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 Xu, L.
Right arrow Articles by Foster, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xu, L.
Right arrow Articles by Foster, D. A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2003, p. 645-654, Vol. 23, No. 2
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.2.645-654.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Elevated Phospholipase D Activity in H-Ras- but Not K-Ras-Transformed Cells by the Synergistic Action of RalA and ARF6

Lizhong Xu,1 Paul Frankel,1,{dagger} Desmond Jackson,1 Thuy Rotunda,1 Rita L. Boshans,2 Crislyn D'Souza-Schorey,2 and David A. Foster1*

Department of Biological Sciences, Hunter College of The City University of New York, New York, New York 10021,1 Department of Biological Sciences and the Walther Cancer Institute, University of Notre Dame, Notre Dame, Indiana 465562

Received 14 June 2002/ Returned for modification 11 July 2002/ Accepted 21 October 2002

Phospholipase D (PLD) activity is elevated in response to the oncogenic stimulus of H-Ras but not K-Ras. H-Ras and K-Ras have been reported to localize to different membrane microdomains, with H-Ras localizing to caveolin-enriched light membrane fractions. We reported previously that PLD activity elevated in response to mitogenic stimulation is restricted to the caveolin-enriched light membrane fractions. PLD activity in H-Ras-transformed cells is dependent upon RalA, and consistent with a lack of elevated PLD activity in K-Ras-transformed cells, RalA was not activated in K-Ras-transformed cells. Although H-Ras-induced PLD activity is dependent upon RalA, an activated mutant of RalA is not sufficient to elevate PLD activity. We reported previously that RalA interacts with PLD activating ADP ribosylation factor (ARF) proteins. In cells transformed by H-Ras, we found increased coprecipitation of ARF6 with RalA. Moreover, ARF6 colocalized with RalA in light membrane fractions. Interestingly, ARF6 protein levels were elevated in H-Ras- but not K-Ras-transformed cells. A dominant-negative mutant of ARF6 inhibited PLD activity in H-Ras-transformed NIH 3T3 cells. Activated mutants of either ARF6 or RalA were not sufficient to elevate PLD activity in NIH 3T3 cells; however, expression of both activated RalA and activated ARF6 in NIH 3T3 cells led to increased PLD activity. These data suggest a model whereby H-Ras stimulates the activation of both RalA and ARF6, which together lead to the elevation of PLD activity.

* Corresponding author. Mailing address: Department of Biological Sciences, Hunter College of The City University of New York, 695 Park Ave., New York, NY 10021. Phone: (212) 772-4075. Fax: (212) 772-5227. E-mail: foster{at}genectr.hunter.cuny.edu.

{dagger} Present address: Cancer Research UK Centre for Cell and Molecular Biology, Chester Beatty Laboratories, Institute of Cancer Research, London SW3 6JB, United Kingdom.

Molecular and Cellular Biology, January 2003, p. 645-654, Vol. 23, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.2.645-654.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Garcia, A., Zheng, Y., Zhao, C., Toschi, A., Fan, J., Shraibman, N., Brown, H. A., Bar-Sagi, D., Foster, D. A., Arbiser, J. L. (2008). Honokiol Suppresses Survival Signals Mediated by Ras-Dependent Phospholipase D Activity in Human Cancer Cells. Clin. Cancer Res. 14: 4267-4274 [Abstract] [Full Text]  
  • Smith, S. C., Oxford, G., Baras, A. S., Owens, C., Havaleshko, D., Brautigan, D. L., Safo, M. K., Theodorescu, D. (2007). Expression of Ral GTPases, Their Effectors, and Activators in Human Bladder Cancer. Clin. Cancer Res. 13: 3803-3813 [Abstract] [Full Text]  
  • Zheng, Y., Rodrik, V., Toschi, A., Shi, M., Hui, L., Shen, Y., Foster, D. A. (2006). Phospholipase D Couples Survival and Migration Signals in Stress Response of Human Cancer Cells. J. Biol. Chem. 281: 15862-15868 [Abstract] [Full Text]  
  • Lalli, G., Hall, A. (2005). Ral GTPases regulate neurite branching through GAP-43 and the exocyst complex. JCB 171: 857-869 [Abstract] [Full Text]  
  • Gomez, G. A., Daniotti, J. L. (2005). H-Ras Dynamically Interacts with Recycling Endosomes in CHO-K1 Cells: INVOLVEMENT OF Rab5 AND Rab11 IN THE TRAFFICKING OF H-Ras TO THIS PERICENTRIOLAR ENDOCYTIC COMPARTMENT. J. Biol. Chem. 280: 34997-35010 [Abstract] [Full Text]  
  • Sidhu, R. S., Clough, R. R., Bhullar, R. P. (2005). Regulation of Phospholipase C-{delta}1 through Direct Interactions with the Small GTPase Ral and Calmodulin. J. Biol. Chem. 280: 21933-21941 [Abstract] [Full Text]  
  • Buchanan, F. G., McReynolds, M., Couvillon, A., Kam, Y., Holla, V. R., DuBois, R. N., Exton, J. H. (2005). Requirement of phospholipase D1 activity in H-RasV12-induced transformation. Proc. Natl. Acad. Sci. USA 102: 1638-1642 [Abstract] [Full Text]  
  • Norman, K. L., Hirasawa, K., Yang, A.-D., Shields, M. A., Lee, P. W. K. (2004). Reovirus oncolysis: The Ras/RalGEF/p38 pathway dictates host cell permissiveness to reovirus infection. Proc. Natl. Acad. Sci. USA 101: 11099-11104 [Abstract] [Full Text]  
  • Sunaga, N., Miyajima, K., Suzuki, M., Sato, M., White, M. A., Ramirez, R. D., Shay, J. W., Gazdar, A. F., Minna, J. D. (2004). Different Roles for Caveolin-1 in the Development of Non-Small Cell Lung Cancer versus Small Cell Lung Cancer. Cancer Res. 64: 4277-4285 [Abstract] [Full Text]  
  • Takaya, A., Ohba, Y., Kurokawa, K., Matsuda, M. (2004). RalA Activation at Nascent Lamellipodia of Epidermal Growth Factor-stimulated Cos7 Cells and Migrating Madin-Darby Canine Kidney Cells. Mol. Biol. Cell 15: 2549-2557 [Abstract] [Full Text]  
  • Foster, D. A., Xu, L. (2003). Phospholipase D in Cell Proliferation and Cancer. Mol Cancer Res 1: 789-800 [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»