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- W2170824969 endingPage "167" @default.
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- W2170824969 abstract "GPCRs (G-protein-coupled receptors) are members of a family of proteins which are generally regarded as the largest group of therapeutic drug targets. Ligands of GPCRs do not usually activate all cellular signalling pathways linked to a particular seven-transmembrane receptor in a uniform manner. The fundamental idea behind this concept is that each ligand has its own ability, while interacting with the receptor, to activate different signalling pathways (or a particular set of signalling pathways) and it is this concept which is known as biased signalling. The importance of biased signalling is that it may selectively activate biological responses to favour therapeutically beneficial signalling pathways and to avoid adverse effects. There are two levels of biased signalling. First, bias can arise from the ability of GPCRs to couple to a subset of the available G-protein subtypes: Gαs, Gαq/11, Gαi/o or Gα12/13. These subtypes produce the diverse effects of GPCRs by targeting different effectors. Secondly, biased GPCRs may differentially activate G-proteins or β-arrestins. β-Arrestins are ubiquitously expressed and function to terminate or inhibit classic G-protein signalling and initiate distinct β-arrestin-mediated signalling processes. The interplay of G-protein and β-arrestin signalling largely determines the cellular consequences of the administration of GPCR-targeted drugs. In the present review, we highlight the particular functionalities of biased signalling and discuss its biological effects subsequent to GPCR activation. We consider that biased signalling is potentially allowing a choice between signalling through 'beneficial' pathways and the avoidance of 'harmful' ones." @default.
- W2170824969 created "2016-06-24" @default.
- W2170824969 creator A5000432967 @default.
- W2170824969 creator A5028069486 @default.
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- W2170824969 creator A5069732713 @default.
- W2170824969 creator A5082670286 @default.
- W2170824969 creator A5086384287 @default.
- W2170824969 date "2015-08-20" @default.
- W2170824969 modified "2023-10-16" @default.
- W2170824969 title "Biased signalling: the instinctive skill of the cell in the selection of appropriate signalling pathways" @default.
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