Details

Autor(en) / Beteiligte

• Wei, Huijun
• Ahn, Seungkirl
• Shenoy, Sudha K.
• Karnik, Sadashiva S.
• Hunyady, László
• Luttrell, Louis M.
• Lefkowitz, Robert J.

Titel

Independent β-Arrestin 2 and G Protein-Mediated Pathways for Angiotensin II Activation of Extracellular Signal-Regulated Kinases 1 and 2

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2003-09, Vol.100 (19), p.10782-10787

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2003

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 β-arrestin 2-GFP and activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) (maximum stimulation ≈50% of wild type). This G protein-independent activation of mitogen-activated protein kinase is abolished by depletion of cellular β-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 ≈60% of the response blocked by the PKC inhibitor (G protein dependent) and the rest of the response blocked by depletion of cellular β-arrestin 2 by small interfering RNA (β-arrestin dependent). These findings imply the existence of independent G protein- and β-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.