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

RanGAP-Mediated Nuclear Protein Import in Vascular Smooth Muscle Cells Is Augmented by Lysophosphatidylcholine

Randolph S. Faustino, Lyle N. W. Stronger, Melanie N. Richard, Michael P. Czubryt, David A. Ford, Michele A. Prociuk, Elena Dibrov and Grant N. Pierce
Molecular Pharmacology February 2007, 71 (2) 438-445; DOI: https://doi.org/10.1124/mol.105.021667
Randolph S. Faustino
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lyle N. W. Stronger
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Melanie N. Richard
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael P. Czubryt
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David A. Ford
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michele A. Prociuk
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elena Dibrov
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Grant N. Pierce
  • 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

The intracellular mechanism responsible for the mitogenic effects of lysophosphatidylcholine (LPC) is unclear. Import of proteins from the cytoplasm into the cell nucleus is integral to the regulation of gene expression and cell growth. We hypothesized that LPC exerts its intracellular effects through alterations in nuclear protein import. Rabbit aortic smooth muscle cells incubated with LPC induced a significant increase in cell proliferation in both quiescent cells (63.2 ± 6.48% of control) and cells grown in 1% fetal bovine serum (FBS) (28.3 ± 7.35% of control). Vascular smooth muscle cells were preincubated with LPC then microinjected with a marker protein for nuclear import. A significant stimulation of nuclear protein transport was observed. Using a conventional nuclear protein import assay in permeabilized cells, a significant stimulation of import (72.3 ± 5.2% of control) was again observed when the cytosolic nuclear import cocktail was treated with LPC. This effect was not observed with other lysophosphatidyl species. LPC also activated the extracellular signal-regulated kinase (ERK) ½ mitogen-activated protein kinase (MAPK) pathway, and this was blocked by 2′-amino-3′-methoxyflavone (PD98059), which inhibits the activation of ERK ½. The stimulation of nuclear import was also blocked by PD98059. LPC-induced MAPK activation augmented GTP hydrolysis by RanGAP, a RanGTPase activating protein and a critical regulatory component of nuclear protein import, and this stimulation was again blocked by PD98059. We conclude that LPC alters gene expression and cell proliferation through striking effects on nuclear protein import via a MAP kinase-induced activation of RanGAP. This may play an important role in cancer and atherosclerosis and other disorders involving accelerated cell growth/proliferation.

Footnotes

  • This work was supported by a grant from the Canadian Institutes for Health Research. D.F. is supported by the National Institutes of Health (grant R01-HL42665) and the Washington University Mass Spectrometry Resource (grant RR00954). MN Richard was supported by a Canadian Graduate Student Master's Award (Canadian Institutes of Health Research Scholarship).

  • This work was presented in poster form at the XVIII World Congress International Society for Heart Research; August 7-11, 2004; Brisbane, Australia.

  • ABBREVIATIONS: LPC, lysophosphatidylcholine; NLS, nuclear localization sequence; NPC, nuclear pore complex; DMEM, Dulbecco's modified Eagle's medium; FBS, fetal bovine serum; BSA, bovine serum albumin; ERK, extracellular signal-regulated kinase; MEK, mitogen-activated protein kinase kinase; PD98059, 2′-amino-3′-methoxyflavone; LPE, lysophosphatidylethanolamine; LPI, lysophosphatidylinositol; LPS, lysophosphatidylserine; LPLC, lysoplasmenylcholine; MAP, mitogen-activated protein; MAPK, mitogen-activated protein kinase; DTT, dithiothreitol; GMP-PNP, guanosine-5′-(β-γ-imido)-triphosphate.

    • Received December 12, 2005.
    • Accepted November 14, 2006.
  • 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: 71 (2)
Molecular Pharmacology
Vol. 71, Issue 2
1 Feb 2007
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
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.
RanGAP-Mediated Nuclear Protein Import in Vascular Smooth Muscle Cells Is Augmented by Lysophosphatidylcholine
(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

RanGAP-Mediated Nuclear Protein Import in Vascular Smooth Muscle Cells Is Augmented by Lysophosphatidylcholine

Randolph S. Faustino, Lyle N. W. Stronger, Melanie N. Richard, Michael P. Czubryt, David A. Ford, Michele A. Prociuk, Elena Dibrov and Grant N. Pierce
Molecular Pharmacology February 1, 2007, 71 (2) 438-445; DOI: https://doi.org/10.1124/mol.105.021667

Citation Manager Formats

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

Share
Research ArticleArticle

RanGAP-Mediated Nuclear Protein Import in Vascular Smooth Muscle Cells Is Augmented by Lysophosphatidylcholine

Randolph S. Faustino, Lyle N. W. Stronger, Melanie N. Richard, Michael P. Czubryt, David A. Ford, Michele A. Prociuk, Elena Dibrov and Grant N. Pierce
Molecular Pharmacology February 1, 2007, 71 (2) 438-445; DOI: https://doi.org/10.1124/mol.105.021667
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 Articles

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