The novel angiotensin II type 1 receptor (AT1R)-associated protein ATRAP downregulates AT1R and ameliorates cardiomyocyte hypertrophy

• Published in: FEBS letters 2005-03, Vol.579 (7), p.1579-1586
• Main Authors: Tanaka, Yutaka, Tamura, Kouichi, Koide, Yuichi, Sakai, Masashi, Tsurumi, Yuko, Noda, Yoshihiro, Umemura, Masanari, Ishigami, Tomoaki, Uchino, Kazuaki, Kimura, Kazuo, Horiuchi, Masatsugu, Umemura, Satoshi
• Format: Article
• Language: English
• Subjects: ACE; Ad.HA-ATRAP; Ad.LacZ; Adaptor Proteins, Signal Transducing - analysis; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - physiology; adenoviral vector expressing bacterial β-galactosidase; adenoviral vector expressing hemagglutinin epitope-tagged ATRAP; Adenoviridae - genetics; Ang II; Angiotensin II; Angiotensin II type 1 receptor; angiotensin II type 1 receptor-associated protein; angiotensin II type 2 receptor; angiotensin-converting enzyme; Animals; AT1R; AT2R; ATRAP; c-Jun N-terminal kinase; C-terminal; carboxy-terminal; Cardiomegaly - genetics; Cardiomegaly - metabolism; Cardiomyocyte; Cell Size; Cells, Cultured; Down-Regulation; Downregulation; ERK; extracellular signal-regulated protein kinase; FLAG-AT1R; FLAG-tagged mouse AT1R; Genetic Vectors - genetics; HA-ATRAP; hemagglutinin epitope-tagged ATRAP; Hypertrophy; Immunoprecipitation; JNK; MAPK; Mice; mitogen-activated protein kinase; Myocytes, Cardiac - chemistry; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; p38 mitogen-activated protein kinase; p38 Mitogen-Activated Protein Kinases - metabolism; p38MAPK; PAGE; PCR; Phosphorylation; polyacrylamide gel electrophoresis; polymerase chain reaction; polyvinylidene difluoride; Protein Biosynthesis - genetics; Protein Biosynthesis - physiology; Proto-Oncogene Proteins c-fos - genetics; Proto-Oncogene Proteins c-fos - metabolism; PVDF; Receptor, Angiotensin, Type 1 - analysis; Receptor, Angiotensin, Type 1 - genetics; Receptor, Angiotensin, Type 1 - metabolism; reverse transcriptase; RNA, Messenger - analysis; RNA, Messenger - metabolism; serum response element; Signal transduction; SRE; Transcription, Genetic; Transfection
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2005.01.068

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.