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Gene Review

EGFR  -  epidermal growth factor receptor

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Disease relevance of EGFR

  • The antibodies were capable of isolating, as the major P-tyr-containing components, a 170kd protein (most likely the EGF receptor) from EGF-stimulated, 32P-labelled A431 cells, and 130kd and 60kd proteins from Rous sarcoma virus (RSV)-transformed chick cell lysate which had been labelled in vitro with gamma-32P-ATP [1].
  • This study demonstrates that the EGF receptor, partially purified from A431 epidermoid carcinoma cells, catalyzes the phosphorylation of one of the two clathrin light chains, clathrin light chain a (LCa) [2].

High impact information on EGFR

  • Because EGF receptor-mediated tyrosine phosphorylation of PLC-gamma 1 stimulates catalytic activity in vitro and G proteins have been implicated in the activation of PLC, we investigated which PLC isozymes are subject to G protein regulation [3].
  • Further, in functional assays of Gs employing S49 cyc- cell membranes, EGFR-13 increased the ability of Gs to stimulate adenylyl cyclase; phospho-EGFR-13 and a 14-aa peptide corresponding to a sequence in the cytosolic domain of the EGF receptor did not alter the functional activity of Gs [4].
  • As determined by phosphoamino acid analysis, the phosphorylation of Gsalpha by the EGFR kinase was exclusively on tyrosine residues [5].
  • Therefore, studies were performed to investigate the hypothesis that the EGFR protein tyrosine kinase phosphorylates Gsalpha and activates this protein [5].
  • Interestingly, GDP and guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) inhibited the phosphorylation of Gsalpha without altering EGFR autophosphorylation [5].

Biological context of EGFR

  • Using the antibody to mimic the receptor, other different anti-EGFR inhibitors as well as the small-molecule half-antigen itself were recognized directly from the crude extract of herb, which afforded us a novel promising approach for the efficient screening of lead compounds or drug candidates from natural resources [6].
  • In cell culture, ODN-dendrimer conjugates were effective in inhibiting cancer cell growth that correlated with a marked knockdown in EGFR protein expression [7].
  • The concentration of IFN alpha-2b at doubled IC50 to EGFR (6.55 x 10(3) IU/ml) only inhibited the cell growth by 25.13% [8].
  • In contrast, LPA-induced phosphorylation of Shc and ERK1/2 in clonal hepatocytes (C9 cells) was primarily mediated through MMP-dependent transactivation of the EGF-R [9].
  • These results suggest that the EGF receptor can mediate the prevention of apoptosis independently of both receptor-ligand binding and receptor kinase activity, and this activity is disrupted by the D813A mutation [10].

Anatomical context of EGFR


Associations of EGFR with chemical compounds

  • The array-designed antisense ODN was covalently conjugated to a novel anionic dendrimer using a pentaerythritol-based phosphoroamidite synthon via automated DNA synthesis and the ability of this conjugate to effectively deliver and down-regulate EGFR expression in cancer cells was evaluated [7].
  • In summary, stretch seems to enhance force generation via ERK signaling through an EGFR/src-dependent mechanism activated by peroxide derived from a stretch-mediated activation of the NAD(P)H oxidase, a response that may contribute to hypertensive alterations in vascular reactivity [14].
  • Hydrogen peroxide also elicited contraction through EGFR phosphorylation and ERK [14].
  • The effect of genistein on relaxation is probably not directly related to the EGF receptor [15].
  • When c.d. spectroscopy was used to monitor the effect of added phosphotyrosine-containing peptide on the structure of recombinant PLC gamma 1, significant spectral shifts, indicative of a conformational change, were observed upon complexation with the EGF-receptor phosphotyrosine-containing 12-residue peptide (Tyr*-992) [16].

Physical interactions of EGFR

  • The results suggest that cell surface Gal Tase interacts with a form of the EGF-R, having altered carbohydrate moieties to promote intracellular signaling for acinar cell proliferation [17].

Other interactions of EGFR

  • In vitro RNase H-mediated cleavage assays confirmed that covalently conjugated antisense ODNs in the dendrimer conjugate were able to hybridize and cleave the array-defined hybridisation target site within the EGFR mRNA without the need for ODN dissociation from the conjugate [7].
  • Furthermore, stretch caused an increase in EGFR phosphorylation and cytosolic to membrane translocation of the p47phox NAD(P)H oxidase subunit [14].
  • The accompanying manuscript (Kim J.W., Sim, S.S., Kim, U-H., Nishibe, S., Wahl, M. I., Carpenter, G., and Rhe, S. G. (1990) J. Biol. Chem. 265, 3940-3943) identifies these same 2 residues plus 2 additional tyrosine phosphorylation sites through large-scale in vitro phosphorylation of purified bovine brain PLC-gamma by the EGF receptor [18].
  • Thus, deregulation of PKC alpha, i.e. by increasing its expression levels in specific cells may affect, in turn the expression of cell surface receptors including the EGF receptor [12].
  • TGF beta 1 treatment of the anterior pituitary-derived cells also reduced the levels of c-myc and EGF receptor mRNA [19].

