Reciprocal Regulation of Angiotensin Receptor-activated Extracellular Signal-regulated Kinases by β-Arrestins 1 and 2

Seungkirl Ahn, Huijun Wei, Tiffany Runyan Garrison, Robert J. Lefkowitz

Research output: Contribution to journalArticle

Abstract

β-Arrestin2 not only plays essential roles in seven membrane-spanning receptor desensitization and internalization but also functions as a signal transducer in mitogen-activated protein kinase cascades. Here we show that the angiotensin II type 1A receptor-mediated activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in HEK-293 cells is increased when the cellular level of β-arrestinl is down-regulated by RNA interference but is decreased or eliminated when the cellular level of β-arrestin2 is diminished. Such reciprocal effects of down-regulated levels of β-arrestins 1 and 2 are primarily due to differences in the ability of the two forms of β-arrestins to directly mediate ERK activation. These results are the first to demonstrate reciprocal activity of β-arrestin isoforms on a signaling pathway and suggest that physiological levels of β-arrestin1 may act as "dominant-negative" inhibitors of β -arrestin2-mediated ERK activation.

Original languageEnglish (US)
Pages (from-to)7807-7811
Number of pages5
JournalJournal of Biological Chemistry
Volume279
Issue number9
DOIs
StatePublished - Feb 27 2004
Externally publishedYes

Fingerprint

Arrestins
Arrestin
Angiotensin Type 1 Receptor
Angiotensin Receptors
Mitogen-Activated Protein Kinase 3
HEK293 Cells
Mitogen-Activated Protein Kinase 1
Extracellular Signal-Regulated MAP Kinases
RNA Interference
Mitogen-Activated Protein Kinases
Transducers
Protein Isoforms
Chemical activation
Membranes
RNA
beta-Arrestin 1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Reciprocal Regulation of Angiotensin Receptor-activated Extracellular Signal-regulated Kinases by β-Arrestins 1 and 2. / Ahn, Seungkirl; Wei, Huijun; Garrison, Tiffany Runyan; Lefkowitz, Robert J.

In: Journal of Biological Chemistry, Vol. 279, No. 9, 27.02.2004, p. 7807-7811.

Research output: Contribution to journalArticle

Ahn, Seungkirl ; Wei, Huijun ; Garrison, Tiffany Runyan ; Lefkowitz, Robert J. / Reciprocal Regulation of Angiotensin Receptor-activated Extracellular Signal-regulated Kinases by β-Arrestins 1 and 2. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 9. pp. 7807-7811.
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