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 Wang, Y.
Right arrow Articles by Wang, Z.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, Y.
Right arrow Articles by Wang, Z.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 2002, p. 7279-7290, Vol. 22, No. 20
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.20.7279-7290.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Endosomal Signaling of Epidermal Growth Factor Receptor Stimulates Signal Transduction Pathways Leading to Cell Survival

Yi Wang, Steven Pennock, Xinmei Chen, and Zhixiang Wang*

Department of Cell Biology and Signal Transduction Research Group, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada

Received 4 June 2002/ Returned for modification 2 July 2002/ Accepted 22 July 2002

In spite of intensified efforts to understand cell signaling from endosomes, there is no direct evidence demonstrating that endosomal signaling is sufficient to activate signal transduction pathways and no evidence to demonstrate that endosomal signaling is able to produce a biological outcome. The lack of breakthrough is due in part to the lack of means to generate endosomal signals without plasma membrane signaling. In this paper, we report the establishment of a system to specifically activate epidermal growth factor (EGF) receptor (EGFR) when it endocytoses into endosomes. We treated cells with EGF in the presence of AG-1478, a specific EGFR tyrosine kinase inhibitor, and monensin, which blocks the recycling of EGFR. This treatment led to the internalization of nonactivated EGF-EGFR complexes into endosomes. The endosome-associated EGFR was then activated by removing AG-1478 and monensin. During this procedure we did not observe any surface EGFR phosphorylation. We also achieved specific activation of endosome-associated EGFR without using monensin. By using this system, we provided original evidence demonstrating that (i) the endosome can serve as a nucleation site for the formation of signaling complexes, (ii) endosomal EGFR signaling is sufficient to activate the major signaling pathways leading to cell proliferation and survival, and (iii) endosomal EGFR signaling is sufficient to suppress apoptosis induced by serum withdrawal.

* Corresponding author. Mailing address: Department of Cell Biology and Signal Transduction Research Group, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada. Phone: (780) 492-0710. Fax: (780) 492-0450. E-mail: zwang{at}cellbnt.ualberta.ca.

