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J Clin Invest. 2002 Jun;109(11):1417-27.

Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin.

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  • 1Institut National de la Santé et de la Recherche Médicale (INSERM) U489, and Association Claude Bernard, Hopital Tenon, Paris, France. genevieve.nguyen@tnn.ap-hop-paris.fr

Abstract

Renin is an aspartyl protease essential for the control of blood pressure and was long suspected to have cellular receptors. We report the expression cloning of the human renin receptor complementary DNA encoding a 350-amino acid protein with a single transmembrane domain and no homology with any known membrane protein. Transfected cells stably expressing the receptor showed renin- and prorenin-specific binding. The binding of renin induced a fourfold increase of the catalytic efficiency of angiotensinogen conversion to angiotensin I and induced an intracellular signal with phosphorylation of serine and tyrosine residues associated to an activation of MAP kinases ERK1 and ERK2. High levels of the receptor mRNA are detected in the heart, brain, placenta, and lower levels in the kidney and liver. By confocal microscopy the receptor is localized in the mesangium of glomeruli and in the subendothelium of coronary and kidney artery, associated to smooth muscle cells and colocalized with renin. The renin receptor is the first described for an aspartyl protease. This discovery emphasizes the role of the cell surface in angiotensin II generation and opens new perspectives on the tissue renin-angiotensin system and on renin effects independent of angiotensin II.

Comment in

PMID:
12045255
[PubMed - indexed for MEDLINE]
PMCID:
PMC150992
Free PMC Article

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