Mapping of G protein coupling sites of the angiotensin II type 1 receptor

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 25; no. 4; pp. 726 - 730
• Main Authors: SHIRAI, H, TAKAHASHI, K, KATADA, T, INAGAMI, T
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Lippincott 01.04.1995; Hagerstown, MD American Heart Association, Inc
• Subjects: Amino Acid Sequence; Animals; Apud cells. Peptide and protein hormones. Growth factors; Binding Sites; Biological and medical sciences; Chromosome Mapping; Fundamental and applied biological sciences. Psychology; GTP-Binding Proteins - metabolism; Guanosine 5'-O-(3-Thiotriphosphate) - metabolism; Molecular Sequence Data; Peptide Fragments - pharmacology; Rats; Receptors, Angiotensin - chemistry; Receptors, Angiotensin - genetics; Receptors, Angiotensin - metabolism; Vertebrates: endocrinology; Cartography; Renin angiotensin system; Vertebrata; Mammalia; Rat; Animal; Coupling site; Peptide hormone; Rodentia; Angiotensin II; G protein; Biological receptor
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.25.4.726

Angiotensin II type 1 (AT1) receptors have been identified in a wide variety of tissues, including the kidney, liver, adrenal gland, cardiovascular system, and brain. AT1 receptors also mediate complex signaling mechanisms that elicit a diversity of specific physiological effects. The rat AT1A receptor has seven transmembrane domains and couples with three distinct G proteins: Gq, Gi, and Go. But it is unknown which domains of AT1A couple with and activate each type of G protein. To identify the domains responsible for the activation of various types of G protein, we studied the effect of five different synthetic peptides representing different domains of cytosolic segments of the rat AT1A receptor on the binding of the 35S-labeled stable analogue of GTP, GTP gamma S. Peptides P-3, which is located in the N-terminal region of the putative third intracellular loop of AT1A (residues 216 through 230), and P-5 (residues 306 through 320), corresponding to the N-terminal region of the C-terminal tail, were found to activate purified Gi1, Gi2, and Go proteins. These results indicate that not only the third cytosolic loop but also the C-terminal cytosolic domain of AT1A is important for Gi1, Gi2, and Go protein coupling and activation.