Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2.
Data(s) |
16/09/2003
|
---|---|
Formato |
10782 - 10787 |
Identificador |
http://www.ncbi.nlm.nih.gov/pubmed/12949261 1834556100 Proc Natl Acad Sci U S A, 2003, 100 (19), pp. 10782 - 10787 0027-8424 |
Relação |
Proc Natl Acad Sci U S A 10.1073/pnas.1834556100 |
Tipo |
Journal Article |
Cobertura |
United States |
Resumo |
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. |
Idioma(s) |
ENG |
Palavras-Chave | #Amino Acid Sequence #Angiotensin II #Animals #Arrestins #Base Sequence #Cell Line #DNA Primers #Enzyme Activation #Enzyme Inhibitors #GTP-Binding Proteins #Humans #Mitogen-Activated Protein Kinase 1 #Mitogen-Activated Protein Kinase 3 #Mitogen-Activated Protein Kinases #Molecular Sequence Data #Rats |