The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

Links

 

Gene Review

EGFR  -  epidermal growth factor receptor

Bos taurus

 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

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

References

  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]
 
WikiGenes - Universities