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.