Analytical, diagnostic and therapeutic context of EGFR


  1. Preparation and characterization of antibodies to O-phosphotyrosine and their use for identification of phosphotyrosine-containing proteins. Ohtsuka, M., Ihara, S., Ogawa, R., Watanabe, T., Watanabe, Y. Int. J. Cancer (1984) [Pubmed]
  2. Differential in vitro phosphorylation of clathrin light chains by the epidermal growth factor receptor-associated protein tyrosine kinase and a pp60c-src-related spleen tyrosine kinase. Mooibroek, M.J., Cheng, H.C., Wang, J.H. Arch. Biochem. Biophys. (1992) [Pubmed]
  3. Activation of the beta 1 isozyme of phospholipase C by alpha subunits of the Gq class of G proteins. Taylor, S.J., Chae, H.Z., Rhee, S.G., Exton, J.H. Nature (1991) [Pubmed]
  4. A region in the cytosolic domain of the epidermal growth factor receptor antithetically regulates the stimulatory and inhibitory guanine nucleotide-binding regulatory proteins of adenylyl cyclase. Sun, H., Seyer, J.M., Patel, T.B. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  5. Activation of Gsalpha by the epidermal growth factor receptor involves phosphorylation. Poppleton, H., Sun, H., Fulgham, D., Bertics, P., Patel, T.B. J. Biol. Chem. (1996) [Pubmed]
  6. Frontal affinity chromatography combined on-line with mass spectrometry: a tool for the binding study of different epidermal growth factor receptor inhibitors. Zhu, L., Chen, L., Luo, H., Xu, X. Anal. Chem. (2003) [Pubmed]
  7. A novel anionic dendrimer for improved cellular delivery of antisense oligonucleotides. Hussain, M., Shchepinov, M., Sohail, M., Benter, I.F., Hollins, A.J., Southern, E.M., Akhtar, S. Journal of controlled release : official journal of the Controlled Release Society. (2004) [Pubmed]
  8. The inhibitory effects of IFN alpha-2b on EGFR expression and growth of cultured subconjunctival fibroblasts. Xiong, X., Wei, H., Du, S. J. Tongji Med. Univ. (1998) [Pubmed]
  9. Mechanisms of extracellularly regulated kinases 1/2 activation in adrenal glomerulosa cells by lysophosphatidic acid and epidermal growth factor. Shah, B.H., Baukal, A.J., Shah, F.B., Catt, K.J. Mol. Endocrinol. (2005) [Pubmed]
  10. Ligand- and kinase activity-independent cell survival mediated by the epidermal growth factor receptor expressed in 32D cells. Ewald, J.A., Wilkinson, J.C., Guyer, C.A., Staros, J.V. Exp. Cell Res. (2003) [Pubmed]
  11. Tri-iodothyronine induces proliferation in cultured bovine thyroid cells: evidence for the involvement of epidermal growth factor-associated tyrosine kinase activity. Di Fulvio, M., Coleoni, A.H., Pellizas, C.G., Masini-Repiso, A.M. J. Endocrinol. (2000) [Pubmed]
  12. Overexpression of protein kinase C alpha-subtype in Swiss/3T3 fibroblasts causes loss of both high and low affinity receptor numbers for epidermal growth factor. Eldar, H., Zisman, Y., Ullrich, A., Livneh, E. J. Biol. Chem. (1990) [Pubmed]
  13. Protein from chromaffin granules promotes survival of mesencephalic dopaminergic neurons by an EGF-receptor ligand-mediated mechanism. Krieglstein, K., Unsicker, K. J. Neurosci. Res. (1997) [Pubmed]
  14. Stretch enhances contraction of bovine coronary arteries via an NAD(P)H oxidase-mediated activation of the extracellular signal-regulated kinase mitogen-activated protein kinase cascade. Oeckler, R.A., Kaminski, P.M., Wolin, M.S. Circ. Res. (2003) [Pubmed]
  15. Role of protein tyrosine kinase on regulation of trabecular meshwork and ciliary muscle contractility. Wiederholt, M., Groth, J., Strauss, O. Invest. Ophthalmol. Vis. Sci. (1998) [Pubmed]
  16. src-homology 2 (SH2) domain ligation as an allosteric regulator: modulation of phosphoinositide-specific phospholipase C gamma 1 structure and activity. Koblan, K.S., Schaber, M.D., Edwards, G., Gibbs, J.B., Pompliano, D.L. Biochem. J. (1995) [Pubmed]
  17. Rat parotid gland acinar cell proliferation: signal transduction at the plasma membrane. Purushotham, K.R., Nakagawa, Y., Humphreys-Beher, M.G., Maeda, N., Schneyer, C.A. Crit. Rev. Oral Biol. Med. (1993) [Pubmed]
  18. Identification of two epidermal growth factor-sensitive tyrosine phosphorylation sites of phospholipase C-gamma in intact HSC-1 cells. Wahl, M.I., Nishibe, S., Kim, J.W., Kim, H., Rhee, S.G., Carpenter, G. J. Biol. Chem. (1990) [Pubmed]
  19. Transforming growth factor-beta (TGF beta) inhibits TGF alpha expression in bovine anterior pituitary-derived cells. Mueller, S.G., Kudlow, J.E. Mol. Endocrinol. (1991) [Pubmed]
  20. Electric field-directed cell motility involves up-regulated expression and asymmetric redistribution of the epidermal growth factor receptors and is enhanced by fibronectin and laminin. Zhao, M., Dick, A., Forrester, J.V., McCaig, C.D. Mol. Biol. Cell (1999) [Pubmed]
  21. Cholecystokinin does not affect the pancreatic contents of epidermal growth factor or its receptor. Ohlsson, B., Rehfeld, J.F., Sundler, F. Pancreas (2000) [Pubmed]
  22. Growth factors and corneal endothelial cells: II. Characterization of epidermal growth factor receptor from bovine corneal endothelial cells. Woost, P.G., Jumblatt, M.M., Eiferman, R.A., Schultz, G.S. Cornea (1992) [Pubmed]
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