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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.

dc.contributor.author Wei, Huijun
dc.contributor.author Ahn, Seungkirl
dc.contributor.author Shenoy, Sudha K
dc.contributor.author Karnik, Sadashiva S
dc.contributor.author Hunyady, László
dc.contributor.author Luttrell, Louis M
dc.contributor.author Lefkowitz, Robert J
dc.coverage.spatial United States
dc.date.accessioned 2013-09-05T15:11:25Z
dc.date.issued 2003-09-16
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/12949261
dc.identifier 1834556100
dc.identifier.issn 0027-8424
dc.identifier.uri https://hdl.handle.net/10161/7797
dc.description.abstract Stimulation of a mutant angiotensin type 1A receptor (DRY/AAY) with angiotensin II (Ang II) or of a wild-type receptor with an Ang II analog ([sarcosine1,Ile4,Ile8]Ang II) fails to activate classical heterotrimeric G protein signaling but does lead to recruitment of beta-arrestin 2-GFP and activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) (maximum stimulation approximately 50% of wild type). This G protein-independent activation of mitogen-activated protein kinase is abolished by depletion of cellular beta-arrestin 2 but is unaffected by the PKC inhibitor Ro-31-8425. In parallel, stimulation of the wild-type angiotensin type 1A receptor with Ang II robustly stimulates ERK1/2 activation with approximately 60% of the response blocked by the PKC inhibitor (G protein dependent) and the rest of the response blocked by depletion of cellular beta-arrestin 2 by small interfering RNA (beta-arrestin dependent). These findings imply the existence of independent G protein- and beta-arrestin 2-mediated pathways leading to ERK1/2 activation and the existence of distinct "active" conformations of a seven-membrane-spanning receptor coupled to each.
dc.language eng
dc.publisher Proceedings of the National Academy of Sciences
dc.relation.ispartof Proc Natl Acad Sci U S A
dc.relation.isversionof 10.1073/pnas.1834556100
dc.subject Amino Acid Sequence
dc.subject Angiotensin II
dc.subject Animals
dc.subject Arrestins
dc.subject Base Sequence
dc.subject Cell Line
dc.subject DNA Primers
dc.subject Enzyme Activation
dc.subject Enzyme Inhibitors
dc.subject GTP-Binding Proteins
dc.subject Humans
dc.subject Mitogen-Activated Protein Kinase 1
dc.subject Mitogen-Activated Protein Kinase 3
dc.subject Mitogen-Activated Protein Kinases
dc.subject Molecular Sequence Data
dc.subject Rats
dc.subject beta-Arrestin 2
dc.subject beta-Arrestins
dc.title Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2.
dc.type Journal article
duke.contributor.id Ahn, Seungkirl|0120010
duke.contributor.id Shenoy, Sudha K|0232652
duke.contributor.id Lefkowitz, Robert J|0096962
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/12949261
pubs.begin-page 10782
pubs.end-page 10787
pubs.issue 19
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biochemistry
pubs.organisational-group Cell Biology
pubs.organisational-group Chemistry
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Cardiology
pubs.organisational-group Pathology
pubs.organisational-group School of Medicine
pubs.organisational-group Trinity College of Arts & Sciences
pubs.publication-status Published
pubs.volume 100


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