Heterogeneity of G protein-coupled receptor generated by post-translational mechanisms and its clinical meanings
| Autor: | Jumpei Abe, Taku Fukuzawa, Hitoshi Kurose, Shigehisa Hirose, Taka-aki Koshimizu, Hiroyasu Nakata, Gozoh Tsujimoto, Akito Tanoue |
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| Rok vydání: | 2004 |
| Předmět: |
Pharmacology
chemistry.chemical_classification Chemistry Kinase Receptors Purinergic Genetic Variation Stimulation Stimulus (physiology) Receptor Endothelin B Molecular biology Receptors G-Protein-Coupled Cell biology Amino acid RNA editing Animals Humans RNA Editing Receptor Cytoskeleton Dimerization Protein Processing Post-Translational G protein-coupled receptor |
| Zdroj: | Folia Pharmacologica Japonica. 124:235-243 |
| ISSN: | 1347-8397 0015-5691 |
| DOI: | 10.1254/fpj.124.235 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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