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
Journal of Pharmacology and Experimental Therapeutics
  • 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
Journal of Pharmacology and Experimental Therapeutics

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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleCELLULAR AND MOLECULAR

Involvement of Protein Kinase C-ε in Signal Transduction of Thrombopoietin in Enhancement of Interleukin-3-Dependent Proliferation of Primitive Hematopoietic Progenitors

Noriyuki Shiroshita, Manabu Musashi, Keisuke Sakurada, Kazuhiro Kimura, Yuzo Tsuda, Shuichi Ota, Hiroshi Iwasaki, Tamotsu Miyazaki, Takashi Kato, Hiroshi Miyazaki, Akihiro Shimosaka and Masahiro Asaka
Journal of Pharmacology and Experimental Therapeutics June 2001, 297 (3) 868-875;
Noriyuki Shiroshita
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Manabu Musashi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Keisuke Sakurada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kazuhiro Kimura
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuzo Tsuda
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shuichi Ota
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroshi Iwasaki
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tamotsu Miyazaki
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takashi Kato
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroshi Miyazaki
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Akihiro Shimosaka
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masahiro Asaka
  • 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

We studied the effect of thrombopoietin (TPO) on interleukin-3 (IL-3)-dependent bone marrow cell colony formation of mice to clarify the role of protein kinase C (PKC) in the signal transduction of TPO for the proliferation of primitive hematopoietic progenitors. TPO alone hardly yielded colonies. However, TPO in combination with IL-3 increased colony numbers synergistically from 2- to 4-fold, compared with those supported by IL-3 alone. Serial observation of colony development showed that TPO may hasten the appearance of colonies by shortening the dormant period (G0) of primitive progenitors. Immunocytochemical studies on PKC isoforms in progenitor cells stimulated with TPO have revealed that the expression pattern of PKC-ε is changed, but not that of PKC-α, -β, -γ, -δ, or -ζ. Selective PKC inhibitors, such as calphostin C and GF 109203X, and PKC-ε-specific translocation inhibitor peptide abrogated the enhancing effect of TPO on IL-3-dependent colony formation and the changes in the intracellular expression pattern of PKC-ε. These data taken together suggest that TPO has a direct effect on primitive progenitors and enhances IL-3-dependent colony formation, at least partly through the activation of PKC-ε.

Footnotes

  • Send reprint requests to: Dr. Manabu Musashi, Health Administration Center, Hokkaido University, Kita-8, Nishi-5, Kita-ku, Sapporo 060-0808, Japan. E-mail: musashim{at}med.hokudai.ac.jp

  • This work was supported in part by a grant-in-aid from the Ministry of Education, Science, and Culture of Japan (No. 04671504), by a special grant-in-aid for the Promotion of Education and Science at Hokkaido University from the same source, and by the Suhara Foundation.

  • Dr. Tamotsu Miyazaki is Professor Emeritus, Hokkaido University, Sapporo, Japan.

  • Abbreviations:
    TPO
    thrombopoietin
    IL-3
    interleukin-3
    EPO
    erythropoietin
    GEMM
    granulocyte/erythrocyte/macrophage/megakaryocyte
    GM
    granulocyte/macrophage
    PLC
    phospholipase C
    PKC
    protein kinase C
    JAK
    Janus kinase
    STAT
    signal transducer and activator of transcription
    MAPK
    mitogen-activated protein kinase
    FU
    fluorouracil
    Day-2 post 5-FU marrow cells
    bone marrow cells obtained from mice that had received 5-FU 2 days before
    Lin−
    lineage-negative
    Lin+
    lineage-positive
    Sca-1+
    stem cell antigen-positive
    KL
    kit ligand
    BSA
    bovine serum albumin
    TPA
    12-O-tetradecanoyl phorbol-13-acetate
    • Received August 16, 2000.
    • Accepted January 15, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET 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

Journal of Pharmacology and Experimental Therapeutics: 297 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 297, Issue 3
1 Jun 2001
  • 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 Journal of Pharmacology and Experimental Therapeutics 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.
Involvement of Protein Kinase C-ε in Signal Transduction of Thrombopoietin in Enhancement of Interleukin-3-Dependent Proliferation of Primitive Hematopoietic Progenitors
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleCELLULAR AND MOLECULAR

Involvement of Protein Kinase C-ε in Signal Transduction of Thrombopoietin in Enhancement of Interleukin-3-Dependent Proliferation of Primitive Hematopoietic Progenitors

Noriyuki Shiroshita, Manabu Musashi, Keisuke Sakurada, Kazuhiro Kimura, Yuzo Tsuda, Shuichi Ota, Hiroshi Iwasaki, Tamotsu Miyazaki, Takashi Kato, Hiroshi Miyazaki, Akihiro Shimosaka and Masahiro Asaka
Journal of Pharmacology and Experimental Therapeutics June 1, 2001, 297 (3) 868-875;

Citation Manager Formats

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

Involvement of Protein Kinase C-ε in Signal Transduction of Thrombopoietin in Enhancement of Interleukin-3-Dependent Proliferation of Primitive Hematopoietic Progenitors

Noriyuki Shiroshita, Manabu Musashi, Keisuke Sakurada, Kazuhiro Kimura, Yuzo Tsuda, Shuichi Ota, Hiroshi Iwasaki, Tamotsu Miyazaki, Takashi Kato, Hiroshi Miyazaki, Akihiro Shimosaka and Masahiro Asaka
Journal of Pharmacology and Experimental Therapeutics June 1, 2001, 297 (3) 868-875;
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

  • Zebrafish Gstp1 drug response
  • Comparison of Piceatannol with Resveratrol
  • Aldosterone synthesis in the heart
Show more Cellular and Molecular

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 JPET
  • 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
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

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