Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • 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
  • Submit
  • 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
    • Special Sections
    • 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
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Identification of a Novel Site within G Protein α Subunits Important for Specificity of Receptor-G Protein Interaction

Arne Heydorn, Richard J. Ward, Rasmus Jorgensen, Mette M. Rosenkilde, Thomas M. Frimurer, Graeme Milligan and Evi Kostenis
Molecular Pharmacology August 2004, 66 (2) 250-259; DOI: https://doi.org/10.1124/mol.66.2.250
Arne Heydorn
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard J. Ward
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rasmus Jorgensen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mette M. Rosenkilde
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas M. Frimurer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Graeme Milligan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Evi Kostenis
  • 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

Several domains of G protein α subunits are implicated in the control of receptor-G protein coupling specificity. Among these are the extreme N-and C-termini, the α4/β6-loops, and the loop linking the N-terminal α-helix to the β1-strand of the ras-like domain. In this study, we illustrate that single-point mutations of a highly conserved glycine residue within the linker I region of the Gαq subunit confers upon the mutant Gαq the ability to be activated by Gαi- and Gαs -coupled receptors, as evidenced by guanosine 5′-O-(3-[35S]thio)triphosphate binding and inositol phosphate turnover assays. The mutations did not affect expression of Gαq proteins nor their ability to stimulate phospholipase Cβ. It is noteworthy that both mutant and wild-type Gαq proteins are indistinguishable in their ability to reconstitute a functional Gq-PLCβ-calcium signaling pathway when cotransfected with the Gαq-coupled neurokinin 1 or muscarinic M3 receptor into mouse embryonic fibroblasts derived from Gαq/11 knockout mice. On a three-dimensional model of the receptor-G protein complex, the highly conserved linker I region connecting the helical and the GTPase domain of the Gα protein is inaccessible to the intracellular surface of the receptors. Our data indicate that receptor-G protein coupling specificity is not exclusively governed by direct receptor-G protein interaction and that it even bypasses the requirement of the extreme C terminus of Gα, a well accepted receptor recognition domain, suggesting a novel allosteric mechanism for G protein-coupled receptor-G protein selectivity.

  • Received January 14, 2004.
  • Accepted May 11, 2004.
  • 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: 66 (2)
Molecular Pharmacology
Vol. 66, Issue 2
1 Aug 2004
  • 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.
Identification of a Novel Site within G Protein α Subunits Important for Specificity of Receptor-G Protein Interaction
(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

Identification of a Novel Site within G Protein α Subunits Important for Specificity of Receptor-G Protein Interaction

Arne Heydorn, Richard J. Ward, Rasmus Jorgensen, Mette M. Rosenkilde, Thomas M. Frimurer, Graeme Milligan and Evi Kostenis
Molecular Pharmacology August 1, 2004, 66 (2) 250-259; DOI: https://doi.org/10.1124/mol.66.2.250

Citation Manager Formats

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

Share
Research ArticleArticle

Identification of a Novel Site within G Protein α Subunits Important for Specificity of Receptor-G Protein Interaction

Arne Heydorn, Richard J. Ward, Rasmus Jorgensen, Mette M. Rosenkilde, Thomas M. Frimurer, Graeme Milligan and Evi Kostenis
Molecular Pharmacology August 1, 2004, 66 (2) 250-259; DOI: https://doi.org/10.1124/mol.66.2.250
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Analgesic Effects and Mechanisms of Licochalcones
  • Induced Fit Ligand Binding to CYP3A4
  • Englerin A Inhibits T-Type Channels
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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics