Association of β-arrestin 1 with the type 1A angiotensin II receptor involves phosphorylation of the receptor carboxyl terminus and correlates with receptor internalization

Qian, HW, Pipolo, L and Thomas, WG (2001) Association of β-arrestin 1 with the type 1A angiotensin II receptor involves phosphorylation of the receptor carboxyl terminus and correlates with receptor internalization. Molecular Endocrinology, 15 10: 1706-1719. doi:10.1210/me.15.10.1706


Author Qian, HW
Pipolo, L
Thomas, WG
Title Association of β-arrestin 1 with the type 1A angiotensin II receptor involves phosphorylation of the receptor carboxyl terminus and correlates with receptor internalization
Journal name Molecular Endocrinology   Check publisher's open access policy
ISSN 0888-8809
Publication date 2001-01-01
Year available 2001
Sub-type Article (original research)
DOI 10.1210/me.15.10.1706
Open Access Status Not yet assessed
Volume 15
Issue 10
Start page 1706
End page 1719
Total pages 14
Place of publication BETHESDA
Publisher ENDOCRINE SOC
Language eng
Subject 1312 Molecular Biology
2712 Endocrinology, Diabetes and Metabolism
Abstract Arrestins bind to phosphorylated G protein-coupled receptors and participate in receptor desensitization and endocytosis. Although arrestins traffic with activated type 1 (AT(1A)) angiotensin II (AngII) receptors, the contribution of arrestins to AT1A receptor internalization is controversial, and the physical association of arrestins with the AT1A receptor has not been established. In this study, by coimmunoprecipitating AT(1A) receptors and beta -arrestin 1, we provide direct evidence for an association between arrestins and the AT1A receptor that was agonist- and time-dependent and contingent upon the level of beta -arrestin I expression. Serial truncation of the receptor carboxyl terminus resulted in a graded loss of ig-arrestin 1 association, which correlated with decreases in receptor phosphorylation. Truncation of the AT1A receptor to lysine(325) prevented Angll-induced phosphorylation and beta -arrestin I association as well as markedly inhibiting receptor internalization, indicating a close correlation between these receptor parameters. Angll-induced association was also dramatically reduced in a phosphorylation- and internalization-impaired receptor mutant in which four serine and threonine residues in the central portion of the AT(1A) receptor carboxyl terminus (Thr(332), Ser(335), Thr(338), Ser(338)) were substituted with alanine. In contrast, substitutions in another serine/threonine-rich region (Ser(346), Ser(347), Ser(348)) and at three PKC phosphorylation sites (Ser(331), Ser(338), Ser(348)) had no effect on Angll-induced beta -arrestin I association or receptor internalization. While AT(1A) receptor internalization could be inhibited by a dominant-negative beta -arrestin 1 mutant (beta arr1(319-418)), treatment with hyperosmotic sucrose to inhibit internalization did not abrogate the differences in arrestin association observed between the wild-type and mutant receptors, indicating that arrestin binding precedes, and is not dependent upon, receptor internalization. Interestingly, a substituted analog of Angll, [Sar(1)Ile(4)Ile(8)]-Angll, which promotes robust phosphorylation of the receptor but does not activate receptor signaling, stimulated strong beta -arrestin 1 association with the full-length AT(1A) receptor. These results identify the central portion of the AT(1A) receptor carboxyl terminus as the important determinant for beta -arrestin I binding and internalization and indicate that AT(1A) receptor phosphorylation is crucial for beta -arrestin docking.
Keyword Endocrinology & Metabolism
Endocrinology & Metabolism
ENDOCRINOLOGY & METABOLISM
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import - Archived
 
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