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

Side-Chain Substitutions within Angiotensin II Reveal Different Requirements for Signaling, Internalization, and Phosphorylation of Type 1A Angiotensin Receptors

Alice C. Holloway, Hongwei Qian, Luisa Pipolo, James Ziogas, Shin-ichiro Miura, Sadashiva Karnik, Bridget R. Southwell, Michael J. Lew and Walter G. Thomas
Molecular Pharmacology April 2002, 61 (4) 768-777; DOI: https://doi.org/10.1124/mol.61.4.768
Alice C. Holloway
1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hongwei Qian
1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Luisa Pipolo
1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James Ziogas
1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shin-ichiro Miura
1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sadashiva Karnik
1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bridget R. Southwell
1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael J. Lew
1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Walter G. Thomas
1 2 3 4
  • 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

Binding of the peptide hormone angiotensin II (AngII) to the type 1 (AT1A) receptor and the subsequent activation of phospholipase C-mediated signaling, involves specific determinants within the AngII peptide sequence. In contrast, the contribution of such determinants to AT1A receptor internalization, phosphorylation and activation of mitogen-activated protein kinase (MAPK) signaling is not known. In this study, the internalization of an enhanced green fluorescent protein-tagged AT1A receptor (AT1A-EGFP), in response to AngII and a series of substituted analogs, was visualized and quantified using confocal microscopy. AngII-stimulation resulted in a rapid, concentration-dependent internalization of the chimeric receptor, which was prevented by pretreatment with the nonpeptide AT1receptor antagonist EXP3174. Remarkably, AT1A receptor internalization was unaffected by substitution of AngII side chains, including single and double substitutions of Tyr4 and Phe8 that abolish phospholipase C signaling through the receptor. AngII-induced receptor phosphorylation was significantly inhibited by several substitutions at Phe8 as well as alanine replacement of Asp1. The activation of MAPK was only significantly inhibited by substitutions at position eight in the peptide and specific substitutions did not equally inhibit inositol phosphate production, receptor phosphorylation and MAPK activation. These results indicate that separate, yet overlapping, contacts made between the AngII peptide and the AT1A receptor select/induce distinct receptor conformations that preferentially affect particular receptor outcomes. The requirements for AT1A receptor internalization seem to be less stringent than receptor activation and signaling, suggesting an inherent bias toward receptor deactivation.

  • 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: 61 (4)
Molecular Pharmacology
Vol. 61, Issue 4
1 Apr 2002
  • 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.
Side-Chain Substitutions within Angiotensin II Reveal Different Requirements for Signaling, Internalization, and Phosphorylation of Type 1A Angiotensin Receptors
(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

Side-Chain Substitutions within Angiotensin II Reveal Different Requirements for Signaling, Internalization, and Phosphorylation of Type 1A Angiotensin Receptors

Alice C. Holloway, Hongwei Qian, Luisa Pipolo, James Ziogas, Shin-ichiro Miura, Sadashiva Karnik, Bridget R. Southwell, Michael J. Lew and Walter G. Thomas
Molecular Pharmacology April 1, 2002, 61 (4) 768-777; DOI: https://doi.org/10.1124/mol.61.4.768

Citation Manager Formats

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

Share
Research ArticleArticle

Side-Chain Substitutions within Angiotensin II Reveal Different Requirements for Signaling, Internalization, and Phosphorylation of Type 1A Angiotensin Receptors

Alice C. Holloway, Hongwei Qian, Luisa Pipolo, James Ziogas, Shin-ichiro Miura, Sadashiva Karnik, Bridget R. Southwell, Michael J. Lew and Walter G. Thomas
Molecular Pharmacology April 1, 2002, 61 (4) 768-777; DOI: https://doi.org/10.1124/mol.61.4.768
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

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

Related Articles

Cited By...

More in this TOC Section

  • The binding site for KCI807 in the androgen receptor
  • Fatty acid amide hydrolase in cisplatin nephrotoxicity
  • eCB Signaling System in hiPSC-Derived Neuronal Cultures
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