Signal transduction of the (pro)renin receptor as a novel therapeutic target for preventing end-organ damage.
The (pro)renin receptor ((P)RR) not only represents a novel component of the renin-angiotensin system but is also a promising novel drug target because of its crucial involvement in the pathogenesis of renal and cardiac end-organ damage. This review discusses the signal transduction of the (P)RR with its adapter protein promyelocytic zinc-finger protein, the impact of this receptor, especially on cardiovascular disease, and its putative interaction with renin inhibitors such as aliskiren. Furthermore, the increasing complexity regarding the cellular function of the (P)RR is addressed, which arises by the intimate link with proton pumps and the phosphatase PRL-1, as well as by the presence of different subcellular localizations and of a soluble isoform of the (P)RR. Finally, the rationale and strategy for the development of small-molecule antagonists of the (P)RR, called renin/prorenin receptor blockers, are presented.
Funke-Kaiser
Heiko
H
Center for Cardiovascular Research/Institute of Pharmacology, Charité-University Medicine Berlin, Berlin, Germany. heiko.funke-kaiser@charite.de
Zollmann
Frank S
FS
Schefe
Jan H
JH
Unger
Thomas
T
D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology; D006801:Humans; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000502:physiology; D000093342:Prorenin Receptor
C458319:ATP6AP2 protein, human; D011956:Receptors, Cell Surface; D025262:Vacuolar Proton-Translocating ATPases; D000093342:Prorenin Receptor