β12-adrenergic receptor heterodimerization regulates β2-adrenergic receptor internalization and ERK signaling efficacy

Catherine Lavoie, Jean François Mercier, Ali Salahpour, Dhiviya Umapathy, Andreas Breit, Louis Robert Villeneuve, Wei Zhong Zhu, Rui Ping Xiao, Edward G. Lakatta, Michel Bouvier, Terence E. Hébertl

Research output: Contribution to journalArticle

Abstract

β1- and β2-adrenergic receptors (β1AR and β2AR) are co-expressed in numerous tissues where they play a central role in the responses of various organs to sympathetic stimulation. Although the two receptor subtypes share some signaling pathways, each has been shown to have specific signaling and regulatory properties. Given the recent recognition that many G protein-coupled receptors can form homo- and heterodimers, the present study was undertaken to determine whether the β1AR and β2AR can form dimers in cells and, if so, to investigate the potential functional consequences of such heterodimerization. Using co-immunoprecipitation and bioluminescence resonance energy transfer, we show that β1AR and β2AR can form heterodimers in HEK 293 cells co-expressing the two receptors. Functionally, β-adrenergic stimulated adenylyl cyclase activity was found to be identical in cells expressing β1AR, β2AR, or both receptors at similar levels, indicating that heterodimerization did not affect this signaling pathway. When considering ERK1/2 MAPK activity, a significant agonist-promoted activation was detected in β2AR- but not β1AR-expressing cells. Similarly to what was observed in cells expressing the β1AR alone, no β-adrenergic stimulated ERK1/2 phosphorylation was observed in cells co-expressing the two receptors. A similar inhibition of agonist-promoted internalization of the β2AR was observed upon co-expression of the β1AR, which by itself internalized to a lesser extent. Taken together, our data suggest that heterodimerization between β1AR and β2AR inhibits the agonist-promoted internalization of the β2AR and its ability to activate the ERK1/2 MAPK signaling pathway.

Original languageEnglish (US)
Pages (from-to)35402-35410
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number38
DOIs
StatePublished - Sep 20 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'β<sub>1</sub>/β<sub>2</sub>-adrenergic receptor heterodimerization regulates β<sub>2</sub>-adrenergic receptor internalization and ERK signaling efficacy'. Together they form a unique fingerprint.

  • Cite this

    Lavoie, C., Mercier, J. F., Salahpour, A., Umapathy, D., Breit, A., Villeneuve, L. R., Zhu, W. Z., Xiao, R. P., Lakatta, E. G., Bouvier, M., & Hébertl, T. E. (2002). β12-adrenergic receptor heterodimerization regulates β2-adrenergic receptor internalization and ERK signaling efficacy. Journal of Biological Chemistry, 277(38), 35402-35410. https://doi.org/10.1074/jbc.M204163200