Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Molecular Analysis of β2-Adrenoceptor Coupling to Gs-, Gi-, and Gq-Proteins

Katharina Wenzel-Seifert and Roland Seifert
Molecular Pharmacology November 2000, 58 (5) 954-966; DOI: https://doi.org/10.1124/mol.58.5.954
Katharina Wenzel-Seifert
Howard Hughes Medical Institute, Stanford University Medical School, Stanford, California; and Department of Pharmacology and Toxicology, The University of Kansas, Lawrence, Kansas
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roland Seifert
Howard Hughes Medical Institute, Stanford University Medical School, Stanford, California; and Department of Pharmacology and Toxicology, The University of Kansas, Lawrence, Kansas
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

The β2-adrenoceptor (β2AR) couples to the G-protein Gs to activate adenylyl cyclase. Intriguingly, several studies have demonstrated that the β2AR can also interact with G-proteins of the Gi- and Gq-family. To assess the efficiency of β2AR interaction with various G-protein α-subunits (Gxα), we expressed fusion proteins of the β2AR with the long (Gsα L) and short (Gsα S) splice variants of Gsα, the Gi-proteins Giα 2 and Giα 3, and the Gq-proteins Gqα and G16α in Sf9 cells. Fusion proteins provide a rigorous approach for comparing the coupling of a given receptor to Gxα because of the defined 1:1 stoichiometry of receptor and G-protein and the efficient coupling. Here, we show that the β2AR couples to Gs-, Gi-, and Gq-proteins as assessed by ternary complex formation and ligand-regulated guanosine 5′-O-(3-thiotriphosphate) (GTPγS) binding. The combined analysis of ternary complex formation, GTPγS binding, agonist efficacies, and agonist potencies revealed substantial differences in the interaction of the β2AR with the various classes of G-proteins. Comparison of the coupling of the β2AR and formyl peptide receptor to Giα 2 revealed receptor-specific differences in the kinetics of GTPγS binding. We also detected highly efficient stimulation of GTPγS dissociation from Gsα L, but not from Gqα and G16α, by a β2AR agonist. Moreover, we show that the 1:1 stoichiometry of receptor to G-protein in fusion proteins reflects the in vivo stoichiometry of receptor/G-protein coupling more closely than was previously assumed. Collectively, our data show 1) that the β2AR couples differentially to Gs-, Gi-, and Gq-proteins, 2) that there is ligand-specific coupling of the β2AR to G-proteins, 3) that receptor-specific G-protein conformational states may exist, and 4) that nucleotide dissociation is an important mechanism for G-protein deactivation.

Footnotes

    • Received November 18, 1999.
    • Accepted July 31, 2000.
  • Send reprint requests to: Dr. Roland Seifert, Department of Pharmacology and Toxicology, The University of Kansas, 5064 Malott Hall, Lawrence, KS 66045. E-mail:rseifert{at}falcon.cc.ukans.edu

  • This work was supported by The New Faculty Award of the University of Kansas and the J.R. and Inez Jay BioMedical Research Award of The Higuchi Biosciences Center of the University of Kansas to R.S. While working in Stanford, R.S. and K.W.S. were supported by a research fellowship of the Deutsche Forschungsgemeinschaft.

  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 58 (5)
Molecular Pharmacology
Vol. 58, Issue 5
1 Nov 2000
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Molecular Analysis of β2-Adrenoceptor Coupling to Gs-, Gi-, and Gq-Proteins
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Molecular Analysis of β2-Adrenoceptor Coupling to Gs-, Gi-, and Gq-Proteins

Katharina Wenzel-Seifert and Roland Seifert
Molecular Pharmacology November 1, 2000, 58 (5) 954-966; DOI: https://doi.org/10.1124/mol.58.5.954

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Research ArticleArticle

Molecular Analysis of β2-Adrenoceptor Coupling to Gs-, Gi-, and Gq-Proteins

Katharina Wenzel-Seifert and Roland Seifert
Molecular Pharmacology November 1, 2000, 58 (5) 954-966; DOI: https://doi.org/10.1124/mol.58.5.954
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Experimental Procedures
    • Results and Discussion
    • Acknowledgments
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • 6-Methylflavone Blocks Bitterness of Tenofovir
  • Positive Allosteric Modulation of the mGlu5 Receptor
  • Correction of mutant CNGA3 channel trafficking defect
Show more Article

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2021 by the American Society for Pharmacology and Experimental Therapeutics