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Differential Kinetic and Spatial Patterns of β-Arrestin and G Protein-mediated ERK Activation by the Angiotensin II Receptor

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Ahn, Seungkirl, Shenoy, Sudha K., Wei, Huijun, Lefkowitz, Robert J.·2004·Journal of Biological Chemistry

Abstract

The seven-membrane-spanning angiotensin II type 1A receptor activates the mitogen-activated protein kinases extracellular signal-regulated kinases 1 and 2 (ERK1/2) by distinct pathways dependent on either G protein (likely G(q)/G(11)) or beta-arrestin2. Here we sought to distinguish the kinetic and spatial patterns that characterize ERK1/2 activated by these two mechanisms. We utilized beta-arrestin RNA interference, the protein kinase C inhibitor Ro-31-8425, a mutant angiotensin II receptor (DRY/AAY), and a mutant angiotensin II peptide (SII-angiotensin), which are incapable of activating G proteins, to isolate the two pathways in HEK-293 cells. G protein-dependent activation was rapid (peak <2 min), quite transient (t((1/2)) approximately 2 min), and led to nuclear translocation of the activated ERK1/2 as assessed by confocal microscopy. In contrast, beta-arrestin2-dependent activation was slower (peak 5-10 min), quite persistent with little decrement noted out to 90 min, and entirely confined to the cytoplasm. Moreover, ERK1/2 activated via beta-arrestin2 accumulated in a pool of cytoplasmic endosomal vesicles that also contained the internalized receptors and beta-arrestin. Such differential regulation of the temporal and spatial patterns of ERK1/2 activation via these two pathways strongly implies the existence of distinct physiological endpoints.

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Metadata

Authors
Ahn, S., Shenoy, S. K., Wei, H., & Lefkowitz, R. J.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2004-08
Volume
279
Issue
34
Pages
35518-35525
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2058160393
Cited by
508
References
2
FWCI
8.64
Type
journal article
Language
en
Open access
hybrid

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