TAILIEUCHUNG - Báo cáo khoa học: The impact of G-protein-coupled receptor hetero-oligomerization on function and pharmacology

Although highly controversial just a few years ago, the idea that G-pro-tein-coupled receptors (GPCRs) may undergo homo-oligomerization or hetero-oligomerization has recently gained considerable attention. The recognition that GPCRs may exhibit either dimeric or oligomeric structures is based on a number of different biochemical and biophysical approaches. | ềFEBS Journal MINIREVIEW The impact of G-protein-coupled receptor hetero-oligomerization on function and pharmacology Roberto Maggio1 Francesca Novi1 Marco Scarselli2 and Giovanni U. Corsini1 1 Department of Neurosciences University of Pisa Italy 2 NationalInstitute of Diabetes and Digestive and Kidney Diseases NIH Bethesda MD USA Keywords bivalent ligand G-protein mitogen-activated protein kinase MAPK oligomerization b-arrestin Correspondence R. Maggio Department of Neurosciences University of Pisa Via Roma 55 56100 Pisa Italy Fax 39 050 2218717 Tel 39 050 2218707 E-mail Received 16 February 2005 revised 7 April 2005 accepted 21 April 2005 Although highly controversial just a few years ago the idea that G-pro-tein-coupled receptors GPCRs may undergo homo-oligomerization or hetero-oligomerization has recently gained considerable attention. The recognition that GPCRs may exhibit either dimeric or oligomeric structures is based on a number of different biochemical and biophysical approaches. Although much effort has been spent to demonstrate the mechanism s by which GPCRs interact with each other the physiological relevance of this phenomenon remains elusive. An additional source of uncertainty stems from the realization that homo-oligomerization and hetero-oligomerization of GPCRs may affect receptor binding and activity in different ways depending on the type of interacting receptors. In this brief review the functional and pharmacological effects of the hetero-oligomerization of GPCR on binding and cell signaling are critically analyzed. doi G-protein coupled receptors GPCRs constitute the largest family of seven-transmembrane receptors. Their evolutionary success is due to their extreme versatility in binding a variety of signaling molecules such as hormones and neurotransmitters. The ubiquitous distribution in the human body along with the capacity to regulate virtually all known physiological .

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