This Article
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 Honegger, A M
Right arrow Articles by Schlessinger, J
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Honegger, A M
Right arrow Articles by Schlessinger, J

 Previous Article  |  Next Article 

Mol Cell Biol. 1987 December; 7(12): 4568-4571

A mutant epidermal growth factor receptor with defective protein tyrosine kinase is unable to stimulate proto-oncogene expression and DNA synthesis.

A M Honegger, D Szapary, A Schmidt, R Lyall, E Van Obberghen, T J Dull, A Ullrich and J Schlessinger

Rorer Biotechnology, Inc., Rockville, Maryland 20850.

ABSTRACT

Cultured NIH-3T3 cells devoid of endogenous epidermal growth factor (EGF) receptors were transfected with cDNA expression constructs encoding either normal human EGF receptor or a receptor mutated in vitro at Lys-721, a residue that is thought to function as part of the ATP-binding site of the kinase domain. Unlike the wild-type EGF-receptor expressed in these cells, which exhibited EGF-dependent protein tyrosine kinase activity, the mutant receptor lacked protein tyrosine kinase activity and was unable to undergo autophosphorylation and to phosphorylate exogenous substrates. Despite this deficiency, the mutant receptor was normally expressed on the cell surface, and it exhibited both high- and low-affinity binding sites. The addition of EGF to cells expressing wild-type receptors caused the stimulation of various responses, including enhanced expression of proto-oncogenes c-fos and c-myc, morphological changes, and stimulation of DNA synthesis. However, in cells expressing mutant receptors, EGF was unable to stimulate these responses, suggesting that the tyrosine kinase activity is essential for EGF receptor signal transduction.

Mol Cell Biol. 1987 December; 7(12): 4568-4571




This article has been cited by other articles:

