This website does readability filtering of other pages. All styles, scripts, forms and ads are stripped. If you want your website excluded or have other feedback, use this form.

K- and N-Ras Are Geranylgeranylated in Cells Treated with Farnesyl Protein Transferase Inhibitors

Advertisement Advertisement

Sign In »

Skip to main page content

K- and N-Ras Are Geranylgeranylated in Cells Treated with Farnesyl Protein Transferase Inhibitors*

  1. David B. Whyte,
  2. Paul Kirschmeier,
  3. Tish N. Hockenberry,
  4. Irma Nunez-Oliva,
  5. Linda James,
  6. Joseph J. Catino,
  7. W. Robert Bishop and
  8. Jin-Keon Pai
  1. From the Department of Tumor Biology, Schering-Plough Research Institute, Kenilworth, New Jersey 07033


The association of mutant forms of Ras protein with a variety of human cancers has stimulated intense interest in therapies based on inhibiting oncogenic Ras signaling. Attachment of Ras proteins to the plasma membrane is required for effective Ras signaling and is initiated by the enzyme farnesyl protein transferase. We found that in the presence of potent farnesyl protein transferase inhibitors, Ras proteins in the human colon carcinoma cell line DLD-1 were alternatively prenylated by geranylgeranyl transferase-1. When H-Ras, N-Ras, K-Ras4A, and K-Ras4B were expressed individually in COS cells, H-Ras prenylation and membrane association were found to be uniquely sensitive to farnesyl transferase inhibitors; N- and K-Ras proteins incorporated the geranylgeranyl isoprene group and remained associated with the membrane fraction. The alternative prenylation of N- and K-Ras has significant implications for our understanding of the mechanism of action of farnesyl protein transferase inhibitors as anti-cancer chemotherapeutics.


  • * The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • ‡ To whom correspondence should be addressed: Schering Plough Research Institute, Bldg. K15–4/4600, 2015 Galloping Hill Rd., Kenilworth, NJ 07033. Tel.: 908-298-7346; Fax: 908-298-7115; E-mail:david.whyte{at}

  • Received November 7, 1996.
  • Revision received March 14, 1997.
  • CiteULike
  • Delicious
  • Digg
  • Facebook
  • Google+
  • LinkedIn
  • Mendeley
  • Twitter

What's this?

View this article with LENS Prev Next Table of Contents

This Article

  1. doi: 10.1074/jbc.272.22.14459 May 30, 1997 The Journal of Biological Chemistry 272, 14459-14464.
  1. » Abstract(Free)
  2. Full Text(Free)
  3. PDF(Free)


Article Usage Stats

  1. Article Usage Statistics


  1. Email this article to a friend
  2. Alert me when this article is cited
  3. Alert me if a correction is posted
  4. Alert me when eletters are published
  5. Similar articles in this journal
  6. Similar articles in Web of Science
  7. Similar articles in PubMed
  8. Download to citation manager
  9. Request Permissions


  1. Submit a Letter to the Editor

Citing Articles

  1. Load citing article information
  2. Citing articles via Web of Science
  3. Citing articles via Google Scholar

Google Scholar

  1. Articles by Whyte, D. B.
  2. Articles by Pai, J. K.
  3. Search for related content


  1. PubMed citation
  2. Articles by Whyte, D. B.
  3. Articles by Pai, J. K.

Related Content

  1. Load related web page information

Social Bookmarking

    • CiteULike
    • Delicious
    • Digg
    • Facebook
    • Google+
    • LinkedIn
    • Mendeley
    • Twitter

    What's this?

Submit your work to JBC.

You'll be in good company.



Journal of Lipid Research

Molecular & Cellular Proteomics

Copyright © 2018 American Society for Biochemistry and Molecular Biology Privacy Policy Online ISSN 1083-351X
  • Advertisement