IMR Press / FBE / Volume 5 / Issue 2 / DOI: 10.2741/E650

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (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

Role of (pro)renin receptor in Ang II-mediated EGF receptor transactivation

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1 Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan
2 Department of Gastroenterology, Faculty of Medicine, Kagawa University, Kagawa, Japan
3 Department of Hypertension and Endocrinology, Tokyo Women's Medical University, Tokyo, Japan

*Author to whom correspondence should be addressed.

Academic Editor: Fumiaki Suzuki

Front. Biosci. (Elite Ed) 2013, 5(2), 697–705; https://doi.org/10.2741/E650
Published: 1 January 2013
(This article belongs to the Special Issue Handle region peptide and prorenin receptor)
Abstract

Prorenin-induced intracellular signaling pathway is not fully elucidated. We investigated whether the (pro)renin receptor mediates epidermal growth factor (EGF) receptor transactivation through angiotensin (Ang) II-dependent and -independent pathways in human embryo kidney 293 cells. Prorenin (2 nmol/L) caused biphasic phosphorylation of EGF receptor (Tyr992) and extracellular signal-regulated kinase (ERK) 1/2, peaking at 5 minutes followed by a decrease and a second peak at 60- 120 minutes, whereas EGF receptor (Tyr1068) and Src were phosphorylated at only 120 minutes. These prorenininduced phosphorylation processes were inhibited by (pro)renin receptor siRNA. Similarly, Ang II type 1 (AT1) receptor blocker (ARB) or AT1 receptor siRNA completely inhibited prorenin-induced phosphorylation of EGF receptor (Tyr1068) and Src, as well as the late peaks of EGF receptor (Tyr992) and ERK 1/2. However, early peaks of EGF receptor (Tyr992) and ERK 1/2 at 5 minutes were not effectively blocked by ARB or AT1 receptor siRNA. Incubation with prorenin significantly increased Ang II levels of cell lysate. These data indicate that the (pro)renin receptor mediates EGF receptor transactivation in both Ang II-dependent and -independent pathways.

Keywords
Pro-Renin Receptor
Prorenin
Epidermal Growth Factor
EGF receptor
Angiotensin II
Ang II
Extracellular Signal-Regulated Kinase
ERK1/2
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