Epidermal growth factor
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[[Image:MAPKpathway.png|thumb|right|Diagram showing key components of the [[MAPK/ERK pathway]]. In the diagram, "P" represents [[phosphate]]. Note EGF at the very top.]]
'''Epidermal growth factor''' or '''EGF''' is a [[growth factor]] that plays an important role in the regulation of [[cell growth]], [[proliferation]], and [[Cellular differentiation|differentiation]]. It also increases cancer risk.<ref name=Herbst/> Human EGF is a 6045-[[dalton (unit)|Da]] [[protein]] with 53 [[amino acid|amino acid residues]] and three intramolecular [[disulfide bond]]s.<ref>{{cite journal | author =Carpenter G, and Cohen S. | title =Epidermal growth factor | journal =J. Biol. Chem. | year=1990 | volume=265 | issue=14 | pages=7709–7712 | pmid = 2186024}}</ref>
==History==
The discovery of EGF won Dr. Stanly Cohen a Nobel Prize in Physiology and Medicine in 1986<ref>[http://nobelprize.org/nobel_prizes/medicine/laureates/1986/presentation-speech.html The Nobel Prize in Physiology or Medicine 1986 - Presentation Speech<!-- Bot generated title -->]</ref> and was patented for cosmetic use by Dr. Greg Brown in 1989<ref>[http://www.freepatentsonline.com/5618544.html Method of decreasing cutaneous senescence - Patent 5618544<!-- Bot generated title -->]</ref>.
==Function==
EGF results in cellular proliferation, differentiation, and survival. <ref name=Herbst> {{cite journal |author=Herbst RS |title=Review of epidermal growth factor receptor biology |journal=Int. J. Radiat. Oncol. Biol. Phys. |volume=59 |issue=2 Suppl |pages=21–6 |year=2004 |pmid=15142631 |doi=10.1016/j.ijrobp.2003.11.041}}</ref> This, in turn, results in an increased risk of [[cancer]]. <ref name=Herbst/>
==Mechanism==
EGF acts by binding with high [[affinity]] to [[epidermal growth factor receptor]] (EGFR) on the [[plasma membrane|cell surface]] and stimulating 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 [[biochemistry|biochemical]] changes within the cell - a rise in intracellular [[calcium]] levels, increased [[glycolysis]] and [[protein synthesis]], and increases in the [[gene expression|expression]] of certain [[gene]]s including the gene for EGFR - that ultimately lead to [[DNA replication|DNA synthesis]] and cell proliferation.<ref>{{cite journal | author =Fallon JH, Seroogy KB.''et al'' | title=Epidermal growth factor immunoreactive material in the central nervous system: location and development | journal =Science | year=1984 | volume=224 | issue=4653 | pages=1107–1109 | pmid = 6144184 | doi=10.1126/science.6144184}}</ref>
==EGF-family==
EGF is the founding member of the [[EGF-like domain|EGF-family of proteins]]. Members of this protein family have highly similar structural and functional characteristics. Besides EGF itself other family members include:<ref name=dreux>{{cite journal | author =Dreux AC, Lamb DJ. ''et al.'' | title =The epidermal growth factor receptors and their family of ligands: their putative role in atherogenesis | journal =Atherosclerosis | year=2006 | volume=186 | issue=1 | pages=38–53 | pmid = 16076471 | doi =10.1016/j.atherosclerosis.2005.06.038}}</ref>
*[[Heparin-binding EGF-like growth factor]] (HB-EGF)
*[[TGF alpha|transforming growth factor-α]] (TGF-α)
*[[Amphiregulin]] (AR)
*[[Epiregulin]] (EPR)
*[[Epigen]]
*[[Betacellulin]] (BTC)
*[[neuregulin-1]] (NRG1)
*[[neuregulin|neuregulin-2]] (NRG2)
*[[neuregulin|neuregulin-3]] (NRG3)
*[[neuregulin|neureguline-4]] (NRG4).
All family members contain one or more repeats of the [[conserved sequence|conserved]] amino acid sequence:
<font 16>'''[[cysteine|C]]X<sub>7</sub>[[cysteine|C]]X<sub>4-5</sub>[[cysteine|C]]X<sub>10-13</sub>[[cysteine|C]]X[[cysteine|C]]X<sub>8</sub>[[glycine|G]]X[[arginine|R]][[cysteine|C]]'''</font 16>
Where <font 16>'''X'''</font 16> represents any [[amino acid]].<ref name=dreux/>
This sequence contains 6 [[cysteine]] residues that form three intramolecular [[disulfide bond]]s. 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.<ref name=harris>{{cite journal | author =Harris RC, Chung E, and Coffey RJ. | title =EGF receptor ligands | journal =Exp. Cell. Res. | year=2003 | volume=284 | issue=1 | pages=2–13 | pmid = 12648462 | doi =10.1016/S0014-4827(02)00105-2}}</ref>
==EGF therapy==
Because of the increased risk of cancer by EGF, inhibiting it decreases cancer risk.<ref name=Herbst/> Such medications are so far mainly based on inhibiting the [[EGF receptor]]. [[Monoclonal antibodies]] and [[small-molecule inhibitors]] are potential substances for this purpose.
==References==
{{reflist}}
==External links==
*EGF at the [http://www.hprd.org/protein/00578 Human Protein Reference Database].
* {{MeshName|Epidermal+growth+factor}}
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal | author=Boonstra J, Rijken P, Humbel B, ''et al.'' |title=The epidermal growth factor |journal=Cell Biol. Int. |volume=19 |issue= 5 |pages= 413–30 |year= 1995 |pmid= 7640657 |doi=10.1006/cbir.1995.1086 }}
*{{cite journal | author=Dvorak B |title=Epidermal growth factor and necrotizing enterocolitis |journal=Clinics in perinatology |volume=31 |issue= 1 |pages= 183–92 |year= 2004 |pmid= 15183666 |doi= 10.1016/j.clp.2004.03.015 }}
*{{cite journal | author=Howell WM |title=Epidermal growth factor gene polymorphism and development of cutaneous melanoma |journal=J. Invest. Dermatol. |volume=123 |issue= 4 |pages= xx-xxi |year= 2004 |pmid= 15373802 |doi= 10.1111/j.0022-202X.2004.23308.x }}
}}
{{refend}}
{{Signaling proteins}}
{{Gastrointestinal hormones}}
[[Category:Growth factors]]
[[Category:Morphogens]]
[[de:Epidermaler Wachstumsfaktor]]
[[fr:Facteur de croissance épidermique]]
[[ja:上皮成長因子]]
[[zh:表皮生长因子]]
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