Expression cloning of type 2 angiotensin II receptor reveals a unique class of seven-transmembrane receptors

• Published in: The Journal of biological chemistry Vol. 268; no. 33; pp. 24539 - 24542
• Main Authors: Mukoyama, M, Nakajima, M, Horiuchi, M, Sasamura, H, Pratt, R E, Dzau, V J
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 25.11.1993; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Cell Line; Cell Membrane - metabolism; Cell receptors; Cell structures and functions; Cloning, Molecular; DNA, Complementary; Fundamental and applied biological sciences. Psychology; GTP-Binding Proteins - metabolism; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors; Molecular and cellular biology; Molecular Sequence Data; Rats; Rats, Sprague-Dawley; Receptors, Angiotensin - classification; Receptors, Angiotensin - genetics; Receptors, Angiotensin - metabolism; RNA, Messenger - metabolism; Sequence Homology, Amino Acid; Vertebrata; Mammalia; Rat; Substrate specificity; Peptide hormone; Rodentia; Primary structure; Angiotensin II; Molecular cloning; Gene expression; Hormonal receptor
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)74498-6

Angiotensin II acts on at least two distinct receptor subtypes (AT1 and AT2). Most known effects of angiotensin II in adult tissues are attributable to the AT1 receptor. The function of AT2 receptor is undefined, but its abundant expressions in fetal tissues, immature brain, skin wound, and atretic ovarian follicles suggest a role in growth and development. Previous studies suggested that AT2 receptor may not be G protein-coupled. Here, from a rat fetus expression library, we cloned a cDNA encoding a unique 363-amino acid protein with pharmacological specificity, tissue distribution, and developmental pattern of the AT2 receptor. It is 34% identical in sequence to the AT1 receptor, sharing a seven-transmembrane domain topology. A review of prior data on other receptors suggests that this receptor may belong to a unique class of seven-transmembrane receptors (including somatostatin SSTR1, dopamine D3, and frizzled protein Fz) for which G protein coupling has not been demonstrated. All members of this class exhibit fetal and developmental and/or neuronal-specific expression. A conserved motif in the third intracellular loop, distinguishing this class from “classical” G protein-coupled receptors, may mediate novel intracellular effects.