GPCRs are traditionally known to behave as monomers. Yet, there is increasing evidence that they form dimers and physically interact with a variety of other membrane proteins. These include other receptors as well as non-receptor membrane proteins that affect GPCR cell surface expression, binding and functional properties (Figure 139). In certain situations, this has clearly been shown to alter the pharmacological profile of the GPCR.
Many GPCRs contain sequence motifs that direct protein-protein interactions and, therefore, have the theoretical capacity to interact with a wide range of other proteins. The yeast-2 hybrid technique (Figure 140) is well suited to monitor interactions between cytoplasmic GPCR regions and proteins within the cell. For this purpose, intracellular loops and the C-terminal tails of GPCRs can be isolated and used as 'bait' for cytosolic proteins in yeast-2 hybrid-protein interaction screens.
Using this approach, a considerable range of interactions (summarized in Figure 141) has been reported. Yet the full functional and physiological significance of some of them is not completely understood. However, some appear to affect the localization, signalling specificity, and in some cases, the pharmacological profile of GPCRs.
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