This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Collin, G.
Right arrow Articles by Roche, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Collin, G.
Right arrow Articles by Roche, S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2007, p. 7631-7640, Vol. 27, No. 21
0270-7306/07/$08.00+0     doi:10.1128/MCB.00543-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Tom1L1-Clathrin Heavy Chain Complex Regulates Membrane Partitioning of the Tyrosine Kinase Src Required for Mitogenic and Transforming Activities{triangledown}

Guillaume Collin,{dagger} Mélanie Franco,{dagger},{ddagger} Valérie Simon, Christine Bénistant, and Serge Roche*

CNRS UMR5237, University of Montpellier 1 and 2, CRBM, 1919 route de Mende, 34293 Montpellier, France

Received 28 March 2007/ Returned for modification 14 May 2007/ Accepted 7 August 2007

Compartmentalization of Src tyrosine kinases (SFK) plays an important role in signal transduction induced by a number of extracellular stimuli. For example, Src mitogenic signaling induced by platelet-derived growth factor (PDGF) is initiated in cholesterol-enriched microdomain caveolae. How this Src subcellular localization is regulated is largely unknown. Here we show that the Tom1L1-clathrin heavy chain (CHC) complex negatively regulates the level of SFK in caveolae needed for the induction of DNA synthesis. Tom1L1 is both an interactor and a substrate of SFK. Intriguingly, it stimulates Src activity without promoting mitogenic signaling. We found that, upon association with CHC, Tom1L1 reduced the level of SFK in caveolae, thereby preventing its association with the PDGF receptor, which is required for the induction of mitogenesis. Similarly, the Tom1L1-CHC complex reduced also the level of oncogenic Src in cholesterol-enriched microdomains, thus affecting both its capacity to induce DNA synthesis and cell transformation. Conversely, Tom1L1, when not associated with CHC, accumulated in caveolae and promoted Src-driven DNA synthesis. We concluded that the Tom1L1-CHC complex defines a novel mechanism involved in negative regulation of mitogenic and transforming signals, by modulating SFK partitioning at the plasma membrane.

* Corresponding author. Mailing address: CNRS UMR5237, University of Montpellier 1 and 2, CRBM, 1919 route de Mende, 34293 Montpellier Cedex 05, France. Phone: 33 467 61 33 73. Fax: 33 467 52 15 59. E-mail: Serge.Roche{at}crbm.cnrs.fr

{triangledown} Published ahead of print on 4 September 2007.

{dagger} G.C. and M.F. made equal contributions to the manuscript.

{ddagger} Present address: Division of Molecular Oncology, IRCC University of Torino School of Medicine, 10060 Candiolo, Turin, Italy.

Molecular and Cellular Biology, November 2007, p. 7631-7640, Vol. 27, No. 21
0270-7306/07/$08.00+0     doi:10.1128/MCB.00543-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • St-Germain, J. R., Taylor, P., Tong, J., Jin, L. L., Nikolic, A., Stewart, I. I., Ewing, R. M., Dharsee, M., Li, Z., Trudel, S., Moran, M. F. (2009). Multiple myeloma phosphotyrosine proteomic profile associated with FGFR3 expression, ligand activation, and drug inhibition. Proc. Natl. Acad. Sci. USA 106: 20127-20132 [Abstract] [Full Text]  
  • Chen, Y., Veracini, L., Benistant, C., Jacobson, K. (2009). The transmembrane protein CBP plays a role in transiently anchoring small clusters of Thy-1, a GPI-anchored protein, to the cytoskeleton. J. Cell Sci. 122: 3966-3972 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»