Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Lung inflammatory injury and tissue repair (Jul 2023)
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI117510

Arg60 to Leu mutation of the human thromboxane A2 receptor in a dominantly inherited bleeding disorder.

T Hirata, A Kakizuka, F Ushikubi, I Fuse, M Okuma, and S Narumiya

Department of Internal Medicine, Kyoto University Faculty of Medicine, Japan.

Find articles by Hirata, T. in: JCI | PubMed | Google Scholar

Department of Internal Medicine, Kyoto University Faculty of Medicine, Japan.

Find articles by Kakizuka, A. in: JCI | PubMed | Google Scholar

Department of Internal Medicine, Kyoto University Faculty of Medicine, Japan.

Find articles by Ushikubi, F. in: JCI | PubMed | Google Scholar

Department of Internal Medicine, Kyoto University Faculty of Medicine, Japan.

Find articles by Fuse, I. in: JCI | PubMed | Google Scholar

Department of Internal Medicine, Kyoto University Faculty of Medicine, Japan.

Find articles by Okuma, M. in: JCI | PubMed | Google Scholar

Department of Internal Medicine, Kyoto University Faculty of Medicine, Japan.

Find articles by Narumiya, S. in: JCI | PubMed | Google Scholar

Published October 1, 1994 - More info

Published in Volume 94, Issue 4 on October 1, 1994
J Clin Invest. 1994;94(4):1662–1667. https://doi.org/10.1172/JCI117510.
© 1994 The American Society for Clinical Investigation
Published October 1, 1994 - Version history
View PDF
Abstract

Recent advances in molecular genetics have revealed the mechanisms underlying a variety of inherited human disorders. Among them, mutations in G protein-coupled receptors have clearly demonstrated two types of abnormalities, namely loss of function and constitutive activation of the receptors. Thromboxane A2 (TXA2) receptor is a member of the family of G protein-coupled receptors and performs an essential role in hemostasis by interacting with TXA2 to induce platelet aggregation. Here we identify a single amino acid substitution (Arg60-->Leu) in the first cytoplasmic loop of the TXA2 receptor in a dominantly inherited bleeding disorder characterized by defective platelet response to TXA2. This mutation was found exclusively in affected members of two unrelated families with the disorder. The mutant receptor expressed in Chinese hamster ovary cells showed decreased agonist-induced second messenger formation despite its normal ligand binding affinities. These results suggest that the Arg60 to Leu mutation is responsible for the disorder. Moreover, dominant inheritance of the disorder suggests the possibility that the mutation produces a dominant negative TXA2 receptor.

Images.

Browse pages

Click on an image below to see the page. View PDF of the complete article

icon of scanned page 1662
page 1662
icon of scanned page 1663
page 1663
icon of scanned page 1664
page 1664
icon of scanned page 1665
page 1665
icon of scanned page 1666
page 1666
icon of scanned page 1667
page 1667
Version history
  • Version 1 (October 1, 1994): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts