This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ehrhardt, A. Articles by Schrader, J. W. Search for Related Content PubMed PubMed Citation Articles by Ehrhardt, A. Articles by Schrader, J. W.

Distinct Mechanisms Determine the Patterns of Differential Activation of H-Ras, N-Ras, K-Ras 4B, and M-Ras by Receptors for Growth Factors or Antigen

The Biomedical Research Centre, University of British Columbia, Vancouver, CanadaComprehensive Cancer Center, University of Alabama at Birmingham, BirminghamAlabama,^{1 2}

Received 15 September 2003/ Returned for modification 28 November 2003/ Accepted 13 April 2004

Although GTPases of the Ras family have been implicated in many aspects of the regulation of cells, little is known about the roles of individual family members. Here, we analyzed the mechanisms of activation of H-Ras, N-Ras, K-Ras 4B, and M-Ras by two types of external stimuli, growth factors and ligation of the antigen receptors of B or T lymphocytes (BCRs and TCRs). The growth factors interleukin-3, colony-stimulating factor 1, and epidermal growth factor all preferentially activated M-Ras and K-Ras 4B over H-Ras or N-Ras. Preferential activation of M-Ras and K-Ras 4B depended on the presence of their polybasic carboxy termini, which directed them into high-buoyant-density membrane domains where the activated receptors, adapters, and mSos were also present. In contrast, ligation of the BCR or TCR resulted in activation of H-Ras, N-Ras, and K-Ras 4B, but not M-Ras. This pattern of activation was not influenced by localization of the Ras proteins to membrane domains. Activation of H-Ras, N-Ras, and K-Ras 4B instead depended on the presence of phospholipase C- and RasGRP. Thus, the molecular mechanisms leading to activation of Ras proteins vary with the stimulus and can be influenced by either colocalization with activated receptors or differential sensitivity to the exchange factors activated by a stimulus.

This article has been cited by other articles:

• Teraishi, F., Guo, W., Zhang, L., Dong, F., Davis, J. J., Sasazuki, T., Shirasawa, S., Liu, J., Fang, B. (2006). Activation of Sterile20-Like Kinase 1 in Proteasome Inhibitor Bortezomib-Induced Apoptosis in Oncogenic K-ras-Transformed Cells.. Cancer Res. 66: 6072-6079 [Abstract] [Full Text]  
• Wang, Y., Wu, J., Wang, Z. (2006). Akt Binds to and Phosphorylates Phospholipase C-{gamma}1 in Response to Epidermal Growth Factor. Mol. Biol. Cell 17: 2267-2277 [Abstract] [Full Text]  
• Tuthill, M. C., Oki, C. E., Lorenzo, P. S. (2006). Differential effects of bryostatin 1 and 12-O-tetradecanoylphorbol-13-acetate on the regulation and activation of RasGRP1 in mouse epidermal keratinocytes.. Molecular Cancer Therapeutics 5: 602-610 [Abstract] [Full Text]  
• David, M. D., Cochrane, C. L., Duncan, S. K., Schrader, J. W. (2005). Pure Lipopolysaccharide or Synthetic Lipid A Induces Activation of p21Ras in Primary Macrophages through a Pathway Dependent on Src Family Kinases and PI3K. J. Immunol. 175: 8236-8241 [Abstract] [Full Text]  
• Coughlin, J. J., Stang, S. L., Dower, N. A., Stone, J. C. (2005). RasGRP1 and RasGRP3 Regulate B Cell Proliferation by Facilitating B Cell Receptor-Ras Signaling. J. Immunol. 175: 7179-7184 [Abstract] [Full Text]  
• Dasgupta, B., Li, W., Perry, A., Gutmann, D. H. (2005). Glioma Formation in Neurofibromatosis 1 Reflects Preferential Activation of K-RAS in Astrocytes. Cancer Res. 65: 236-245 [Abstract] [Full Text]