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Arrestin mobilizes signaling proteins to the cytoskeleton and redirects their activity. J Mol Biol 2007 Apr 27;368(2):375-87

Date

03/16/2007

Pubmed ID

17359998

Pubmed Central ID

PMC1904837

DOI

10.1016/j.jmb.2007.02.053

Scopus ID

2-s2.0-33947607229   82 Citations

Abstract

Arrestins regulate the activity and subcellular localization of G protein-coupled receptors and other signaling molecules. Here, we demonstrate that arrestins bind microtubules (MTs) in vitro and in vivo. The MT-binding site on arrestins overlaps significantly with the receptor-binding site, but the conformations of MT-bound and receptor-bound arrestin are different. Arrestins recruit ERK1/2 and the E3 ubiquitin ligase Mdm2 to MTs in cells, similar to the arrestin-dependent mobilization of these proteins to the receptor. Arrestin-mediated sequestration of ERK to MTs reduces the level of ERK activation. In contrast, recruitment of Mdm2 to MTs by arrestin channels Mdm2 activity toward cytoskeleton-associated proteins, increasing their ubiquitination dramatically. The mobilization of signaling molecules to MTs is a novel biological function of arrestin proteins.

Author List

Hanson SM, Cleghorn WM, Francis DJ, Vishnivetskiy SA, Raman D, Song X, Nair KS, Slepak VZ, Klug CS, Gurevich VV

Author

Candice S. Klug PhD Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Arrestin
Binding Sites
COS Cells
Cell Line
Cell Survival
Cercopithecus aethiops
Dimerization
Extracellular Signal-Regulated MAP Kinases
Humans
Microtubules
Protein Binding
Protein Conformation
Protein Transport
Proto-Oncogene Proteins c-mdm2
Signal Transduction
Tubulin
jenkins-FCD Prod-411 e00897e83867fcfa48419861683711f8d99adb75