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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.

Publication ,  Journal Article
Wei, H; Ahn, S; Shenoy, SK; Karnik, SS; Hunyady, L; Luttrell, LM; Lefkowitz, RJ
Published in: Proc Natl Acad Sci U S A
September 16, 2003

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.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

September 16, 2003

Volume

100

Issue

19

Start / End Page

10782 / 10787

Location

United States

Related Subject Headings

  • beta-Arrestins
  • beta-Arrestin 2
  • Rats
  • Molecular Sequence Data
  • Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase 1
  • Humans
  • GTP-Binding Proteins
  • Enzyme Inhibitors
 

Citation

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Wei, H., Ahn, S., Shenoy, S. K., Karnik, S. S., Hunyady, L., Luttrell, L. M., & Lefkowitz, R. J. (2003). Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2. Proc Natl Acad Sci U S A, 100(19), 10782–10787. https://doi.org/10.1073/pnas.1834556100
Wei, Huijun, Seungkirl Ahn, Sudha K. Shenoy, Sadashiva S. Karnik, László Hunyady, Louis M. Luttrell, and Robert J. Lefkowitz. “Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2.Proc Natl Acad Sci U S A 100, no. 19 (September 16, 2003): 10782–87. https://doi.org/10.1073/pnas.1834556100.
Wei H, Ahn S, Shenoy SK, Karnik SS, Hunyady L, Luttrell LM, et al. Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2. Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10782–7.
Wei, Huijun, et al. “Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2.Proc Natl Acad Sci U S A, vol. 100, no. 19, Sept. 2003, pp. 10782–87. Pubmed, doi:10.1073/pnas.1834556100.
Wei H, Ahn S, Shenoy SK, Karnik SS, Hunyady L, Luttrell LM, Lefkowitz RJ. Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2. Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10782–10787.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

September 16, 2003

Volume

100

Issue

19

Start / End Page

10782 / 10787

Location

United States

Related Subject Headings

  • beta-Arrestins
  • beta-Arrestin 2
  • Rats
  • Molecular Sequence Data
  • Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase 1
  • Humans
  • GTP-Binding Proteins
  • Enzyme Inhibitors