MIT Libraries homeMIT Libraries logoDSpace@MIT

MIT
View Item 
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Integration of multiple signaling pathway activities resolves K-RAS/N-RAS mutation paradox in colon epithelial cell response to inflammatory cytokine stimulation

Author(s)
Kreeger, Pamela K.; Wang, Yufang; Haigis, Kevin M.; Lauffenburger, Douglas A.
Thumbnail
DownloadKreeger Integr Biol 2010.pdf (1.340Mb)
PUBLISHER_POLICY

Publisher Policy

Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.

Terms of use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Metadata
Show full item record
Abstract
Colon tumors frequently harbor mutation in K-RAS and/or N-RAS, members of a GTPase family operating as a central hub for multiple key signaling pathways. While these proteins are strongly homologous, they exhibit diverse downstream effects on cell behavior. Utilizing an isogenic panel of human colon carcinoma cells bearing oncogenic mutations in K-RAS and/or N-RAS, we observed that K-RAS and double mutants similarly yield elevated apoptosis in response to treatment with TNFα compared to N-RAS mutants. Regardless, and in surprising contrast, key phospho-protein signals were more similar between N-RAS and dual mutants. This apparent contradiction could not be explained by any of the key signals individually, but a multi-pathway model constructed from the single-mutant cell line data was able to predict the behavior of the dual-mutant cell line. This success arises from a quantitative integration of multiple pro-apoptotic (pIκBα, pERK2) and pro-survival (pJNK, pHSP27) signals in manner not easily discerned from intuitive inspection.
Date issued
2010-03
URI
http://hdl.handle.net/1721.1/69155
Department
David H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biological Engineering
Journal
Integrative Biology
Publisher
Royal Society of Chemistry
Citation
Kreeger, Pamela K. et al. “Integration of multiple signaling pathway activities resolves K-RAS/N-RAS mutation paradox in colon epithelial cell response to inflammatory cytokine stimulation.” Integrative Biology 2.4 (2010): 202.
Version: Final published version
ISSN
1757-9694
1757-9708

Collections
  • MIT Open Access Articles

Browse

All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

My Account

Login

Statistics

OA StatisticsStatistics by CountryStatistics by Department
MIT Libraries homeMIT Libraries logo

Find us on

Twitter Facebook Instagram YouTube RSS

MIT Libraries navigation

SearchHours & locationsBorrow & requestResearch supportAbout us
PrivacyPermissionsAccessibility
MIT
Massachusetts Institute of Technology
Content created by the MIT Libraries, CC BY-NC unless otherwise noted. Notify us about copyright concerns.