The role of angiotensin AT1 receptor-associated protein in renin-angiotensin system regulation and function.
We cloned a novel molecule, AT1 receptor-associated protein (ATRAP), which is expressed in many tissues but specifically interacts with the AT1 receptor carboxyl-terminal. In the kidney, ATRAP was broadly distributed along the renal tubules; salt intake modulated its expression. In cardiovascular cells, angiotensin II (Ang II) stimulation made ATRAP co-localized with AT1 receptor in cytoplasm; ATRAP overexpression decreased cell surface AT1 receptor. In downstream signaling pathways, ATRAP suppressed Ang II-induced phosphorylation of mitogen-activated protein kinase, activation of c-fos gene transcription, and enhancement of amino acid or bromodeoxyuridine incorporation in cardiovascular cells. Thus, cardiovascular ATRAP may promote AT1 receptor internalization and attenuate Ang II-mediated cardiovascular remodeling. We would expect ATRAP to become a new therapeutic target molecule to treat and prevent cardiovascular remodeling in hypertension.
Tamura
Kouichi
K
Department of Cardiorenal Medicine, Yokohama City University School of Medicine, 3-9 Fukuura, Yokohama, Japan. tamukou@med.yokohama-cu.ac.jp
Tanaka
Yutaka
Y
Tsurumi
Yuko
Y
Azuma
Koichi
K
Shigenaga
Atsu-ichiro
A
Wakui
Hiromichi
H
Masuda
Shin-Ichiro
S
Matsuda
Miyuki
M
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001794:Blood Pressure; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D012084:Renin-Angiotensin System; D015398:Signal Transduction; D020257:Ventricular Remodeling
D048868:Adaptor Proteins, Signal Transducing; D044140:Receptor, Angiotensin, Type 1