Phosphorylation of beta-arrestin2 regulates its function in internalization of beta(2)-adrenergic receptors

Biochemistry. 2002 Aug 27;41(34):10692-9. doi: 10.1021/bi025705n.


Beta-arrestins mediate agonist-dependent desensitization and internalization of G protein-coupled receptors. Previously, we have shown that phosphorylation of beta-arrestin1 by ERKs at Ser-412 regulates its association with clathrin and its function in promoting clathrin-mediated internalization of the receptor. In this paper we report that beta-arrestin2 is also phosphorylated, predominantly at residues Thr-383 and Ser-361. Isoproterenol stimulation of the beta(2)-adrenergic receptor promotes dephosphorylation of beta-arrestin2. Mutation of beta-arrestin2 phosphorylation sites to aspartic acid decreases the association of beta-arrestin2 with clathrin, thereby reducing its ability to promote internalization of the beta(2)-adrenergic receptor. Its ability to bind and desensitize the beta(2)-adrenergic receptor is, however, unaltered. These results suggest that, analogous to beta-arrestin1, phosphorylation/dephosphorylation of beta-arrestin2 regulates clathrin-mediated internalization of the beta(2)-adrenergic receptor. In contrast to beta-arrestin1, which is phosphorylated by ERK1 and ERK2, phosphorylation of beta-arrestin2 at Thr-383 is shown to be mediated by casein kinase II. Recently, it has been reported that phosphorylation of visual arrestin at Ser-366 prevents its binding to clathrin. Thus it appears that the function of all arrestin family members in mediating internalization of G protein-coupled receptors is regulated by distinct phosphorylation/dephosphorylation mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic beta-2 Receptor Agonists
  • Animals
  • Arrestins / genetics
  • Arrestins / metabolism*
  • COS Cells
  • Casein Kinase II
  • Cell Line
  • Clathrin / metabolism
  • Down-Regulation
  • Endocytosis
  • Humans
  • Isoproterenol / pharmacology
  • Phosphorylation / drug effects
  • Point Mutation / genetics
  • Protein Binding
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Serine / genetics
  • Serine / metabolism
  • Threonine / genetics
  • Threonine / metabolism
  • Time Factors
  • beta-Arrestins


  • Adrenergic beta-2 Receptor Agonists
  • Arrestins
  • Clathrin
  • Receptors, Adrenergic, beta-2
  • beta-Arrestins
  • Threonine
  • Serine
  • Casein Kinase II
  • Protein-Serine-Threonine Kinases
  • Isoproterenol