Angiotensin II Type 1 Receptor–associated Protein

Abstract

See related article, pp 1203–1210 Most physiological actions of angiotensin (Ang) II are mediated by its binding to the Ang II type 1 receptors (AT1R). These include, but are not limited to, vasoconstriction, increased renal sodium and water reabsorption, as well as the stimulation of aldosterone release, thirst, vasopressin secretion, and cell growth. Not surprisingly, the biochemistry of the AT1R has been a subject of intense research for >30 years. These studies revealed that the cytoplasmic tail of the AT1R is an important site for several protein-to-protein interactions, phosphorylation, and thereby the regulation of receptor signaling, desensitization, and endocytosis.1 Accordingly, considerable efforts have been made to identify and to study molecules with affinity to this region; one of such molecules is the angiotensin receptor–associated protein (ATRAP). ATRAP is an 18-kDa protein that was first identified and cloned in 1999 using a yeast 2-hybrid assay.2 Successive in vitro studies showed that ATRAP lacks catalytic activity.3 Instead, ATRAP is a membrane protein with 3 predicted transmembrane domains and a cytoplasmic tail that is important for its interactions with the carboxyl terminal of the AT1R.3 ATRAP colocalizes with the AT1R mostly in intracellular compartments, it induces AT1R internalization and reduces its signaling.2,3 Thus, available data indicate that ATRAP is a negative modulator of AT1R activity. ATRAP is made by many organs, including the heart, testis, and adrenal glands. However, by far the kidneys are the site of highest expression.2 Studies using gene targeting technology have provided valuable insights into the …