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N-terminal tyrosine modulation of the endocytic adaptor function of the beta-arrestins.

Publication ,  Journal Article
Marion, S; Fralish, GB; Laporte, S; Caron, MG; Barak, LS
Published in: J Biol Chem
June 29, 2007

The highly homologous beta-arrestin1 and -2 adaptor proteins play important roles in the function of G protein-coupled receptors. Either beta-arrestin variant can function as a molecular chaperone for clathrin-mediated receptor internalization. This role depends primarily upon two distinct, contiguous C-terminal beta-arrestin motifs recognizing clathrin and the beta-adaptin subunit of AP2. However, a molecular basis is lacking to explain the different endocytic efficacies of the two beta-arrestin isoforms and the observation that beta-arrestin N-terminal substitution mutants can act as dominant negative inhibitors of receptor endocytosis. Despite the near identity of the beta-arrestins throughout their N termini, sequence variability is present at a small number of residues and includes tyrosine to phenylalanine substitutions. Here we show that corresponding N-terminal (Y/F)VTL sequences in beta-arrestin1 and -2 differentially regulate mu-adaptin binding. Our results indicate that the beta-arrestin1 Tyr-54 lessens the interaction with mu-adaptin and moreover is a Src phosphorylation site. A gain of endocytic function is obtained with the beta-arrestin1 Y54F substitution, which improves both the beta-arrestin1 interaction with mu-adaptin and the ability to enhance beta2-adrenergic receptor internalization. These data indicate that beta-arrestin2 utilizes mu-adaptin as an endocytic partner, and that the inability of beta-arrestin1 to sustain a similar degree of interaction with mu-adaptin may result from coordination of Tyr-54 by neighboring residues or its modification by Src kinase. Additionally, these naturally occurring variations in beta-arrestins may also differentially regulate the composition of the signaling complexes organized on the receptor.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

June 29, 2007

Volume

282

Issue

26

Start / End Page

18937 / 18944

Location

United States

Related Subject Headings

  • src-Family Kinases
  • beta-Arrestins
  • Tyrosine
  • Transport Vesicles
  • Rats
  • Protein Structure, Tertiary
  • Phosphorylation
  • Phenylalanine
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
 

Citation

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Marion, S., Fralish, G. B., Laporte, S., Caron, M. G., & Barak, L. S. (2007). N-terminal tyrosine modulation of the endocytic adaptor function of the beta-arrestins. J Biol Chem, 282(26), 18937–18944. https://doi.org/10.1074/jbc.M700090200
Marion, Sébastien, Gregory B. Fralish, Stéphane Laporte, Marc G. Caron, and Larry S. Barak. “N-terminal tyrosine modulation of the endocytic adaptor function of the beta-arrestins.J Biol Chem 282, no. 26 (June 29, 2007): 18937–44. https://doi.org/10.1074/jbc.M700090200.
Marion S, Fralish GB, Laporte S, Caron MG, Barak LS. N-terminal tyrosine modulation of the endocytic adaptor function of the beta-arrestins. J Biol Chem. 2007 Jun 29;282(26):18937–44.
Marion, Sébastien, et al. “N-terminal tyrosine modulation of the endocytic adaptor function of the beta-arrestins.J Biol Chem, vol. 282, no. 26, June 2007, pp. 18937–44. Pubmed, doi:10.1074/jbc.M700090200.
Marion S, Fralish GB, Laporte S, Caron MG, Barak LS. N-terminal tyrosine modulation of the endocytic adaptor function of the beta-arrestins. J Biol Chem. 2007 Jun 29;282(26):18937–18944.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

June 29, 2007

Volume

282

Issue

26

Start / End Page

18937 / 18944

Location

United States

Related Subject Headings

  • src-Family Kinases
  • beta-Arrestins
  • Tyrosine
  • Transport Vesicles
  • Rats
  • Protein Structure, Tertiary
  • Phosphorylation
  • Phenylalanine
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data