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Science 290 (5496): 1574-1577

Copyright © 2000 by the American Association for the Advancement of Science

beta -Arrestin 2: A Receptor-Regulated MAPK Scaffold for the Activation of JNK3

Patricia H. McDonald,1* Chi-Wing Chow,2* William E. Miller,1* Stéphane A. Laporte,3 Michael E. Field,1 Fang-Tsyr Lin,1 Roger J. Davis,2 Robert J. Lefkowitz1dagger

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.

1 Howard Hughes Medical Institute and Departments of Medicine, Cardiology, and Biochemistry, Duke University Medical Center, Box 3821, Durham, NC 27710, USA.
2 Howard Hughes Medical Institute and Program in Molecular Medicine, Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
3 Department of Cell Biology, Duke University Medical Center, Box 3287, Durham, NC 27710, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed.

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J. Biol. Chem. 278, 47038-47045
   Abstract »    Full Text »    PDF »
TRUSS, a Novel Tumor Necrosis Factor Receptor 1 Scaffolding Protein That Mediates Activation of the Transcription Factor NF-{kappa}B.
S. M. Soond, J. L. Terry, J. D. Colbert, and D. W. H. Riches (2003)
Mol. Cell. Biol.