The novel angiotensin II type 1 receptor (AT1R)-associated protein ATRAP downregulates AT1R and ameliorates cardiomyocyte hypertrophy.
Activation of angiotensin II (Ang II) type 1 receptor (AT1R) signaling is reported to play an important role in cardiac hypertrophy. We previously cloned a novel molecule interacting with the AT1R, which we named ATRAP (for Ang II type 1 receptor-associated protein). Here, we report that overexpression of ATRAP significantly decreases the number of AT1R on the surface of cardiomyocytes, and also decreases the degree of p38 mitogen-activated protein kinase phosphorylation, the activity of the c-fos promoter and protein synthesis upon Ang II treatment. These results indicate that ATRAP significantly promotes downregulation of the AT1R and further attenuates certain Ang II-mediated hypertrophic responses in cardiomyocytes.
Tanaka
Yutaka
Y
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Tamura
Kouichi
K
Koide
Yuichi
Y
Sakai
Masashi
M
Tsurumi
Yuko
Y
Noda
Yoshihiro
Y
Umemura
Masanari
M
Ishigami
Tomoaki
T
Uchino
Kazuaki
K
Kimura
Kazuo
K
Horiuchi
Masatsugu
M
Umemura
Satoshi
S
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism; D048429:Cell Size; D002478:Cells, Cultured; D015536:Down-Regulation; D005822:Genetic Vectors / Q000235:genetics; D006984:Hypertrophy; D047468:Immunoprecipitation; D051379:Mice; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000235:genetics / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C119712:Agtrap protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D048051:p38 Mitogen-Activated Protein Kinases