Epidermal growth factor

{{missing information|section|the entire 1207-aa long gene product: the pro-pre-EGF; what happens if things go wrong (renal hypomagnesemia 4, OMIM 611718)|date=December 2023}}

In humans, EGF has 53 amino acids (sequence NSDSECPLSHDGYCLHDGVCMYIEALDKYACNCVVGYIGERCzYRDLKWWELR), with a molecular mass of around 6 kDa. It contains three disulfide bridges (Cys6-Cys20, Cys14-Cys31, Cys33-Cys42).

EGF, via binding to its cognate receptor, results in cellular proliferation, differentiation, and survival.{{cite journal | vauthors = Herbst RS | title = Review of epidermal growth factor receptor biology | journal = International Journal of Radiation Oncology, Biology, Physics | volume = 59 | issue = 2 Suppl | pages = 21–6 | year = 2004 | pmid = 15142631 | doi = 10.1016/j.ijrobp.2003.11.041 | doi-access = free }}

Salivary EGF, which seems to be regulated by dietary inorganic iodine, also plays an important physiological role in the maintenance of oro-esophageal and gastric tissue integrity. The biological effects of salivary EGF include healing of oral and gastroesophageal ulcers, inhibition of gastric acid secretion, stimulation of DNA synthesis as well as mucosal protection from intraluminal injurious factors such as gastric acid, bile acids, pepsin, and trypsin and to physical, chemical and bacterial agents.{{cite journal | vauthors = Venturi S, Venturi M | title = Iodine in evolution of salivary glands and in oral health | journal = Nutrition and Health | volume = 20 | issue = 2 | pages = 119–34 | year = 2009 | pmid = 19835108 | doi = 10.1177/026010600902000204 | s2cid = 25710052 }}

The Epidermal growth factor can be found in platelets, urine, saliva, milk, tears, and blood plasma.{{cite book | vauthors = Kumar V, Abbas AK, Fausto N, Robbins SL, Cotran RS | title = Robbins and Cotran pathologic basis of disease | edition = 7th | publisher = Elsevier Saunders | location = St. Louis, Mo | year = 2005 | isbn = 978-0-7216-0187-8 }} It can also be found in the submandibular glands,{{Citation| vauthors = Chao J |title=Chapter 624 - Mouse Kallikrein 9, Epidermal Growth Factor-binding Protein|date=2013-01-01 |work=Handbook of Proteolytic Enzymes | edition = Third |pages=2830–2831| veditors = Rawlings ND, Salvesen G |publisher=Academic Press |doi=10.1016/b978-0-12-382219-2.00624-4|isbn=978-0-12-382219-2}} and the parotid gland. The production of EGF has been found to be stimulated by testosterone.{{Citation needed|date=November 2020}}

{{Split section portions|Growth factor|date=August 2022}}

Polypeptide growth factors include:{{cite book|title=Biochemistry| vauthors = Satyanarayana U |date=2002|publisher=Books and Allied|isbn=8187134801|edition=2nd|location=Kolkata, India|oclc=71209231}}

File:MAPKpathway diagram.svg. In the diagram, "P" represents phosphate. Note EGF at the very top.]]

EGF acts by binding with high affinity to epidermal growth factor receptor (EGFR) on the cell surface. This stimulates ligand-induced dimerization,{{cite journal | vauthors = Dawson JP, Berger MB, Lin CC, Schlessinger J, Lemmon MA, Ferguson KM | title = Epidermal growth factor receptor dimerization and activation require ligand-induced conformational changes in the dimer interface | journal = Molecular and Cellular Biology | volume = 25 | issue = 17 | pages = 7734–42 | date = September 2005 | pmid = 16107719 | pmc = 1190273 | doi = 10.1128/MCB.25.17.7734-7742.2005 }} activating the intrinsic protein-tyrosine kinase activity of the receptor (see the second diagram). The tyrosine kinase activity, in turn, initiates a signal transduction cascade that results in a variety of biochemical changes within the cell – a rise in intracellular calcium levels, increased glycolysis and protein synthesis, and increases in the expression of certain genes including the gene for EGFR – that ultimately lead to DNA synthesis and cell proliferation.{{cite journal | vauthors = Fallon JH, Seroogy KB, Loughlin SE, Morrison RS, Bradshaw RA, Knaver DJ, Cunningham DD | title = Epidermal growth factor immunoreactive material in the central nervous system: location and development | journal = Science | volume = 224 | issue = 4653 | pages = 1107–9 | date = June 1984 | pmid = 6144184 | doi = 10.1126/science.6144184 | bibcode = 1984Sci...224.1107F }}

