IMR Press / FBL / Volume 14 / Issue 3 / DOI: 10.2741/3289

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

The angiotensin II type 2 (AT2) receptor: an enigmatic seven transmembrane receptor

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1 Molecular Endocrinology Laboratory, Baker Heart Research Institute, Prahran, Victoria 3004, Australia
2 Department of Physiology, University of Melbourne, Parkville, Victoria 3010, Australia
Academic Editor:Kevin Pfleger
Front. Biosci. (Landmark Ed) 2009, 14(3), 958–972; https://doi.org/10.2741/3289
Published: 1 January 2009
(This article belongs to the Special Issue G protein-coupled receptors)
Abstract

Angiotensin II (AngII) interacts with two receptor subtypes, AT1 and AT2, belonging to the seven transmembrane receptor superfamily. Pharmacological investigations initially suggested that AT2 receptors antagonize AT1 effects. Data from AT2 receptor transgenic and knock-out mice have not been entirely consistent with this interpretation. At the cellular level, a clear mechanistic model of AT2 transduction and signalling has yet to emerge. The AT2 receptor displays the hallmark motifs and signature residues of a G protein-coupled receptor (GPCR), but fails to demonstrate most of the classic features of GPCR signalling. In recent years, unbiased screens for AT2-interacting proteins have identified novel partner proteins involved in AT2 signalling, providing new insight into the mechanisms of AT2 action. A growing body of evidence suggests that the AT2 receptor is constitutively active (i.e. signals without AngII). This review critically evaluates controversies surrounding physiological functions and signalling mechanisms of the AT2 receptor, primarily in a cardiovascular context. Recent advances in the field are highlighted and findings challenging the concept that the AT2 receptor is a conventional angiotensin receptor are considered.

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