ATRAP, novel AT1 receptor associated protein, enhances internalization of AT1 receptor and inhibits vascular smooth muscle cell growth.
We have identified a novel, membrane-located protein that interacts specifically with the carboxyl-terminal cytoplasmic domain of the AT1a receptor, which we named ATRAP (for AT1 receptor-associated protein). To further investigate the role of ATRAP in AT1 receptor function, we examined the effect of overexpression of ATRAP on angiotensin II (Ang II)-induced AT1 receptor desensitization and/or internalization, and cell proliferation in adult vascular smooth muscle cells (VSMCs). Transfection of ATRAP potentiated AT1 receptor internalization upon Ang II stimulation in these VSMCs. Moreover, we observed that AT1 receptor-induced DNA synthesis was markedly inhibited in ATRAP transfected VSMCs associated with the inhibition of the phosphorylation of signal transducers and activators of transcription (STAT) 3 and Akt. Our results suggest that ATRAP functions as a negative regulator in AT1 receptor-mediated cell proliferation in VSMCs.
Cui
T
T
Department of Medical Biochemistry, Ehime University School of Medicine, Ehime, Japan.
Nakagami
H
H
Iwai
M
M
Takeda
Y
Y
Shiuchi
T
T
Tamura
K
K
Daviet
L
L
Horiuchi
M
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000302:isolation & purification* / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C119712:Agtrap protein, mouse; D002352:Carrier Proteins; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin