Association of  -Arrestin 1 with the Type 1A Angiotensin II Receptor Involves Phosphorylation of the Receptor Carboxyl Terminus and Correlates with Receptor Internalization

2001 ◽  
Vol 15 (10) ◽  
pp. 1706-1719 ◽  
Author(s):  
H. Qian
Keyword(s):  
Angiotensin Ii ◽  
Receptor Internalization ◽  
Carboxyl Terminus ◽  
Angiotensin Ii Receptor

scholarly journals Association of β-Arrestin 1 with the Type 1A Angiotensin II Receptor Involves Phosphorylation of the Receptor Carboxyl Terminus and Correlates with Receptor Internalization

2001 ◽  
Vol 15 (10) ◽  
pp. 1706-1719
Author(s):  
Hongwei Qian ◽  
Luisa Pipolo ◽  
Walter G. Thomas
Keyword(s):  
Angiotensin Ii ◽  
Close Correlation ◽  
Dominant Negative ◽  
Receptor Internalization ◽  
Central Portion ◽  
Carboxyl Terminus ◽  
Angiotensin Ii Receptor ◽  
Receptor Phosphorylation ◽  
At1a Receptor ◽  
Mutant Receptors

Abstract Arrestins bind to phosphorylated G protein-coupled receptors and participate in receptor desensitization and endocytosis. Although arrestins traffic with activated type 1 (AT1A) 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 AT1A receptors and β-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 ofβ -arrestin 1 expression. Serial truncation of the receptor carboxyl terminus resulted in a graded loss of β-arrestin 1 association, which correlated with decreases in receptor phosphorylation. Truncation of the AT1A receptor to lysine325 prevented AngII-induced phosphorylation and β-arrestin 1 association as well as markedly inhibiting receptor internalization, indicating a close correlation between these receptor parameters. AngII-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 AT1A receptor carboxyl terminus (Thr332, Ser335, Thr336, Ser338) were substituted with alanine. In contrast, substitutions in another serine/threonine-rich region (Ser346, Ser347, Ser348) and at three PKC phosphorylation sites (Ser331, Ser338, Ser348) had no effect on AngII-inducedβ -arrestin 1 association or receptor internalization. While AT1A receptor internalization could be inhibited by a dominant-negative β-arrestin 1 mutant (βarr1319–418), 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 AngII,[ Sar1Ile4Ile8]-AngII, which promotes robust phosphorylation of the receptor but does not activate receptor signaling, stimulated strong β-arrestin 1 association with the full-length AT1A receptor. These results identify the central portion of the AT1A receptor carboxyl terminus as the important determinant for β-arrestin 1 binding and internalization and indicate that AT1A receptor phosphorylation is crucial for β-arrestin docking.

Angiotensin II receptor internalization and signaling in isolated rat hepatocytes

1999 ◽  
Vol 57 (10) ◽  
pp. 1125-1131 ◽  
Author(s):  
Eugenio Jiménez ◽  
Maria C Caro ◽  
Santo Marsigliante ◽  
Mercedes Montiel
Keyword(s):  
Angiotensin Ii ◽  
Rat Hepatocytes ◽  
Receptor Internalization ◽  
Angiotensin Ii Receptor ◽  
Isolated Rat Hepatocytes ◽  
Isolated Rat

Electrostatic and Hydrophobic Forces Tether the Proximal Region of the Angiotensin II Receptor (AT1A) Carboxyl Terminus to Anionic Lipids†

Biochemistry ◽  
2002 ◽  
Vol 41 (24) ◽  
pp. 7830-7840 ◽  
Author(s):  
Henriette Mozsolits ◽  
Sharon Unabia ◽  
Ariani Ahmad ◽  
Craig J. Morton ◽  
Walter G. Thomas ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Proximal Region ◽  
Carboxyl Terminus ◽  
Angiotensin Ii Receptor ◽  
Anionic Lipids

scholarly journals Divergent conformational requirements for angiotensin II receptor internalization and signaling

1994 ◽  
Vol 46 (6) ◽  
pp. 1496-1498 ◽  
Author(s):  
László Hunyady ◽  
Ying Tian ◽  
Kathryn Sandberg ◽  
Tamás Balla ◽  
Kevin J. Catt
Keyword(s):  
Angiotensin Ii ◽  
Receptor Internalization ◽  
Angiotensin Ii Receptor
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