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Epidermal Growth Factor Receptor Function
Published by Anonymous on 2007/9/29 (2007 reads)
1: Ugeskr Laeger. 2006 Jun 12;168(24):2354-61.


[Mutations in the epidermal growth factor receptor: structure and biological function in human tumors]

[Article in Danish]

Pedersen MW, Poulsen HS.

H:S Rigshospitalet, Finsencentret, Strålebiologisk Laboratorium, Afsnit 6321, DK-2100 København Ø.

The epidermal growth factor receptor (EGFR) plays an important role in the regulation of normal cell proliferation, differentiation and survival. For this reason EGFR status is often altered in a range of human tumor types and generally correlates with a poor prognosis. In recent years a number of mutations in the EGFR gene have been noted that lead to the expression of overactive or constitutively active aberrant receptors. These receptors have been shown to participate actively in the process of tumor genesis. This review provides an overview of the structure of these mutations and their biological function in human tumors plus the potentials of anticancer therapy.

Publication Types:
English Abstract
Research Support, Non-U.S. Gov't
Review

PMID: 16822420 [PubMed - indexed for MEDLINE]

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2: Cancer Lett. 2004 Apr 8;206(2):129-35.


Green fluorescent protein as a tool to study epidermal growth factor receptor function.

Hayes N, Howard-Cofield E, Gullick W.

Cancer Biology Laboratory, Research School of Biosciences, University of Kent at Canterbury, Canterbury, Kent CT2 7NJ, UK.

The subcellular distribution of the epidermal growth factor receptor and its interaction with second messenger proteins has been explored using tagging with green fluorescent protein and its derivatives. EGFR itself has been fused with GFP and its natural life cycle and its internalisation in response to ligand determined. Several second messenger proteins including Shc and PI3kinase have also been tagged with fluorescent proteins and their subcellular redistribution in response to ligand activation has been filmed. The physical interaction of the EGFR with second messengers has been studied by FRET and other proximity assays. These systems will not only reveal much about the behaviour of the system in live cells but may also be useful for observing the effects of signal transduction inhibitor drugs such as antibodies and small molecule tyrosine kinase inhibitors. Finally, they have the potential to be developed into screens for new compounds which affect the system.

Publication Types:
Review

PMID: 15013518 [PubMed - indexed for MEDLINE]

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3: Biochem Pharmacol. 2000 Oct 15;60(8):1217-23.


Role of conformational alteration in the epidermal growth factor receptor (EGFR) function.

Bishayee S.

Pathology and Laboratory Medicine, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA. bishayee@umdnj.edu

This mini-review addresses the effect of glycosylation and phosphorylation on the conformational alterations of the epidermal growth factor receptor (EGFR). Based on studies with full-length and truncated EGFRs, we propose a model to suggest that receptor-receptor self-association, which occurs in the truncated receptor and depends on core glycosylation, is prevented in intact receptor by a certain extracellular domain and that the function of the ligand is to remove the negative constraint. We also propose, based on works with a conformation-specific antibody directed to an unphosphorylated peptide, that the interactions among negatively charged phosphotyrosine residues in the receptor molecule result in bringing two epitopes separated by a long stretch of amino acids close to each other to form an antibody-binding site. The implications of these posttranslational modifications on receptor functions are also discussed in this article.

Publication Types:
Review

PMID: 11007960 [PubMed - indexed for MEDLINE]

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4: Ann Oncol. 1997 Dec;8(12):1197-206.


Epidermal growth factor receptor (EGFR) and EGFR mutations, function and possible role in clinical trials.

Voldborg BR, Damstrup L, Spang-Thomsen M, Poulsen HS.

Section for Radiation Biology, Finsen Centre, Rigshospitalet, Copenhagen, Denmark.

