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beta-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking.

Publication ,  Journal Article
Kohout, TA; Lin, FS; Perry, SJ; Conner, DA; Lefkowitz, RJ
Published in: Proc Natl Acad Sci U S A
February 13, 2001

The two widely coexpressed isoforms of beta-arrestin (termed beta arrestin 1 and 2) are highly similar in amino acid sequence. The beta-arrestins bind phosphorylated heptahelical receptors to desensitize and target them to clathrin-coated pits for endocytosis. To better define differences in the roles of beta-arrestin 1 and 2, we prepared mouse embryonic fibroblasts from knockout mice that lack one of the beta-arrestins (beta arr1-KO and beta arr2-KO) or both (beta arr1/2-KO), as well as their wild-type (WT) littermate controls. These cells were analyzed for their ability to support desensitization and sequestration of the beta(2)-adrenergic receptor (beta(2)-AR) and the angiotensin II type 1A receptor (AT(1A)-R). Both beta arr1-KO and beta arr2-KO cells showed similar impairment in agonist-stimulated beta(2)-AR and AT(1A)-R desensitization, when compared with their WT control cells, and the beta arr1/2-KO cells were even further impaired. Sequestration of the beta(2)-AR in the beta arr2-KO cells was compromised significantly (87% reduction), whereas in the beta arr1-KO cells it was not. Agonist-stimulated internalization of the AT(1A)-R was only slightly reduced in the beta arr1-KO but was unaffected in the beta arr2-KO cells. In the beta arr1/2-KO cells, the sequestration of both receptors was dramatically reduced. Comparison of the ability of the two beta-arrestins to sequester the beta(2)-AR revealed beta-arrestin 2 to be 100-fold more potent than beta-arrestin 1. Down-regulation of the beta(2)-AR was also prevented in the beta arr1/2-KO cells, whereas no change was observed in the single knockout cells. These findings suggest that sequestration of various heptahelical receptors is regulated differently by the two beta-arrestins, whereas both isoforms are capable of supporting receptor desensitization and down-regulation.

Duke Scholars

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

February 13, 2001

Volume

98

Issue

4

Start / End Page

1601 / 1606

Location

United States

Related Subject Headings

  • beta-Arrestins
  • beta-Arrestin 2
  • beta-Arrestin 1
  • Signal Transduction
  • Receptors, Angiotensin
  • Receptors, Adrenergic, beta-2
  • Receptor, Angiotensin, Type 1
  • Protein Isoforms
  • Phosphatidylinositols
  • Mice, Knockout
 

Citation

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Kohout, T. A., Lin, F. S., Perry, S. J., Conner, D. A., & Lefkowitz, R. J. (2001). beta-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking. Proc Natl Acad Sci U S A, 98(4), 1601–1606. https://doi.org/10.1073/pnas.98.4.1601
Kohout, T. A., F. S. Lin, S. J. Perry, D. A. Conner, and R. J. Lefkowitz. “beta-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking.Proc Natl Acad Sci U S A 98, no. 4 (February 13, 2001): 1601–6. https://doi.org/10.1073/pnas.98.4.1601.
Kohout TA, Lin FS, Perry SJ, Conner DA, Lefkowitz RJ. beta-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1601–6.
Kohout, T. A., et al. “beta-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking.Proc Natl Acad Sci U S A, vol. 98, no. 4, Feb. 2001, pp. 1601–06. Pubmed, doi:10.1073/pnas.98.4.1601.
Kohout TA, Lin FS, Perry SJ, Conner DA, Lefkowitz RJ. beta-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1601–1606.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

February 13, 2001

Volume

98

Issue

4

Start / End Page

1601 / 1606

Location

United States

Related Subject Headings

  • beta-Arrestins
  • beta-Arrestin 2
  • beta-Arrestin 1
  • Signal Transduction
  • Receptors, Angiotensin
  • Receptors, Adrenergic, beta-2
  • Receptor, Angiotensin, Type 1
  • Protein Isoforms
  • Phosphatidylinositols
  • Mice, Knockout