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G-protein coupled receptor signal switching:a novel fundamental function
Prof Tore Bengtsson
Physiology (Wenner-Gren Institute)
Swedish Research Council - Vetenskapsrådet (VR)
Transmission of a signal across the plasma membrane is a fundamental cellular process. G-protein coupled receptors (GPCRs) are the largest class of cell surface receptors and are thus important players in this essential task. GPCRs are also the targets for more than 50 percent of all current therapeutic agents. Adrenergic receptors (ARs) are prototypical GPCRs that are activated by the endogenous hormones noradrenaline and adrenaline and involved in the regulation of virtually every organ system in the body. To understand through which mechanisms GPCRs signal into the cell and how the signal is turned off is of high importance. We believe we have found evidence for adrenergic receptor signal switching, where adrenergic receptors first couple to “classical” second messengers, are desensitized and then as a third event switches signaling pathway. This leads to activation of a molecule (PI3K) which is normally associated with the insulin signaling pathway. Signaling switching may be a paradigmatic event which occurs for all GPCRs. In this application we want to molecularly investigate the mechanism of the adrenergic receptor signal switching to PI3K. We also want to investigate if adrenergic signal switching leads to important biological end points such as regulation of glucose uptake. The long term vision is to understand if signal switching is a fundamental process of GPCRs.
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