title: Role of (pro)renin receptor in Ang II-mediated EGF receptor transactivation.
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 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 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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Shibayama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hitomi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobori
authors.forename: Hirohito
authors.initials: H
authors.lastname: Mori
authors.forename: Kazushi
authors.initials: K
authors.lastname: Deguchi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Masaki
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Ichihara
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000378:metabolism*; D015153:Blotting, Western; D017931:DNA Primers / Q000235:genetics; D066246:ErbB Receptors / Q000378:metabolism* / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D011956:Receptors, Cell Surface / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors; D015533:Transcriptional Activation / Q000502:physiology*; D000093342:Prorenin Receptor
chemical_list: D017931:DNA Primers; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D000804:Angiotensin II; D066246:ErbB Receptors; D048052:Mitogen-Activated Protein Kinase 3; D000093342:Prorenin Receptor