β-Arrestin 2

A receptor-regulated MAPK scaffold for the activation of JNK3

P. H. McDonald, C. W. Chow, W. E. Miller, S. A. Laporte, M. E. Field, F. T. Lin, R. J. Davis, R. J. Lefkowitz

Research output: Contribution to journalArticle

627 Citations (Scopus)

Abstract

β-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 β-arrestin 2 using a yeast two-hybrid screen and by coimmunoprecipitation from mouse brain extracts or cotransfectecl 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 β-arrestin 2. Cellular transfection of β-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 β-arrestin 2 and active JNK3 to intracellular vesicles. Thus, β-arrestin 2 acts as a scaffold protein, which brings the spatial distribution and activity of this MAPK module under the control of a GPCR.

Original languageEnglish (US)
Pages (from-to)1574-1577
Number of pages4
JournalScience
Volume290
Issue number5496
StatePublished - Nov 24 2000
Externally publishedYes

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Mitogen-Activated Protein Kinases
Phosphotransferases
MAP Kinase Kinase Kinase 5
Guanine Nucleotides
MAP Kinase Kinase Kinase 4
Carrier Proteins
Arrestins
Angiotensin Type 1 Receptor
JNK Mitogen-Activated Protein Kinases
COS Cells
Transfection
Yeasts
Phosphorylation
beta-Arrestin 1
Brain
Proteins

ASJC Scopus subject areas

  • General

Cite this

McDonald, P. H., Chow, C. W., Miller, W. E., Laporte, S. A., Field, M. E., Lin, F. T., ... Lefkowitz, R. J. (2000). β-Arrestin 2: A receptor-regulated MAPK scaffold for the activation of JNK3. Science, 290(5496), 1574-1577.

β-Arrestin 2 : A receptor-regulated MAPK scaffold for the activation of JNK3. / McDonald, P. H.; Chow, C. W.; Miller, W. E.; Laporte, S. A.; Field, M. E.; Lin, F. T.; Davis, R. J.; Lefkowitz, R. J.

In: Science, Vol. 290, No. 5496, 24.11.2000, p. 1574-1577.

Research output: Contribution to journalArticle

McDonald, PH, Chow, CW, Miller, WE, Laporte, SA, Field, ME, Lin, FT, Davis, RJ & Lefkowitz, RJ 2000, 'β-Arrestin 2: A receptor-regulated MAPK scaffold for the activation of JNK3', Science, vol. 290, no. 5496, pp. 1574-1577.
McDonald PH, Chow CW, Miller WE, Laporte SA, Field ME, Lin FT et al. β-Arrestin 2: A receptor-regulated MAPK scaffold for the activation of JNK3. Science. 2000 Nov 24;290(5496):1574-1577.
McDonald, P. H. ; Chow, C. W. ; Miller, W. E. ; Laporte, S. A. ; Field, M. E. ; Lin, F. T. ; Davis, R. J. ; Lefkowitz, R. J. / β-Arrestin 2 : A receptor-regulated MAPK scaffold for the activation of JNK3. In: Science. 2000 ; Vol. 290, No. 5496. pp. 1574-1577.
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