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- Title
Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3.
- Authors
McDonald, P H; Chow, C W; Miller, W E; Laporte, S A; Field, M E; Lin, F T; Davis, R J; Lefkowitz, R J
- Abstract
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.
- Publication
Science (New York, N.Y.), 2000, Vol 290, Issue 5496, p1574
- ISSN
0036-8075
- Publication type
Journal Article
- DOI
10.1126/science.290.5496.1574