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Encyclopedia > Epidermal growth factor receptor
The extracellular domain of EGFR in a complex with EGF PDB 1NQL
Epidermal growth factor receptor
Identifiers
Symbol(s) EGFR ERBB1
Entrez 1956
OMIM 131550
RefSeq NM_005228
UniProt P00533
Other data
EC number 2.7.1.112
Locus Chr. 7 p12

Epidermal growth factor receptor (EGFR) is the receptor for epidermal growth factor (EGF). It is a member of the ErbB family receptors, a subfamily of four closely related receptor tyrosine kinases: EGFR (ErbB-1), HER2/c-neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4). Mutations affecting EGFR expression or activity could result in cancer. Image File history File links EGFR_structure. ... The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. ... Hugo is a masculine name. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The National Center for Biotechnology Information (NCBI) is part of the US National Library of Medicine (NLM), which is a branch of the US National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... Short and long arms Chromosome. ... Chromosome 7 is one of the 23 pairs of chromosomes in humans. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... Epidermal Growth Factor or EGF is a 6045 Da protein with 53 amino acid residues and three intramolecular disulfide bonds. ... Tyrosine kinases are a subclass of protein kinase, see there for the principles of protein phosphorylation A tyrosine kinase (EC 2. ... HER2/neu (also known as ErbB-2) is a member of the epidermal growth factor receptor (EGFR) family and is notable for its role in the pathogenesis of breast cancer and as a target of treatment. ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these cells to invade other tissues, either by direct growth into adjacent tissue through invasion or by implantation into distant sites by metastasis. ...

Contents

Structure


Image File history File links EGF_Receptor. ...


Function

EGFR exist on the cell surface as inactive monomers and is activated by binding of its specific ligands, including epidermal growth factor, transformation growth factor α (TGFα), neuregulin (neu)or others. On activation, EGFR can pair with another EGFR to form an active homodimer or an EGF receptor may pair with another member of the ErbB receptor family, such as Her 2/neu, to create a heterodimer. Evidence also suggests that a cluster of active EGFR can form. In chemistry, a ligand is an atom, ion, or molecule (see also: functional group) that generally donates one or more of its electrons through a coordinate covalent bond to, or shares its electrons through a covalent bond with, one or more central atoms or ions (these ligands act as a... Epidermal Growth Factor or EGF is a 6045 Da protein with 53 amino acid residues and three intramolecular disulfide bonds. ... Transforming growth factor (TGF) is one of many characterized growth factors that exist in nature. ...


The binding of the ligand stimulates the intrinsic protein-tyrosine kinase activity of EGFR which initiates a signal transduction cascade, principally involving the MAPK, Akt and JNK pathways, leading to DNA synthesis and cell proliferation[1]. The kinase activity can also result in autophosphorylation of five tyrosine residues in the C-terminal domain of EGFR. Autophosphorylation elicits downstream activation and signaling events of other proteins that are often distinct from those activated by the kinase domain of EGFR. Such proteins modulate phenotypes such as cell migration, adhesion, and proliferation. The kinase domain of EGFR can also cross-phosphorylate tyrosine residues of other receptors it is aggregated with, and can itself be activated in that manner. In biology, signal transduction is any process by which a cell converts one kind of signal or stimulus into another. ... In cell biology, mitogen-activated protein kinases (MAPKs) are serine/threonine-specific protein kinases that respond to extracellular stimuli and regulate various cellular activities, such as gene expression, mitosis, differentiation, and cell survival/apoptosis. ... Phosphoinositide 3-kinases (PI 3-kinases or PI3Ks) are a family of related enzymes that are capable of phosphorylating the 3 position hydroxyl group of the inositol ring of phosphatidylinositol (PtdIns)[1]. The various 3-phosphorylated phosphoinositides that are produced by PI 3-kinases (PtdIns3P, PtdIns(3,4)P2, PtdIns... In cell biology, mitogen-activated protein (MAP) kinases (EC 2. ... This article or section is in need of attention from an expert on the subject. ... Tyrosine (from the Greek tyros, meaning cheese, as it was first discovered in cheese), 4-hydroxyphenylalanine, or 2-amino-3(4-hydroxyphenyl)-propanoic acid, is one of the 20 amino acids that are used by cells to synthesize proteins. ... In biology, a domain (also superregnum, superkingdom, or empire) is the top-level grouping of organisms in scientific classification, higher than a kingdom. ... Cell migration is a central process in the development and maintenance of multicellular organisms. ... Dew drops adhering to a spider web Adhesion is the molecular attraction exerted between bodies in contact. ... The word proliferation can refer to: Nuclear proliferation Chemical weapon proliferation the spread in use of other weapons systems Cell proliferation According to Gloria Anzaldúa (1990), the difference between appropriation and proliferation is that the first steals and harms; the second helps heal breaches of knowledge. ...


Clinical applications

Mutations that lead to EGFR overexpression (known as upregulation) or overactivity have been associated with a number of cancers, including glioblastoma multiforme and lung cancer. In biology, mutations are changes to the genetic material (either DNA or RNA). ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these cells to invade other tissues, either by direct growth into adjacent tissue through invasion or by implantation into distant sites by metastasis. ... Image 1a. ... Lung cancer is a cancer of the lungs characterized by the presence of malignant tumours. ...


Mutations involving EGFR could lead to its constant activation which could result in uncontrolled cell division - a predisposition for cancer[2] . Consequently, mutations of EGFR have been identified in several types of cancer, and it is the target of an expanding class of anticancer therapies. This article is about mutation in biology, for other meanings see: mutation (disambiguation). ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these cells to invade other tissues, either by direct growth into adjacent tissue through invasion or by implantation into distant sites by metastasis. ...


The identification of EGFR as an oncogene has led to the development of anticancer therapeutics directed against EGFR, including gefitinib[3] and erlotinib for lung cancer, cetuximab for colon cancer, and trastuzumab for breast cancer. An oncogene is a modified gene that increases the malignancy of a tumor cell. ... Gefitinib is a new drug used in the treatment of certain types of cancer. ... Erlotinib hydrochloride (trade name Tarceva®, Genentech/OSIP) is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. ... Lung cancer is a cancer of the lungs characterized by the presence of malignant tumours. ... Cetuximab (Erbitux®) is a chimeric monoclonal antibody given by intravenous injection for treatment of colorectal cancer. ... Diagram of the stomach, colon, and rectum Colorectal cancer includes cancerous growths in the colon, rectum and appendix. ... Herceptin Logo Trastuzumab (Herceptin®) is an anti-cancer therapy that acts on the HER2/neu (erbB2) receptor. ... Breast cancer is cancer of breast tissue. ...


These therapies are based in the use of monoclonal antibodies against EGFR or in protein kinase inhibitors. The monoclonal antibodies block the extracellular ligand binding domain with the use of anti-EGFR antibodies. With the binding site blocked, signal molecules can no longer attach there and activate the tyrosine kinase. Another method is using small molecules to inhibit the EGFR tyrosine kinase. This molecule travels down the EGFR polypedptide and blocks the relay proteins from binding to the tyrosine kinase. Both methods result in inhibition of downstream components of the EGFR pathway. By halting the signaling cascade, tumor growth is stopped.


Links

  1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15142631

References

  1. a  A comprehensive pathway map of epidermal growth factor receptor signaling. Molecular Systems Biology doi:10.1038/msb4100014, 2005 May [1]
  2. a  Image:Free_text.png Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004 May 20; 350(21): 2129-39. PMID 15118073 Free text
  3. a  EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004 Jun 4; 304(5676): 1497-500. PMID 15118125

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