{{main|EGF-like domain}}

EGF is the founding member of the EGF-family of proteins. Members of this protein family have highly similar structural and functional characteristics. Besides EGF itself other family members include:{{cite journal | vauthors = Dreux AC, Lamb DJ, Modjtahedi H, Ferns GA | title = The epidermal growth factor receptors and their family of ligands: their putative role in atherogenesis | journal = Atherosclerosis | volume = 186 | issue = 1 | pages = 38–53 | date = May 2006 | pmid = 16076471 | doi = 10.1016/j.atherosclerosis.2005.06.038 }}

• Heparin-binding EGF-like growth factor (HB-EGF)
• transforming growth factor-α (TGF-α)
• Amphiregulin (AR)
• Epiregulin (EPR)
• Epigen
• Betacellulin (BTC)
• neuregulin-1 (NRG1)
• neuregulin-2 (NRG2)
• neuregulin-3 (NRG3)
• neuregulin-4 (NRG4).

All family members contain one or more repeats of the conserved amino acid sequence:

CX₇CX_4-5CX_10-13CXCX₈GXRC

Where C is cysteine, G is glycine, R is arginine, and X represents any amino acid.

This sequence contains six cysteine residues that form three intramolecular disulfide bonds. Disulfide bond formation generates three structural loops that are essential for high-affinity binding between members of the EGF-family and their cell-surface receptors.

Epidermal growth factor has been shown to interact with epidermal growth factor receptors.{{cite journal | vauthors = Stortelers C, Souriau C, van Liempt E, van de Poll ML, van Zoelen EJ | title = Role of the N-terminus of epidermal growth factor in ErbB-2/ErbB-3 binding studied by phage display | journal = Biochemistry | volume = 41 | issue = 27 | pages = 8732–41 | date = July 2002 | pmid = 12093292 | doi = 10.1021/bi025878c }}{{cite journal | vauthors = Wong L, Deb TB, Thompson SA, Wells A, Johnson GR | title = A differential requirement for the COOH-terminal region of the epidermal growth factor (EGF) receptor in amphiregulin and EGF mitogenic signaling | journal = The Journal of Biological Chemistry | volume = 274 | issue = 13 | pages = 8900–9 | date = March 1999 | pmid = 10085134 | doi = 10.1074/jbc.274.13.8900 | doi-access = free }}

Recombinant human epidermal growth factor, sold under the brand name Heberprot-P, is used to treat diabetic foot ulcers. It can be given by injection into the wound site,{{cite journal | vauthors = Berlanga J, Fernández JI, López E, López PA, del Río A, Valenzuela C, Baldomero J, Muzio V, Raíces M, Silva R, Acevedo BE, Herrera L | title = Heberprot-P: a novel product for treating advanced diabetic foot ulcer | journal = MEDICC Review | volume = 15 | issue = 1 | pages = 11–5 | date = January 2013 | pmid = 23396236 | doi = 10.1590/s1555-79602013000100004 | doi-access = free }} or may be used topically.{{cite journal | vauthors = Yang S, Geng Z, Ma K, Sun X, Fu X | title = Efficacy of Topical Recombinant Human Epidermal Growth Factor for Treatment of Diabetic Foot Ulcer: A Systematic Review and Meta-Analysis | journal = The International Journal of Lower Extremity Wounds | volume = 15 | issue = 2 | pages = 120–5 | date = June 2016 | pmid = 27151755 | doi = 10.1177/1534734616645444 | s2cid = 43897291 }} Tentative evidence shows improved wound healing.{{cite journal | vauthors = Martí-Carvajal AJ, Gluud C, Nicola S, Simancas-Racines D, Reveiz L, Oliva P, Cedeño-Taborda J | title = Growth factors for treating diabetic foot ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 10 | pages = CD008548 | date = October 2015 | pmid = 26509249 | doi = 10.1002/14651858.CD008548.pub2 | pmc = 8665376 }} Safety has been poorly studied.

