Adapter proteins and promoter regulation of the angiotensin AT2 receptor — implications for cardiac pathophysiology

Abstract

The angiotensin AT( 2) receptor (AT(2)R) represents an important component of the renin-angiotensin system since it is involved in the (patho) physiology of different cardiovascular and neuronal diseases. Furthermore, AT(2) receptors can partly mediate beneficial effects of angiotensin AT( 1) receptor (AT(1)R) blockers, and direct pharmacological AT( 2) receptor agonism emerges as a novel therapeutic strategy. This review discusses the constitutive and ligand-mediated activity as well as the signal transduction of the AT(2) receptor, focusing on adapter proteins which directly bind to this receptor. Direct protein-protein interaction partners of the AT(2) receptor described so far include the transcription factor promyelocytic zinc finger protein, AT(2) receptor binding protein and the AT(1) receptor. In addition, the putative crosstalk of the AT(2) receptor with the renin/ prorenin receptor (RER) via the promyelocytic zinc finger protein (PLZF) and the role of oestrogens on the regulation of the AT(2) receptor are presented. Conceiving the coupling of the AT(2) receptor to different adapter proteins with distinct and partly opposing cellular effects and the implications of its constitutive activity might help to overcome the current controversies on the (patho)physiological role of the AT(2) receptor.