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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:15.)
© 2005 American Heart Association, Inc.

Editorials

Beyond the G Protein

The Saga of the Type 2 Angiotensin II Receptor

E.J. Landon; T. Inagami

From the Departments of Pharmacology (E.J.L.) and Biochemistry (T.I.), Vanderbilt University School of Medicine, Nashville, Tenn.

Correspondence to Tadashi Inagami, Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37205. E-mail tadashi.inagami@vanderbilt.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Studies of the large families of seven transmembrane receptors have focused on their signal transduction pathways initiated by their interaction with GTP activated proteins. Angiotensin II (Ang II) mediates most of its well known cardiovascular effects in conventional manner through its type 1 (AT₁) receptor acting on heterotrimeric G proteins. The affinity of the type 2 (AT₂) receptor specific for the G protein Gi fails in large part to explain its functional activity. It has generally opposing effects to AT₁. Although it is abundant in the fetus, its distribution is limited in the adult but is induced again under pathological conditions. Some of its important modulator signaling involves direct activation of the tyrosine phosphatase SHP-1 independent of heterotrimeric G protein signaling.^1–4 In addition it is atypical in its general failure, unlike AT₁, to quickly desensitize and downregulate with ligand binding. The following overview looks at some AT₂ functions and responses that are not mediated by an interaction with heterotrimeric G proteins. Recent articles reveal a new regulatory mechanism of AT₂ signaling.

See page 57

Heterotrimeric G proteins and arrestins interact specifically and in primary fashion with the intracellular loop 3 of 7 transmembrane receptors. Interaction of the receptors with adapter and scaffolding proteins is important for their cellular sorting and targeting to the cell membrane. The C-terminal tail of the 7 transmembrane receptors has the primary binding sites for these adaptor and scaffolding proteins.^5–8

Yeast-two-hybrid screening has been frequently used to identify potential binding proteins . . . [Full Text of this Article]

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