EGF is used to modify synthetic scaffolds for manufacturing of bioengineered grafts by emulsion electrospinning or surface modification methods.{{cite journal | vauthors = Haddad T, Noel S, Liberelle B, El Ayoubi R, Ajji A, De Crescenzo G | title = Fabrication and surface modification of poly lactic acid (PLA) scaffolds with epidermal growth factor for neural tissue engineering | journal = Biomatter | volume = 6 | issue = 1 | pages = e1231276 | date = January 2016 | pmid = 27740881 | pmc = 5098722 | doi = 10.1080/21592535.2016.1231276 }}{{cite journal| vauthors = Tenchurin T, Lyundup A, Demchenko A, Krasheninnikov M, Balyasin M, Klabukov I, Shepelev AD, Mamagulashvili VG, Orehov AS |date=2017|title=Modification of biodegradable fibrous scaffolds with Epidermal Growth Factor by emulsion electrospinning for promotion of epithelial cells proliferation|url=https://zenodo.org/record/1175806|journal=Гены и клетки |language=ru|volume=12|issue=4|pages=47–52|doi=10.23868/201707029|s2cid=90593089 }}

EGF plays an enhancer role on the osteogenic differentiation of dental pulp stem cells (DPSCs) because it is capable of increasing extracellular matrix mineralization. A low concentration of EGF (10 ng/ml) is sufficient to induce morphological and phenotypic changes. These data suggests that DPSCs in combination with EGF could be an effective stem cell-based therapy to bone tissue engineering applications in periodontics and oral implantology.{{cite journal | vauthors = Del Angel-Mosqueda C, Gutiérrez-Puente Y, López-Lozano AP, Romero-Zavaleta RE, Mendiola-Jiménez A, Medina-De la Garza CE, Márquez-M M, De la Garza-Ramos MA | title = Epidermal growth factor enhances osteogenic differentiation of dental pulp stem cells in vitro | journal = Head & Face Medicine | volume = 11 | pages = 29 | date = September 2015 | pmid = 26334535 | pmc = 4558932 | doi = 10.1186/s13005-015-0086-5 | doi-access = free }}

EGF was the second growth factor to be identified.{{cite book | vauthors = Pache JC | chapter=Epidermal growth factors |date=2006-01-01|chapter-url=http://www.sciencedirect.com/science/article/pii/B0123708796001381| title = Encyclopedia of Respiratory Medicine|pages=129–133| veditors = Laurent GJ, Shapiro SD |place=Oxford|publisher=Academic Press|language=en|doi=10.1016/b0-12-370879-6/00138-1|isbn=978-0-12-370879-3|access-date=2020-11-30 }} Initially, human EGF was known as urogastrone. Stanley Cohen discovered EGF while working with Rita Levi-Montalcini at the Washington University in St. Louis during experiments researching nerve growth factor. For these discoveries Levi-Montalcini and Cohen were awarded the 1986 Nobel Prize in Physiology or Medicine.

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• {{cite journal | vauthors = Boonstra J, Rijken P, Humbel B, Cremers F, Verkleij A, van Bergen en Henegouwen P | title = The epidermal growth factor | journal = Cell Biology International | volume = 19 | issue = 5 | pages = 413–30 | date = May 1995 | pmid = 7640657 | doi = 10.1006/cbir.1995.1086 | s2cid = 20186286 }}
• {{cite journal | vauthors = Dvorak B | title = Epidermal growth factor and necrotizing enterocolitis | journal = Clinics in Perinatology | volume = 31 | issue = 1 | pages = 183–92 | date = March 2004 | pmid = 15183666 | doi = 10.1016/j.clp.2004.03.015 }}
• {{cite journal | vauthors = Howell WM | title = Epidermal growth factor gene polymorphism and development of cutaneous melanoma | journal = The Journal of Investigative Dermatology | volume = 123 | issue = 4 | pages = xx–xxi | date = October 2004 | pmid = 15373802 | doi = 10.1111/j.0022-202X.2004.23308.x | doi-access = free }}

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{{Commons category|Epidermal growth factor, EGF}}

• [http://www.zbfarm.com Shaanxi Zhongbang Pharma-Tech Co., Ltd.-Supply of Epidermal Growth Factor]
• EGF at the [http://www.hprd.org/protein/00578 Human Protein Reference Database] {{Webarchive|url=https://web.archive.org/web/20050503115213/http://www.hprd.org/protein/00578 |date=2005-05-03 }}.
• {{MeshName|Epidermal+growth+factor}}
• [http://www.ebi.ac.uk/biomodels-main/static-pages.do?page=ModelMonth%252FAugust2006%2FBIOMD0000000048_MM EGF model in BioModels database]

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{{Signaling proteins}}

{{Gastrointestinal hormones}}

{{Growth factor receptor modulators}}

Category:Growth factors

Category:Morphogens