Article ID Journal Published Year Pages File Type
2197217 Molecular and Cellular Endocrinology 2009 9 Pages PDF
Abstract

Mutations activating the angiotensin II AT1 receptor are important to identify and characterize because they give access to the activation mechanisms of this G protein coupled receptor and help to characterize the signaling pathways and the potential pathophysiology of this receptor.The different constitutively activated mutations of the AT1 receptor are mostly localized in transmembrane domains (TM) and their characterization demonstrated that release of intramolecular constraints and movements among these TM are a necessary step for receptor activation. These mutations constitutively activate Gq linked signaling pathways, receptor internalization and maybe the G protein-independent signaling pathways. Expression of such mutations in mice is linked to hypertension and cardiovascular diseases, but such natural mutations have not been identified in human pathology.

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