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Gene Review

EGFR  -  epidermal growth factor receptor

Canis lupus familiaris

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Disease relevance of EGFR

  • The EGFR cleavage fragment was detected in the membrane blebs in addition to the cell pellets [1].
  • Epidermal growth factor (EGFR), oestrogen (ER), and progestin (PR) receptor concentrations were determined by radioligand binding assay in non-affected mammary tissues (n = 13) and benign (n = 11) and primary/locally recurrent malignant proliferative mammary lesions (n = 45) and metastases (n = 19) in 65 female dogs [2].
  • We have previously shown that 47% of radiation-induced lung neoplasms in dogs exhibit increased expression of epidermal growth factor receptor (EGFR) [3].
  • The transforming gene product of Fujinami sarcoma visue and EGF receptor kinase from A431 cells phosphorylated (Na+,K+)-ATPase poorly whereas casein was an excellent substrate [4].

High impact information on EGFR

  • Disruption of GRB2 interactions by microinjection of a peptide corresponding to the GRB2 SH2 domain or its phosphopeptide ligand blocked EGF receptor endocytosis; other SH2 domains that bind EGF receptors or antibodies that neutralize RAS did not [5].
  • Requirement for the adapter protein GRB2 in EGF receptor endocytosis [5].
  • At the same time, the endosome gives rise to multivesicular endosomes (MVB) enriched in EGFR and to 60-nm-diam basolateral vesicles [6].
  • At 20 degreesC dIgA-pIgR internalize to interconnected groups of vacuoles and tubules that comprise the endosomal compartment and in which they codistribute with internalized transferrin receptors (TR) and epidermal growth factor receptors (EGFR) [6].
  • However, this pure endosomal signaling of EGFR does not stimulate cell proliferation, because EGFR only remained activated for less than 2 h following its stimulation at endosomes, while DNA synthesis generally requires growth factor exposure for 8 h or more [7].

Biological context of EGFR


Anatomical context of EGFR

  • We propose that the differential sorting of occupied receptors within the MDCK endosome is achieved by this clathrin-based mechanism continuously retrieving receptors like TR from the pathways that deliver pIgR to the apical surface and EGFR to the lysosome [6].
  • In the present study, using the well-established Madin-Darby canine kidney C7 cell line, we tested the hypothesis that EGFR represents a negative-feedback control for chronic aldosterone-induced Na(+) reabsorption [amiloride-inhibitable short-circuit current (I(sc))] [10].
  • Together, these findings indicate that functional apical and basolateral EGFR exist on primary canine gastric epithelial cells and that these receptors regulate paracellular permeability [11].
  • It was concluded that in the dog mammary gland EGFR expression is not associated with conditions of steroid receptor absence of biological agressiveness of neoplastic growth [2].
  • In vascular smooth muscle cells the sodium pump complex can act as an intracellular signal transducing complex activated by low ouabain concentrations, which inhibit sufficient pumps to activate a transduction cascade via transactivation of EGFR, but insufficient pumps to alter intracellular ions [12].

Associations of EGFR with chemical compounds


Physical interactions of EGFR


Other interactions of EGFR


Analytical, diagnostic and therapeutic context of EGFR


  1. Cleavage of epidermal growth factor receptor by caspase during apoptosis is independent of its internalization. He, Y.Y., Huang, J.L., Chignell, C.F. Oncogene (2006) [Pubmed]
  2. Expression of epidermal growth factor receptor (EGFR) in non-affected and tumorous mammary tissue of female dogs. Rutteman, G.R., Foekens, J.A., Portengen, H., Vos, J.H., Blankenstein, M.A., Teske, E., Cornelisse, C.J., Misdorp, W. Breast Cancer Res. Treat. (1994) [Pubmed]
  3. Expression of transforming growth factor alpha in plutonium-239-induced lung neoplasms in dogs: investigations of autocrine mechanisms of growth. Gillett, N.A., Stegelmeier, B.L., Chang, I.Y., Kelly, G. Radiat. Res. (1991) [Pubmed]
  4. A tyrosine-specific protein kinase from Ehrlich ascites tumor cells. Nakamura, S., Braun, S., Racker, E. Arch. Biochem. Biophys. (1987) [Pubmed]
  5. Requirement for the adapter protein GRB2 in EGF receptor endocytosis. Wang, Z., Moran, M.F. Science (1996) [Pubmed]
  6. Sorting mechanisms regulating membrane protein traffic in the apical transcytotic pathway of polarized MDCK cells. Gibson, A., Futter, C.E., Maxwell, S., Allchin, E.H., Shipman, M., Kraehenbuhl, J.P., Domingo, D., Odorizzi, G., Trowbridge, I.S., Hopkins, C.R. J. Cell Biol. (1998) [Pubmed]
  7. Stimulation of cell proliferation by endosomal epidermal growth factor receptor as revealed through two distinct phases of signaling. Pennock, S., Wang, Z. Mol. Cell. Biol. (2003) [Pubmed]
  8. Endosomal signaling of epidermal growth factor receptor stimulates signal transduction pathways leading to cell survival. Wang, Y., Pennock, S., Chen, X., Wang, Z. Mol. Cell. Biol. (2002) [Pubmed]
  9. Ouabain-induced signaling and vascular smooth muscle cell proliferation. Aydemir-Koksoy, A., Abramowitz, J., Allen, J.C. J. Biol. Chem. (2001) [Pubmed]
  10. Evidence for epidermal growth factor receptor as negative-feedback control in aldosterone-induced Na+ reabsorption. Grossmann, C., Freudinger, R., Mildenberger, S., Krug, A.W., Gekle, M. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  11. Apical and basolateral EGF receptors regulate gastric mucosal paracellular permeability. Chen, M.C., Goliger, J., Bunnett, N., Soll, A.H. Am. J. Physiol. Gastrointest. Liver Physiol. (2001) [Pubmed]
  12. Low concentrations of ouabain activate vascular smooth muscle cell proliferation. Allen, J.C., Abramowitz, J., Koksoy, A. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  13. Elevated epidermal growth factor receptor binding in plutonium-induced lung tumors from dogs. Leung, F.C., Bohn, L.R., Dagle, G.E. Proc. Soc. Exp. Biol. Med. (1991) [Pubmed]
  14. Receptors for epidermal growth factor and estradiol in canine mammary tumors. Nerurkar, V.R., Seshadri, R., Mulherkar, R., Ishwad, C.S., Lalitha, V.S., Naik, S.N. Int. J. Cancer (1987) [Pubmed]
  15. Aldosterone interaction with epidermal growth factor receptor signaling in MDCK cells. Gekle, M., Freudinger, R., Mildenberger, S., Silbernagl, S. Am. J. Physiol. Renal Physiol. (2002) [Pubmed]
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