Angiotensin II type 1 receptor–associated protein is an endogenous inhibitor of angiotensin II type 1 receptor action in cardiac hypertrophy: role in check and balance
Z Zhang, VJ Dzau - Hypertension, 2010 - Am Heart Assoc
Z Zhang, VJ Dzau
Hypertension, 2010•Am Heart AssocAngiotensin II (Ang II) type 1 (AT1) receptor is the primary effector of the renin-angiotensin
system and mediates many key physiological and pathological actions of Ang II through a
complex orchestration of intracellular signaling molecules. As a G protein–coupled receptor,
AT1 receptor activation induces the canonical Gq protein–dependent inositol phosphate
turnover and intracellular calcium release pathway, as well as receptor phosphorylation by
G protein–coupled receptor kinases and the recruitment of ß-arrestin as a G protein …
system and mediates many key physiological and pathological actions of Ang II through a
complex orchestration of intracellular signaling molecules. As a G protein–coupled receptor,
AT1 receptor activation induces the canonical Gq protein–dependent inositol phosphate
turnover and intracellular calcium release pathway, as well as receptor phosphorylation by
G protein–coupled receptor kinases and the recruitment of ß-arrestin as a G protein …
Angiotensin II (Ang II) type 1 (AT1) receptor is the primary effector of the renin-angiotensin system and mediates many key physiological and pathological actions of Ang II through a complex orchestration of intracellular signaling molecules. As a G protein–coupled receptor, AT1 receptor activation induces the canonical Gq protein–dependent inositol phosphate turnover and intracellular calcium release pathway, as well as receptor phosphorylation by G protein–coupled receptor kinases and the recruitment of ß-arrestin as a G protein–independent pathway to mediate the cellular effects of Ang II. 1 Recent investigations have highlighted the importance of the AT1 receptor carboxyl-terminal domain that binds to a variety of intracellular proteins, such as G protein–coupled receptor kinases and ß-arrestin, and plays a pivotal role on receptor internalization, desensitization, phosphorylation, and coupling to G proteins. 1 A relatively new and potentially important player in this orchestra is the AT1 receptor–associated protein (ATRAP) that interacts with the carboxyl-terminal domain of the AT1 receptor. ATRAP was first identified and isolated by yeast 2-hybrid screening from the mouse kidney cDNA library in the Dzau laboratory. 2
ATRAP is a relatively small 18-kDa protein with 1 potential N-glycosylation site, 1 potential phosphorylation site for protein kinase C, 1 potential phosphorylation site for casein kinase II, and 3 hydrophobic domains for potential transmembrane binding. 2, 3 ATRAP localizes in intracellular trafficking vesicles and plasma membrane, including endoplasmic reticulum, Golgi, and endocytic vesicles. 3 ATRAP interacts selectively with the carboxyl-terminal domain of the AT1 receptor but not with those of Ang II type 2, m3 muscarinic acetylcholine, bradykinin B2, endothelin B, and ß2-adrenergic receptors. 2 ATRAP enhances AT1 receptor desensitization and internalization. 2–4 The key question about ATRAP is its function. Tamura’s laboratory showed that, in vascular smooth muscle cells in vitro, ATRAP colocalized with the AT1 receptor, promoted
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