. Kurose
G蛋白偶联受体（GPCRs）是最著名的药物靶蛋白。迄今为止，GPCR的异质性主要集中在遗传变异上。然而，据报道，GPCR的结构和功能在翻译后被几种机制修饰。RNA编辑是通过改变核苷酸的方式引入与基因组中编码的氨基酸不同的氨基酸。二聚体的形成是异质性产生的另一个例子。许多受体形成同源或异源二聚体，并获得与原始受体不同的功能。通过几种方式调节受体以调节刺激强度。受体亚型通常由受体激酶和/或第二信使调节激酶差异调节。有一种新型的受体显示出一种新的结构特征，即属于B类七跨膜受体的长氨基末端区域。这类受体的生理功能被认为在细胞间通讯中发挥作用。这种新的结构特征可能直接将GPCR连接到细胞骨架。这些产生功能和结构异质性的机制可以解释细胞如何在相同的刺激下在不同的组织或细胞中引起不同的反应。因此，产生异质性的翻译后机制在细胞对一种细胞外刺激作出反应时提供了额外的灵活性。
G protein-coupled receptors (GPCRs) are the most famous target proteins for medicinal drugs. So far, heterogeneity of GPCRs is mainly focused on genetic variation. However, it has been reported that the structure and function of GPCRs are modified by several mechanisms after translation. RNA editing introduces the amino acid different from that encoded in genome by changing the nucleotide. Dimer formation is another example of how heterogeneity is produced. Many receptors form homo- or hetero-dimers, and obtain different function from original receptors. Receptors are regulated by several means to modulate stimulation strength. Receptor subtype is often differentially regulated by receptor kinases and/or second messenger-regulated kinases. There is a new type of receptor that shows a novel structural feature, a long amino terminal region belonging to class B seven transmembrane receptors. The physiological function of this class of receptor is assumed to play a role in cell-cell communication. This novel structural feature may directly link GPCR to the cytoskeleton. These mechanisms to produce functional and structural heterogeneity may explain how cells evoke different responses in different tissues or cells upon the same stimulation. Thus, the post-translational mechanism to produce heterogeneity provides additional flexibility when cells respond to one extracellular stimulus.