The epidermal growth factor receptor (EGFR) is a growth factor receptor that induces cell differentiation and proliferation upon activation through the binding of one of its ligands. The receptor is located at the cell surface, where the binding of a ligand activates a tyrosine kinase in the intracellular region of the receptor. This tyrosine kinase phosphorylates a number of intracellular substrates that activates pathways leading to cell growth, DNA synthesis and the expression of oncogenes such as fos and jun. EGFR is thought to be involved the development of cancer, as the EGFR gene is often amplified, and/or mutated in cancer cells. In this review we will focus on: (I) the structure and function of EGFR, (II) implications of receptor/ligand coexpression and EGFR mutations or overexpression, (III) its effect on cancer cells, (IV) the development of the malignant phenotype and (V) the clinical aspects of therapeutic targeting of EGFR.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 9496384 [PubMed - indexed for MEDLINE]

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5: Bioessays. 1995 Oct;17(10):839-46.


Epidermal growth factor receptor function in early mammalian development.

Wiley LM, Adamson ED, Tsark EC.

Department of Obstetrics and Gynecology, University of California, Davis 95616, USA.

We review here the data indicating a role for epidermal growth factor receptor (EGF receptor) signalling in early mouse development. Embryonic development of the metazoan embryo generally begins with the formation of a cystic structure and epithelial layers that subsequently form anlagen of the definitive body parts and organs. For the mammalian embryo, this cystic structure is a blastocyst whose wall consists of trophectoderm, the first epithelium to develop during mammalian embryogenesis. The onset of expression and function of EGF receptors is coincident with the onset of trophectoderm development. Modulating EGF receptor expression and function modulates trophectoderm differentiation, leading to the hypothesis that functional EGF receptors participate in the induction of trophectoderm development and perhaps of other embryonic epithelial derivatives such as nervous tissues.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 7487966 [PubMed - indexed for MEDLINE]

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6: Nippon Rinsho. 1992 Aug;50(8):1885-92.


[Epidermal growth factor and its receptor: the structure and function]

[Article in Japanese]

Gamou S, Shimizu N.

Department of Molecular Biology, Keio University School of Medicine.

Epidermal growth factor (EGF) binds to the specific membrane receptor and subsequently activates the signal transduction pathway through intrinsic tyrosine kinase activity. To elucidate the mechanism in which structural alteration of the EGF may affect functional properties including its receptor binding ability, site-directed mutagenesis has been employed. The functional significance of structural characteristics of the EGF receptor has been studied also by mutant receptor constructs in the transfected cells. Recent progress on the studies of the EGF and EGF receptor interaction are reviewed.

Publication Types:
English Abstract
Review

PMID: 1433980 [PubMed - indexed for MEDLINE]

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7: Semin Cancer Biol. 1990 Aug;1(4):277-84.


Epidermal growth factor receptor regulation and function.

Merlino GT.

Division of Cancer Biology and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

The epidermal growth factor (EGF) receptor is a transmembrane, cell-surface glycoprotein that mediates the mitogenic action of a family of ligands, including EGF and transforming growth factor alpha (TGF alpha). Perturbation of this signal transduction pathway by exposure to excess ligand, by overproduction of the normal EGF receptor, or by the presence of specific mutated forms of this receptor can result in dramatic alterations in cellular phenotype, including malignant transformation. Overstimulation of normal cells is avoided by precise control of the synthesis and degradation of EGF receptors. Regulation occurs at multiple levels, including transcriptional control. A number of DNA-binding proteins have now been identified which positively and negatively modulate EGF receptor gene transcription.

Publication Types:
Review

PMID: 2103502 [PubMed - indexed for MEDLINE]

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8: Mol Cell Endocrinol. 1990 May 7;70(3):205-16.


Structure, function and transforming potential of the epidermal growth factor receptor.

Velu TJ.

Laboratory of Cellular Oncology, National Cancer Institute, NIH, Bethesda, MD 20892.

Publication Types:
Review

PMID: 2193842 [PubMed - indexed for MEDLINE]

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9: Cytotechnology. 1990 May;3(3):279-93.