Molecular and Cellular Biology, October 2002, p. 7279-7290, Vol. 22, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.20.7279-7290.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Jopling, H. M., Odell, A. F., Hooper, N. M., Zachary, I. C., Walker, J. H., Ponnambalam, S. (2009). Rab GTPase Regulation of VEGFR2 Trafficking and Signaling in Endothelial Cells. Arterioscler. Thromb. Vasc. Bio. 29: 1119-1124 [Abstract] [Full Text]  
  • Guo, H.-B., Johnson, H., Randolph, M., Lee, I., Pierce, M. (2009). Knockdown of GnT-Va expression inhibits ligand-induced downregulation of the epidermal growth factor receptor and intracellular signaling by inhibiting receptor endocytosis. Glycobiology 19: 547-559 [Abstract] [Full Text]  
  • Moulakakis, C., Stamme, C. (2009). Role of clathrin-mediated endocytosis of surfactant protein A by alveolar macrophages in intracellular signaling. Am. J. Physiol. Lung Cell. Mol. Physiol. 296: L430-L441 [Abstract] [Full Text]  
  • Cavet, M. E., Pang, J., Yin, G., Berk, B. C. (2008). An epidermal growth factor (EGF) -dependent interaction between GIT1 and sorting nexin 6 promotes degradation of the EGF receptor. FASEB J. 22: 3607-3616 [Abstract] [Full Text]  
  • Varghese, B., Barriere, H., Carbone, C. J., Banerjee, A., Swaminathan, G., Plotnikov, A., Xu, P., Peng, J., Goffin, V., Lukacs, G. L., Fuchs, S. Y. (2008). Polyubiquitination of Prolactin Receptor Stimulates Its Internalization, Postinternalization Sorting, and Degradation via the Lysosomal Pathway. Mol. Cell. Biol. 28: 5275-5287 [Abstract] [Full Text]  
  • Chamberlain, M. D., Chan, T., Oberg, J. C., Hawrysh, A. D., James, K. M., Saxena, A., Xiang, J., Anderson, D. H. (2008). Disrupted RabGAP Function of the p85 Subunit of Phosphatidylinositol 3-Kinase Results in Cell Transformation. J. Biol. Chem. 283: 15861-15868 [Abstract] [Full Text]  
  • Pennock, S., Wang, Z. (2008). A Tale of Two Cbls: Interplay of c-Cbl and Cbl-b in Epidermal Growth Factor Receptor Downregulation. Mol. Cell. Biol. 28: 3020-3037 [Abstract] [Full Text]  
  • Huang, M., DuHadaway, J. B., Prendergast, G. C., Laury-Kleintop, L. D. (2007). RhoB Regulates PDGFR- Trafficking and Signaling in Vascular Smooth Muscle Cells. Arterioscler. Thromb. Vasc. Bio. 27: 2597-2605 [Abstract] [Full Text]  
  • Balbis, A., Parmar, A., Wang, Y., Baquiran, G., Posner, B. I. (2007). Compartmentalization of Signaling-Competent Epidermal Growth Factor Receptors in Endosomes. Endocrinology 148: 2944-2954 [Abstract] [Full Text]  
  • Bonaccorsi, L., Nosi, D., Muratori, M., Formigli, L., Forti, G., Baldi, E. (2007). Altered endocytosis of epidermal growth factor receptor in androgen receptor positive prostate cancer cell lines. J Mol Endocrinol 38: 51-66 [Abstract] [Full Text]  
  • Takeshita, Y., Fujinaga, R., Zhao, C., Yanai, A., Shinoda, K. (2006). Huntingtin-associated protein 1 (HAP1) interacts with androgen receptor (AR) and suppresses SBMA-mutant-AR-induced apoptosis. Hum Mol Genet 15: 2298-2312 [Abstract] [Full Text]  
  • Khan, E. M., Heidinger, J. M., Levy, M., Lisanti, M. P., Ravid, T., Goldkorn, T. (2006). Epidermal Growth Factor Receptor Exposed to Oxidative Stress Undergoes Src- and Caveolin-1-dependent Perinuclear Trafficking. J. Biol. Chem. 281: 14486-14493 [Abstract] [Full Text]  
  • Arevalo, J. C., Pereira, D. B., Yano, H., Teng, K. K., Chao, M. V. (2006). Identification of a Switch in Neurotrophin Signaling by Selective Tyrosine Phosphorylation. J. Biol. Chem. 281: 1001-1007 [Abstract] [Full Text]  
  • Stoddart, A., Jackson, A. P., Brodsky, F. M. (2005). Plasticity of B Cell Receptor Internalization upon Conditional Depletion of Clathrin. Mol. Biol. Cell 16: 2339-2348 [Abstract] [Full Text]  
  • Weick, M., Wiedemann, P., Reichenbach, A., Bringmann, A. (2005). Resensitization of P2Y Receptors by Growth Factor-Mediated Activation of the Phosphatidylinositol-3 Kinase in Retinal Glial Cells. IOVS 46: 1525-1532 [Abstract] [Full Text]  
  • Valiathan, R. R., Resh, M. D. (2004). Expression of Human Immunodeficiency Virus Type 1 Gag Modulates Ligand-Induced Downregulation of EGF Receptor. J. Virol. 78: 12386-12394 [Abstract] [Full Text]  
  • Rohde, C. M., Schrum, J., Lee, A. W.-M. (2004). A Juxtamembrane Tyrosine in the Colony Stimulating Factor-1 Receptor Regulates Ligand-induced Src Association, Receptor Kinase Function, and Down-regulation. J. Biol. Chem. 279: 43448-43461 [Abstract] [Full Text]  
  • Hildreth, K. L., Wu, J.-H., Barak, L. S., Exum, S. T., Kim, L. K., Peppel, K., Freedman, N. J. (2004). Phosphorylation of the Platelet-derived Growth Factor Receptor-{beta} by G Protein-coupled Receptor Kinase-2 Reduces Receptor Signaling and Interaction with the Na+/H+ Exchanger Regulatory Factor. J. Biol. Chem. 279: 41775-41782 [Abstract] [Full Text]  
  • Boerner, J. L., Demory, M. L., Silva, C., Parsons, S. J. (2004). Phosphorylation of Y845 on the Epidermal Growth Factor Receptor Mediates Binding to the Mitochondrial Protein Cytochrome c Oxidase Subunit II. Mol. Cell. Biol. 24: 7059-7071 [Abstract] [Full Text]  
  • Le Stunff, H., Mikami, A., Giussani, P., Hobson, J. P, Jolly, P. S., Milstien, S., Spiegel, S. (2004). Role of Sphingosine-1-phosphate Phosphatase 1 in Epidermal Growth Factor-induced Chemotaxis. J. Biol. Chem. 279: 34290-34297 [Abstract] [Full Text]  
  • Lunin, V. V., Munger, C., Wagner, J., Ye, Z., Cygler, M., Sacher, M. (2004). The Structure of the MAPK Scaffold, MP1, Bound to Its Partner, p14: A COMPLEX WITH A CRITICAL ROLE IN ENDOSOMAL MAP KINASE SIGNALING. J. Biol. Chem. 279: 23422-23430 [Abstract] [Full Text]  
  • Balbis, A., Baquiran, G., Dumas, V., Posner, B. I. (2004). Effect of Inhibiting Vacuolar Acidification on Insulin Signaling in Hepatocytes. J. Biol. Chem. 279: 12777-12785 [Abstract] [Full Text]  
  • Wang, Y., Pennock, S. D., Chen, X., Kazlauskas, A., Wang, Z. (2004). Platelet-derived Growth Factor Receptor-mediated Signal Transduction from Endosomes. J. Biol. Chem. 279: 8038-8046 [Abstract] [Full Text]  
  • Schraufstatter, I. U., Trieu, K., Zhao, M., Rose, D. M., Terkeltaub, R. A., Burger, M. (2003). IL-8-Mediated Cell Migration in Endothelial Cells Depends on Cathepsin B Activity and Transactivation of the Epidermal Growth Factor Receptor. J. Immunol. 171: 6714-6722 [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]  
  • Pennock, S., Wang, Z. (2003). Stimulation of Cell Proliferation by Endosomal Epidermal Growth Factor Receptor As Revealed through Two Distinct Phases of Signaling. Mol. Cell. Biol. 23: 5803-5815 [Abstract] [Full Text]  
  • Li, S.-H., Yu, Z.-X., Li, C.-L., Nguyen, H.-P., Zhou, Y.-X., Deng, C., Li, X.-J. (2003). Lack of Huntingtin-Associated Protein-1 Causes Neuronal Death Resembling Hypothalamic Degeneration in Huntington's Disease. J. Neurosci. 23: 6956-6964 [Abstract] [Full Text]  
  • Wang, Y., Pennock, S., Chen, X., Wang, Z. (2002). Internalization of Inactive EGF Receptor into Endosomes and the Subsequent Activation of Endosome-Associated EGF Receptors. Sci Signal 2002: pl17-pl17 [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»