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Functional specialization of beta-arrestin interactions revealed by proteomic analysis

Academic Article
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Overview

authors

  • Xiao, K.
  • McClatchy, D. B.
  • Shukla, A. K.
  • Zhao, Y.
  • Chen, M.
  • Shenoy, S. K.
  • Yates III, John
  • Lefkowitz, R. J.

publication date

  • July 2007

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • Beta-arrestins are cytosolic proteins that form complexes with seven-transmembrane receptors after agonist stimulation and phosphorylation by the G protein-coupled receptor kinases. They play an essential role in receptor desensitization and endocytosis, and they also serve as receptor-regulated signaling scaffolds and adaptors. Moreover, in the past decade, a growing list of protein-protein interactions of beta-arrestins pertinent to these functions has been documented. The discovery of several novel functions of beta-arrestins stimulated us to perform a global proteomics analysis of beta-arrestin-interacting proteins (interactome) as modulated by a model seven-transmembrane receptor, the angiotensin II type 1a receptor, in an attempt to assess the full range of functions of these versatile molecules. As determined by LC tandem MS, 71 proteins interacted with beta-arrestin 1, 164 interacted with beta-arrestin 2, and 102 interacted with both beta-arrestins. Some proteins bound only after agonist stimulation, whereas others dissociated. Bioinformatics analysis of the data indicates that proteins involved in cellular signaling, organization, and nucleic acid binding are the most highly represented in the beta-arrestin interactome. Surprisingly, both S-arrestin (visual arrestin) and X-arrestin (cone arrestin) were also found in heteromeric complex with beta-arrestins. The beta-arrestin interactors distribute not only in the cytoplasm, but also in the nucleus as well as other subcellular compartments. The binding of 16 randomly selected newly identified beta-arrestin partners was validated by coimmunoprecipitation assays in HEK293 cells. This study provides a comprehensive analysis of proteins that bind beta-arrestin isoforms and underscores their potentially broad regulatory roles in mammalian cellular physiology.

subject areas

  • Arrestins
  • Blotting, Western
  • Cell Communication
  • DNA
  • Humans
  • Immunoprecipitation
  • Mass Spectrometry
  • Protein Binding
  • Protein Biosynthesis
  • Protein Processing, Post-Translational
  • Proteomics
  • Signal Transduction
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Research

keywords

  • 1a receptor
  • Angiotensin II type
  • interactome
  • mass spectrometry
  • seven-transmembrane receptor
  • signal transduction
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Identity

PubMed Central ID

  • PMC1913545

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0704849104

PubMed ID

  • 17620599
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Additional Document Info

start page

  • 12011

end page

  • 12016

volume

  • 104

issue

  • 29

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