IMR Press / FBL / Volume 12 / Issue 13 / DOI: 10.2741/2429

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 as a courtesy and upon agreement with Frontiers in Bioscience.

Role of "handle" region of prorenin prosegment in the non-proteolytic activation of prorenin by binding to membrane anchored (pro)renin receptor
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1 Graduate School of Agricultural Science, Gifu University, Gifu, Japan
2 Faculty of Applied Biological Sciences, Gifu University, Gifu 501-1193, Japan
3 Division of Nephrology and Hypertension, Department of Medicine, Texas A & M University college of Medicine/ Scott & White hospital, Temple, Texas 76504, USA
4 Keio University School of Medicine, Tokyo 160-8582, Japan, USA
5 Department of Biochemistry School of Medicine, Vanderbilt University, Nashville 37235, TN, USA
Front. Biosci. (Landmark Ed) 2007, 12(13), 4810–4817;
Published: 1 September 2007

A role of the "handle" region in the prorenin prosegment sequence was investigated to demonstrate the crucial non-proteolytic activation of prorenin by binding to the recombinant (pro)renin receptor on the COS-7 cell membrane. The plasmid DNA containing either rat or human (pro)renin receptor was transfected into the COS-7 cells. The highest amount of receptor was observed on the COS-7 cell membrane after 18 h transfection. Of the total rat and human prorenin, 90% and 50% were bound to each of the respective receptors, respectively. The Kd values were 0.89 and 1.8 nM, respectively. Rat prorenin was activated non-proteolytically by the receptor. The Km was determined 1.0 µM when sheep angiotensinogen was used as the substrate. Human prorenin was also activated by the receptor. The Km was 0.71 µM. Additionally, decapeptides (10P-19P) known as "decoy" peptide and pentapeptides (11P-15P) named "handle" region peptide, were observed to inhibit the binding of both prorenins to receptors, respectively. The Ki were similar around 7 nM for both the peptides. Other two region peptides in the prosegment did not interfere the binding. These results show that the "handle" region probably plays a crucial role in prorenin binding to the receptor and in its enzymic activity by non-proteolytic activation.

COS-7 cell
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