Molecular mechanisms of angiotensin II receptor internalization.
Angiotensin II (AngII) initiates cellular responses by activation of type I (AT1) and type 2 (AT2) angiotensin receptors. Both AT1 and AT1 receptors have seven transmembrane structures characteristic of G protein-coupled receptors, but only the AT1 receptor undergoes rapid internalization upon agonist binding. In addition to the agonist hormone, the peptide antagonist [Sar1,Ile8]AngII can also induce internalization of the AT1a receptor expressed in mammalian cell lines, but the nonpeptide AT1 receptor blocker losartan does not internalize. AT1 receptor internalization occurs via clathrin-coated pits, but there is evidence that, in contrast to the internalization of other G protein-coupled receptors, the internalization of the AT1 receptor is independent of dynamin and beta-arrestin. Mutagenesis studies demonstrated that AT1 receptor internalization requires two regions in the cytoplasmic tail of the receptor, but it is independent of G protein activation. The dependence of AT1 receptor internalization on the presence of a serine-threonine-rich region suggests that phosphorylation of the receptor tail may regulate the internalization process. The possible role of AT1 receptor internalization in sustained signal generation has been suggested, but its relationship to nuclear AngII receptors is not completely understood.
Hunyady
L
L
Department of Physiology, Semmelweis University of Medicine, Budapest, Hungary. Hunyady@puskin.sote.hu
D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D019393:Arrestin / Q000378:metabolism; D002478:Cells, Cultured; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis; D019204:GTP-Binding Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
D019393:Arrestin; D002966:Clathrin; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D019204:GTP-Binding Proteins