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Science 24 November 2000:
Vol. 290. no. 5496, pp. 1574 - 1577
DOI: 10.1126/science.290.5496.1574
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Reports

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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Arrestins Block G Protein-coupled Receptor-mediated Apoptosis.
C. M. Revankar, C. M. Vines, D. F. Cimino, and E. R. Prossnitz (2004)
J. Biol. Chem. 279, 24578-24584
   Abstract »    Full Text »    PDF »
Scaffold Proteins in Mammalian MAP Kinase Cascades.
K. Yoshioka (2004)
J. Biochem. 135, 657-661
   Abstract »    Full Text »    PDF »
G Protein-Coupled Receptor Internalization Signaling Is Required for Cardioprotection in Ischemic Preconditioning.
H. Tong, H. A. Rockman, W. J. Koch, C. Steenbergen, and E. Murphy (2004)
Circ. Res. 94, 1133-1141
   Abstract »    Full Text »    PDF »
The Paired Activation of the Two Components of the Muscarinic M3 Receptor Dimer Is Required for Induction of ERK1/2 Phosphorylation.
F. Novi, M. Scarselli, G. U. Corsini, and R. Maggio (2004)
J. Biol. Chem. 279, 7476-7486
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Reciprocal Regulation of Angiotensin Receptor-activated Extracellular Signal-regulated Kinases by {beta}-Arrestins 1 and 2.
S. Ahn, H. Wei, T. R. Garrison, and R. J. Lefkowitz (2004)
J. Biol. Chem. 279, 7807-7811
   Abstract »    Full Text »    PDF »
Cytoskeletal Reorganization Dependence of Signaling by the Gonadotropin-releasing Hormone Receptor.
L. Davidson, A. J. Pawson, R. P. Millar, and S. Maudsley (2004)
J. Biol. Chem. 279, 1980-1993
   Abstract »    Full Text »    PDF »
{beta}-Arrestin1 Mediates Insulin-like Growth Factor 1 (IGF-1) Activation of Phosphatidylinositol 3-Kinase (PI3K) and Anti-apoptosis.
T. J. Povsic, T. A. Kohout, and R. J. Lefkowitz (2003)
J. Biol. Chem. 278, 51334-51339
   Abstract »    Full Text »    PDF »
The Unique Amino-terminal Region of the PDE4D5 cAMP Phosphodiesterase Isoform Confers Preferential Interaction with {beta}-Arrestins.
G. B. Bolger, A. McCahill, E. Huston, Y.-F. Cheung, T. McSorley, G. S. Baillie, and M. D. Houslay (2003)
J. Biol. Chem. 278, 49230-49238
   Abstract »    Full Text »    PDF »
Neurotrophin 3 activation of TrkC induces Schwann cell migration through the c-Jun N-terminal kinase pathway.
J. Yamauchi, J. R. Chan, and E. M. Shooter (2003)
PNAS 100, 14421-14426
   Abstract »    Full Text »    PDF »
Intersectin Activates Ras but Stimulates Transcription through an Independent Pathway Involving JNK.
R. P. Mohney, M. Das, T. G. Bivona, R. Hanes, A. G. Adams, M. R. Philips, and J. P. O'Bryan (2003)
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. 23, 8334-8344
   Abstract »    Full Text »    PDF »
{beta}-Arrestin-mediated activation of MAPK by inverse agonists reveals distinct active conformations for G protein-coupled receptors.
M. Azzi, P. G. Charest, S. Angers, G. Rousseau, T. Kohout, M. Bouvier, and G. Pineyro (2003)
PNAS 100, 11406-11411
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Independent {beta}-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2.
H. Wei, S. Ahn, S. K. Shenoy, S. S. Karnik, L. Hunyady, L. M. Luttrell, and R. J. Lefkowitz (2003)
PNAS 100, 10782-10787
   Abstract »    Full Text »    PDF »
Dishevelled 2 Recruits {beta}-Arrestin 2 to Mediate Wnt5A-Stimulated Endocytosis of Frizzled 4.
W. Chen, D. ten Berge, J. Brown, S. Ahn, L. A. Hu, W. E. Miller, M. G. Caron, L. S. Barak, R. Nusse, and R. J. Lefkowitz (2003)
Science 301, 1391-1394
   Abstract »    Full Text »    PDF »
A {beta}-Arrestin-dependent Scaffold Is Associated with Prolonged MAPK Activation in Pseudopodia during Protease-activated Receptor-2-induced Chemotaxis.
L. Ge, Y. Ly, M. Hollenberg, and K. DeFea (2003)
J. Biol. Chem. 278, 34418-34426
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c-Src Is Activated by the Epidermal Growth Factor Receptor in a Pathway That Mediates JNK and ERK Activation by Gonadotropin-releasing Hormone in COS7 Cells.
S. Kraus, O. Benard, Z. Naor, and R. Seger (2003)
J. Biol. Chem. 278, 32618-32630
   Abstract »    Full Text »    PDF »
MAPK-dependent Degradation of G Protein-coupled Receptor Kinase 2.
A. Elorza, P. Penela, S. Sarnago, and F. Mayor Jr. (2003)
J. Biol. Chem. 278, 29164-29173
   Abstract »    Full Text »    PDF »
G-protein-coupled Receptor (GPCR) Kinase Phosphorylation and {beta}-Arrestin Recruitment Regulate the Constitutive Signaling Activity of the Human Cytomegalovirus US28 GPCR.
W. E. Miller, D. A. Houtz, C. D. Nelson, P. E. Kolattukudy, and R. J. Lefkowitz (2003)
J. Biol. Chem. 278, 21663-21671
   Abstract »    Full Text »    PDF »


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