イチハラ　アツヒロ   ICHIHARA Atsuhiro   市原　淳弘    所属   医学部 医学科（東京女子医科大学病院）    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Role of (pro)renin receptor in Ang II-mediated EGF receptor transactivation.
掲載誌名	正式名：Frontiers in bioscience (Elite edition) 略　 称：Front Biosci (Elite Ed) ISSNコード：1945-0508(Electronic)1945-0494(Linking)
巻・号・頁	5,pp.697-705
著者・共著者	SHIBAYAMA Yuki†, HITOMI Hirofumi, NAKANO Daisuke, KOBORI Hiroyuki, MORI Hirohito, DEGUCHI Kazushi, MASAKI Tsutomu, ICHIHARA Atsuhiro, NISHIYAMA Akira
発行年月	2013/01
概要	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 prorenin-induced 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 latepeaks 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.
文献番号	23277024