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 Matallanas, D.
Right arrow Articles by Crespo, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Matallanas, D.
Right arrow Articles by Crespo, P.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2006, p. 100-116, Vol. 26, No. 1
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.1.100-116.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Distinct Utilization of Effectors and Biological Outcomes Resulting from Site-Specific Ras Activation: Ras Functions in Lipid Rafts and Golgi Complex Are Dispensable for Proliferation and Transformation

David Matallanas,1,{dagger} Victoria Sanz-Moreno,1,{dagger} Imanol Arozarena,1 Fernando Calvo,1 Lorena Agudo-Ibáñez,1 Eugenio Santos,2 María T. Berciano,3 and Piero Crespo1*

Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas (CSIC), Departamento de Biología Molecular,1 Departamento de Anatomía y Biología Celular, Unidad de Biomedicina, CSIC-Universidad de Cantabria, Santander 39011, Spain,3 Centro de Investigación del Cancer, IBMCC, CSIC-Universidad de Salamanca, Salamanca 37007, Spain2

Received 4 May 2005/ Returned for modification 2 June 2005/ Accepted 6 October 2005

Ras proteins are distributed in different types of plasma membrane microdomains and endomembranes. However, how microlocalization affects the signals generated by Ras and its subsequent biological outputs is largely unknown. We have approached this question by selectively targeting RasV12 to different cellular sublocalizations. We show here that compartmentalization dictates Ras utilization of effectors and the intensity of its signals. Activated Ras can evoke enhanced proliferation and transformation from most of its platforms, with the exception of the Golgi complex. Furthermore, signals that promote survival emanate primarily from the endoplasmic reticulum pool. In addition, we have investigated the need for the different pools of endogenous Ras in the conveyance of upstream mitogenic and transforming signals. Using targeted RasN17 inhibitory mutants and in physiological contexts such as H-Ras/N-Ras double knockout fibroblasts, we demonstrate that Ras functions at lipid rafts and at the Golgi complex are fully dispensable for proliferation and transformation.

* Corresponding author. Mailing address: Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas (CSIC). Unidad de Biomedicina, CSIC-Universidad de Cantabria. Departamento de Biología Molecular Facultad de Medicina, C/ Cardenal Herrera Oria s/n, Santander 39011, Spain. Phone: 34-942-200959. Fax: 34-942-201945. E-mail: pcrespo{at}iib.uam.es.

{dagger} D.M. and V.S.-M. contributed equally to this study.

Molecular and Cellular Biology, January 2006, p. 100-116, Vol. 26, No. 1
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.1.100-116.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Calvo, F., Crespo, P. (2009). Structural and Spatial Determinants Regulating TC21 Activation by RasGRF Family Nucleotide Exchange Factors. Mol. Biol. Cell 20: 4289-4302 [Abstract] [Full Text]  
  • Casar, B., Arozarena, I., Sanz-Moreno, V., Pinto, A., Agudo-Ibanez, L., Marais, R., Lewis, R. E., Berciano, M. T., Crespo, P. (2009). Ras Subcellular Localization Defines Extracellular Signal-Regulated Kinase 1 and 2 Substrate Specificity through Distinct Utilization of Scaffold Proteins. Mol. Cell. Biol. 29: 1338-1353 [Abstract] [Full Text]  
  • Inder, K., Harding, A., Plowman, S. J., Philips, M. R., Parton, R. G., Hancock, J. F. (2008). Activation of the MAPK Module from Different Spatial Locations Generates Distinct System Outputs. Mol. Biol. Cell 19: 4776-4784 [Abstract] [Full Text]  
  • Eisenberg, S., Shvartsman, D. E., Ehrlich, M., Henis, Y. I. (2006). Clustering of raft-associated proteins in the external membrane leaflet modulates internal leaflet h-ras diffusion and signaling.. Mol. Cell. Biol. 26: 7190-7200 [Abstract] [Full Text]  
  • Wright, L. P., Philips, M. R. (2006). Thematic review series: Lipid Posttranslational Modifications CAAX modification and membrane targeting of Ras. J. Lipid Res. 47: 883-891 [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»