Monoclonal antibodies to epidermal growth factor receptors in studies of receptor structure and function.

Kawamoto T, Sato GH, Takahashi K, Nishi M, Taniguchi S, Sato JD.

Department of Biochemistry, Okayama University Dental School, Japan.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 1366662 [PubMed - indexed for MEDLINE]

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10: Pathobiology. 1990;58(1):3-14.


Sequential changes in epidermal growth factor receptor/ligand function in cultured rat liver epithelial cells transformed chemically in vitro.

Grisham JW, Tsao MS, Lee DC, Earp HS.

University of North Carolina, Chapel Hill.

Diploid WB rat liver epithelial cells contain abundant, rapidly internalized epidermal growth factor receptors, and respond pleiotropically to ligand binding. Signal transduction pathways downstream from the EGF receptor involve activation of elements that are both dependent on and independent of protein kinase C activation. Neoplastic transformation of wild-type WB rat liver epithelial cells by exposure to N-methyl-N'-nitro-N-nitrosoguanidine is associated with progressive alterations in the responses of affected cells to binding of EGF to EGF receptors, including heightened cell proliferation and the expression of several other phenotypic properties. Tumorigenic rat liver epithelial cells acquire the ability to express transforming growth factor-alpha (TGF-alpha), and to secrete this growth factor in a regulated and then unregulated manner. TGF-alpha expression, together with the presence of abundant EGF receptors, provides affected cells with an autocrine growth cycle. The ability of transformed WB rat liver epithelial cells to produce tumors cosegregates clonally with TGF-alpha expression and with heightened expression of c-myc, c-Ha-ras and c-Ki-ras proto-oncogenes.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 2187476 [PubMed - indexed for MEDLINE]

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11: Biofactors. 1989 Mar;2(1):11-5.


Epidermal growth factor: the receptor and its function.

Todderud G, Carpenter G.

Vanderbilt University School of Medicine, Department of Biochemistry, Nashville, TN 37232-0146.

Epidermal growth factor (EGF) is a small polypeptide hormone with mitogenic properties in vivo and in vitro. EGF elicits biologic responses by binding to a cell surface receptor which is a transmembrane glycoprotein containing a cytoplasmic protein tyrosine kinase. EGF responses are mediated by ligand binding and activation of this intrinsic protein kinase. The receptor can be phosphorylated by other protein kinases, and this may regulate receptor function. Stimulation of the receptor tyrosine kinase activity by ligand binding must regulate the activity of an as yet undefined molecule(s) responsible for transmitting a mitogenic signal to the nucleus.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 2553047 [PubMed - indexed for MEDLINE]

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12: Prog Growth Factor Res. 1989;1(1):23-32.


Structural basis for epidermal growth factor receptor function.

Hsuan JJ, Panayotou G, Waterfield MD.

Ludwig Institute for Cancer Research, London, U.K.

The receptor for epidermal growth factor (EGF) has been the subject of intense study primarily as a consequence of the pioneering studies of Cohen on growth factors and also because of its homology to the transforming protein encoded by the avian oncogene v-erbB, which is a truncated receptor and its consequent role in cancer. Although similar structural mutation of the EGF receptor has not yet been found in human tumours, aberrant overexpression of both EGF receptors and c-erbB2, a closely related putative receptor, have been found to occur in squamous cell carcinomas and glial tumours, and mammary carcinomas respectively. In addition to EGF, the related polypeptides transforming growth factor alpha (TGF alpha) and vaccinia virus growth factor are also ligands for the EGF receptor. Expression of TGF alpha occurs during embryonal development and in specific adult tissues; it may also play a role in cellular transformation These important properties, as well as the potential roles of both TGF alpha and EGF in wound repair, have emphasized the need to understand EGF receptor structure, function and regulation. This review discusses the structural properties of the EGF receptor and how these can be related to receptor function and regulation.

Publication Types:
Review

PMID: 2491253 [PubMed - indexed for MEDLINE]
 

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