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

The N-terminal Ca2+-Independent Calmodulin-Binding Site on the Inositol 1,4,5-trisphosphate Receptor Is Responsible for Calmodulin Inhibition, Even Though This Inhibition Requires Ca2+

Nael Nadif Kasri, Geert Bultynck, Jeremy Smyth, Karolina Szlufcik, Jan B. Parys, Geert Callewaert, Ludwig Missiaen, Rafael A. Fissore, Katsuhiko Mikoshiba and Humbert de Smedt
Molecular Pharmacology August 2004, 66 (2) 276-284; DOI: https://doi.org/10.1124/mol.66.2.276
Nael Nadif Kasri
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Geert Bultynck
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeremy Smyth
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Karolina Szlufcik
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jan B. Parys
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Geert Callewaert
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ludwig Missiaen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rafael A. Fissore
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katsuhiko Mikoshiba
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Humbert de Smedt
  • 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

Calmodulin (CaM) is a ubiquitous Ca2+-sensor protein that plays an important role in regulating a large number of Ca2+ channels, including the inositol 1,4,5-trisphosphate receptor (IP3R). CaM binds to the IP3R at Ca2+-dependent as well as at Ca2+-independent interaction sites. In this study, we have investigated the Ca2+-independent CaM-binding site for its role in the regulation of the Ca2+-dependent bell-shaped activation curve of the IP3R. Suramin, a polysulfonated napthylurea, displaced CaM in both the presence and the absence of Ca2+. Suramin competed with CaM for binding to different peptides representing the previously identified CaM-binding sites on IP3R1. By interacting with the N-terminal Ca2+-independent CaM-binding site, suramin mimicked the functional effect of CaM and induced an allosteric but competitive inhibition of IP3 binding. Therefore, suramin also potently inhibited IP3-induced Ca2+ release (IICR) from permeabilized cells predominantly expressing IP3R1 (L15 fibroblasts) or IP3R3 (Lvec fibroblasts), even though the IP3R3 does not contain Ca2+-dependent CaM-binding sites. Furthermore, we have found that CaM1234, a CaM mutated in its four EF hands, inhibited IICR in a Ca2+-dependent way with the same potency as CaM. We conclude that CaM inhibits IICR via the N-terminal binding site. The inhibition requires Ca2+ but CaM itself is not the Ca2+ sensor for the inhibition of the IP3R.

  • Received February 25, 2004.
  • Accepted April 18, 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.
The N-terminal Ca2+-Independent Calmodulin-Binding Site on the Inositol 1,4,5-trisphosphate Receptor Is Responsible for Calmodulin Inhibition, Even Though This Inhibition Requires Ca2+
(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

The N-terminal Ca2+-Independent Calmodulin-Binding Site on the Inositol 1,4,5-trisphosphate Receptor Is Responsible for Calmodulin Inhibition, Even Though This Inhibition Requires Ca2+

Nael Nadif Kasri, Geert Bultynck, Jeremy Smyth, Karolina Szlufcik, Jan B. Parys, Geert Callewaert, Ludwig Missiaen, Rafael A. Fissore, Katsuhiko Mikoshiba and Humbert de Smedt
Molecular Pharmacology August 1, 2004, 66 (2) 276-284; DOI: https://doi.org/10.1124/mol.66.2.276

Citation Manager Formats

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

The N-terminal Ca2+-Independent Calmodulin-Binding Site on the Inositol 1,4,5-trisphosphate Receptor Is Responsible for Calmodulin Inhibition, Even Though This Inhibition Requires Ca2+

Nael Nadif Kasri, Geert Bultynck, Jeremy Smyth, Karolina Szlufcik, Jan B. Parys, Geert Callewaert, Ludwig Missiaen, Rafael A. Fissore, Katsuhiko Mikoshiba and Humbert de Smedt
Molecular Pharmacology August 1, 2004, 66 (2) 276-284; DOI: https://doi.org/10.1124/mol.66.2.276
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
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Identification of Celecoxib targets by label-free TPP
  • Editing TOP2α Intron 19 5′ SS Circumvents Drug Resistance
  • CTS Bias
Show more Article

Similar Articles

  • 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