Mukoyama M, Nakajima M, Horiuchi M, Sasamura H, Pratt R E, Dzau V J
Falk Cardiovascular Research Center, Stanford University School of Medicine, California 94305-5246.
J Biol Chem. 1993 Nov 25;268(33):24539-42.
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.
血管紧张素II作用于至少两种不同的受体亚型（AT1和AT2）。血管紧张素II在成体组织中的大多数已知作用归因于AT1受体。AT2受体的功能尚不清楚，但其在胎儿组织、未成熟脑、皮肤伤口和闭锁卵泡中的丰富表达提示其在生长和发育中起作用。先前的研究表明AT2受体可能不是G蛋白偶联的。在此，我们从大鼠胎儿表达文库中克隆了一个cDNA，其编码一种具有药理学特异性、组织分布和AT2受体发育模式的独特的363个氨基酸的蛋白质。它与AT1受体在序列上有34%的同源性，具有七跨膜结构域拓扑结构。对其他受体先前数据的综述表明，该受体可能属于一类独特的七跨膜受体（包括生长抑素SSTR1、多巴胺D3和卷曲蛋白Fz），尚未证明其与G蛋白偶联。该类别的所有成员均表现出胎儿期、发育和/或神经元特异性表达。第三个细胞内环中的一个保守基序将该类别与“经典”G蛋白偶联受体区分开来，可能介导新的细胞内效应。
