Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3.

Published

Journal Article

beta-Arrestins, originally discovered in the context of heterotrimeric guanine nucleotide binding protein-coupled receptor (GPCR) desensitization, also function in internalization and signaling of these receptors. We identified c-Jun amino-terminal kinase 3 (JNK3) as a binding partner of beta-arrestin 2 using a yeast two-hybrid screen and by coimmunoprecipitation from mouse brain extracts or cotransfected COS-7 cells. The upstream JNK activators apoptosis signal-regulating kinase 1 (ASK1) and mitogen-activated protein kinase (MAPK) kinase 4 were also found in complex with beta-arrestin 2. Cellular transfection of beta-arrestin 2 caused cytosolic retention of JNK3 and enhanced JNK3 phosphorylation stimulated by ASK1. Moreover, stimulation of the angiotensin II type 1A receptor activated JNK3 and triggered the colocalization of beta-arrestin 2 and active JNK3 to intracellular vesicles. Thus, beta-arrestin 2 acts as a scaffold protein, which brings the spatial distribution and activity of this MAPK module under the control of a GPCR.

Full Text

Duke Authors

Cited Authors

  • McDonald, PH; Chow, CW; Miller, WE; Laporte, SA; Field, ME; Lin, FT; Davis, RJ; Lefkowitz, RJ

Published Date

  • November 24, 2000

Published In

Volume / Issue

  • 290 / 5496

Start / End Page

  • 1574 - 1577

PubMed ID

  • 11090355

Pubmed Central ID

  • 11090355

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.290.5496.1574

Language

  • eng

Conference Location

  • United States