  • Yang, K. S., Ilagan, Ma. X. G., Piwnica-Worms, D., Pike, L. J. (2009). Luciferase Fragment Complementation Imaging of Conformational Changes in the Epidermal Growth Factor Receptor. J. Biol. Chem. 284: 7474-7482 [Abstract] [Full Text]  
  • Rothenberg, S. M., Engelman, J. A., Le, S., Riese, D. J. II, Haber, D. A., Settleman, J. (2008). Modeling oncogene addiction using RNA interference. Proc. Natl. Acad. Sci. USA 105: 12480-12484 [Abstract] [Full Text]  
  • Ozcan, F., Klein, P., Lemmon, M. A., Lax, I., Schlessinger, J. (2006). On the nature of low- and high-affinity EGF receptors on living cells. Proc. Natl. Acad. Sci. USA 103: 5735-5740 [Abstract] [Full Text]  
  • Stoorvogel, W., Kerstens, S., Fritzsche, I., Hartigh, J. C. d., Oud, R., van der Heyden, M. A. G., Voortman, J., van Bergen en Henegouwen, P. M. P. (2004). Sorting of Ligand-activated Epidermal Growth Factor Receptor to Lysosomes Requires Its Actin-binding Domain. J. Biol. Chem. 279: 11562-11569 [Abstract] [Full Text]  
  • Mattoon, D., Klein, P., Lemmon, M. A., Lax, I., Schlessinger, J. (2004). The tethered configuration of the EGF receptor extracellular domain exerts only a limited control of receptor function. Proc. Natl. Acad. Sci. USA 101: 923-928 [Abstract] [Full Text]  
  • Janmaat, M. L., Giaccone, G. (2003). Small-Molecule Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors. The Oncologist 8: 576-586 [Abstract] [Full Text]  
  • Prochazka, R., Kalab, P., Nagyova, E. (2003). Epidermal Growth Factor-Receptor Tyrosine Kinase Activity Regulates Expansion of Porcine Oocyte-Cumulus Cell Complexes In Vitro. Biol. Reprod. 68: 797-803 [Abstract] [Full Text]  
  • Musallam, L., Ethier, C., Haddad, P. S., Bilodeau, M. (2001). Role of EGF receptor tyrosine kinase activity in antiapoptotic effect of EGF on mouse hepatocytes. Am. J. Physiol. Gastrointest. Liver Physiol. 280: G1360-G1369 [Abstract] [Full Text]  
  • Kim, Y.-N., Wiepz, G. J., Guadarrama, A. G., Bertics, P. J. (2000). Epidermal Growth Factor-stimulated Tyrosine Phosphorylation of Caveolin-1. ENHANCED CAVEOLIN-1 TYROSINE PHOSPHORYLATION FOLLOWING ABERRANT EPIDERMAL GROWTH FACTOR RECEPTOR STATUS. J. Biol. Chem. 275: 7481-7491 [Abstract] [Full Text]  
  • Pollack, V. A., Savage, D. M., Baker, D. A., Tsaparikos, K. E., Sloan, D. E., Moyer, J. D., Barbacci, E. G., Pustilnik, L. R., Smolarek, T. A., Davis, J. A., Vaidya, M. P., Arnold, L. D., Doty, J. L., Iwata, K. K., Morin, M. J. (1999). Inhibition of Epidermal Growth Factor Receptor-Associated Tyrosine Phosphorylation in Human Carcinomas with CP-358,774: Dynamics of Receptor Inhibition In Situ and Antitumor Effects in Athymic Mice. J. Pharmacol. Exp. Ther. 291: 739-748 [Abstract] [Full Text]  
  • Wang, Z., Zhang, L., Yeung, T. K., Chen, X. (1999). Endocytosis Deficiency of Epidermal Growth Factor (EGF) Receptor-ErbB2 Heterodimers in Response to EGF Stimulation. Mol. Biol. Cell 10: 1621-1636 [Abstract] [Full Text]  
  • Glasgow, W. C., Hui, R., Everhart, A. L., Jayawickreme, S. P., Angerman-Stewart, J., Han, B.-B., Eling, T. E. (1997). The Linoleic Acid Metabolite, (13S)-Hydroperoxyoctadecadienoic Acid, Augments the Epidermal Growth Factor Receptor Signaling Pathway by Attenuation of Receptor Dephosphorylation. DIFFERENTIAL RESPONSE IN SYRIAN HAMSTER EMBRYO TUMOR SUPPRESSOR PHENOTYPES. J. Biol. Chem. 272: 19269-19276 [Abstract] [Full Text]  
  • Wu, J., Adamson, E. (1996). Kinase-negative mutant epidermal growth factor receptor (EGFR) expression during embryonal stem cell differentiation favours EGFR-independent lineages. Development 122: 3331-3342 [Abstract]  
  • Miloso, M., Mazzotti, M., Vass, W. C., Beguinot, L. (1995). SHC and GRB-2 Are Constitutively Activated by an Epidermal Growth Factor Receptor with a Point Mutation in the Transmembrane Domain. J. Biol. Chem. 270: 19557-19562 [Abstract] [Full Text]  
  • Alvarez, C. V., Shon, K.-J., Miloso, M., Beguinot, L. (1995). Structural Requirements of the Epidermal Growth Factor Receptor for Tyrosine Phosphorylation of eps8 and eps15, Substrates Lacking Src SH2 Homology Domains. J. Biol. Chem. 270: 16271-16276 [Abstract] [Full Text]  
  • Wright, J. D., Reuter, C. W. M., Weber, M. J. (1995). An Incomplete Program of Cellular Tyrosine Phosphorylations Induced by Kinase-defective Epidermal Growth Factor Receptors. J. Biol. Chem. 270: 12085-12093 [Abstract] [Full Text]  
  • Hipskind, R A, Buscher, D, Nordheim, A, Baccarini, M (1994). Ras/MAP kinase-dependent and -independent signaling pathways target distinct ternary complex factors.. Genes Dev. 8: 1803-1816 [Abstract]  
  • Koch, C., Anderson, D, Moran, M., Ellis, C, Pawson, T (1991). SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science 252: 668-674 [Abstract]  
  • Anderson, D, Koch, C., Grey, L, Ellis, C, Moran, M., Pawson, T (1990). Binding of SH2 domains of phospholipase C gamma 1, GAP, and Src to activated growth factor receptors. Science 250: 979-982 [Abstract]  
  • Yaish, P, Gazit, A, Gilon, C, Levitzki, A (1988). Blocking of EGF-dependent cell proliferation by EGF receptor kinase inhibitors. Science 242: 933-935 [Abstract]  
  • Caselli, A., Taddei, M. L., Manao, G., Camici, G., Ramponi, G. (2001). Tyrosine-phosphorylated Caveolin Is a Physiological Substrate of the Low Mr Protein-Tyrosine Phosphatase. J. Biol. Chem. 276: 18849-18854 [Abstract] [Full Text]  
  • Deb, T. B., Su, L., Wong, L., Bonvini, E., Wells, A., David, M., Johnson, G. R. (2001). Epidermal Growth Factor (EGF) Receptor Kinase-independent Signaling by EGF. J. Biol. Chem. 276: 15554-15560 [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»