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{{short description|Protein that stimulates cell division and differentiation}}
{{short description|Protein that stimulates cell division and differentiation}}
{{Distinguish|EF-G}}
{{Distinguish|EF-G|VEGF}}
{{Redirect|URG}}
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{{Infobox_gene}}
{{Infobox_gene}}


'''Epidermal growth factor''' ('''EGF''') is a [[protein]] that stimulates [[cell growth]] and [[Cellular differentiation|differentiation]] by binding to its receptor, [[Epidermal growth factor receptor|EGFR]]. [[Human]] EGF is 6-k[[dalton (unit)|Da]]<ref name="pmid12648462">{{cite journal | vauthors = Harris RC, Chung E, Coffey RJ | title = EGF receptor ligands | journal = Experimental Cell Research | volume = 284 | issue = 1 | pages = 2–13 | date = March 2003 | pmid = 12648462 | doi = 10.1016/S0014-4827(02)00105-2 }}</ref> and has 53 [[amino acid|amino acid residues]] and three intramolecular [[disulfide bond]]s.<ref name="pmid2186024">{{cite journal | vauthors = Carpenter G, Cohen S | title = Epidermal growth factor | journal = The Journal of Biological Chemistry | volume = 265 | issue = 14 | pages = 7709–12 | date = May 1990 | pmid = 2186024 | doi = | url = http://www.jbc.org/cgi/reprint/265/14/7709 }}</ref>
'''Epidermal growth factor''' ('''EGF''') is a [[protein]] that stimulates [[cell growth]] and [[Cellular differentiation|differentiation]] by binding to its receptor, [[Epidermal growth factor receptor|EGFR]]. [[Human]] EGF is 6-k[[dalton (unit)|Da]]<ref name="pmid12648462">{{cite journal | vauthors = Harris RC, Chung E, Coffey RJ | title = EGF receptor ligands | journal = Experimental Cell Research | volume = 284 | issue = 1 | pages = 2–13 | date = March 2003 | pmid = 12648462 | doi = 10.1016/S0014-4827(02)00105-2 }}</ref> and has 53 [[amino acid|amino acid residues]] and three intramolecular [[disulfide bond]]s.<ref name="pmid2186024">{{cite journal | vauthors = Carpenter G, Cohen S | title = Epidermal growth factor | journal = The Journal of Biological Chemistry | volume = 265 | issue = 14 | pages = 7709–12 | date = May 1990 | doi = 10.1016/S0021-9258(19)38983-5 | pmid = 2186024 | doi-access = free }}</ref>


EGF was originally described as a secreted peptide found in the [[submaxillary gland]]s of [[Mus musculus|mice]] and in human [[urine]]. EGF has since been found in many human tissues, including [[submandibular gland]] (submaxillary gland),<ref name="Venturi2009" /> and [[parotid gland]].<ref name=Venturi2009/> Initially, human EGF was known as '''urogastrone'''.<ref name=":0">{{cite journal | vauthors = Hollenberg MD, Gregory H | title = Epidermal growth factor-urogastrone: biological activity and receptor binding of derivatives | journal = Molecular Pharmacology | volume = 17 | issue = 3 | pages = 314–20 | date = May 1980 | pmid = 6248761 | url = http://molpharm.aspetjournals.org/content/17/3/314 }}</ref>
EGF was originally described as a secreted peptide found in the [[submaxillary gland]]s of [[Mus musculus|mice]] and in human [[urine]]. EGF has since been found in many human tissues, including [[Platelet|platelets]],<ref name="Custo">{{cite journal | vauthors = Custo S, Baron B, Felice A, Seria E | title = A comparative profile of total protein and six angiogenically-active growth factors in three platelet products | journal = GMS Interdisciplinary Plastic and Reconstructive Surgery DGPW | volume = 11 | issue = Doc06 | pages = Doc06 | date = 5 July 2022 | pmid = 35909816 | pmc = 9284722 | doi = 10.3205/iprs000167 }}</ref> [[submandibular gland]] (submaxillary gland),<ref name="Venturi2009" /> and [[parotid gland]].<ref name=Venturi2009/> Initially, human EGF was known as '''urogastrone'''.<ref name=":0">{{cite journal | vauthors = Hollenberg MD, Gregory H | title = Epidermal growth factor-urogastrone: biological activity and receptor binding of derivatives | journal = Molecular Pharmacology | volume = 17 | issue = 3 | pages = 314–320 | date = May 1980 | pmid = 6248761 | url = http://molpharm.aspetjournals.org/content/17/3/314 }}</ref>


== Structure ==
== Structure ==
{{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 [[Human|humans]], EGF has 53 [[Amino acid|amino acids]],<ref name="pmid2186024" /> with a [[molecular mass]] of around 6 [[kDa]].<ref name="pmid12648462" /> It contains three [[Disulfide|disulfide bridges]].<ref name="pmid2186024" />
In [[Human|humans]], EGF has 53 [[Amino acid|amino acids]] (sequence NSDSECPLSHDGYCLHDGVCMYIEALDKYACNCVVGYIGERCzYRDLKWWELR),<ref name="pmid2186024" /> with a [[molecular mass]] of around 6 [[kDa]].<ref name="pmid12648462" /> It contains three [[Disulfide|disulfide bridges]] (Cys6-Cys20, Cys14-Cys31, Cys33-Cys42).<ref name="pmid2186024" />


== Function ==
== Function ==
EGF, via binding to [[Epidermal growth factor receptor|its cognate receptor]], results in cellular proliferation, differentiation, and survival.<ref name="Herbst">{{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 }}</ref>
EGF, via binding to [[Epidermal growth factor receptor|its cognate receptor]], results in cellular proliferation, differentiation, and survival.<ref name="Herbst">{{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 }}</ref>


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.<ref name=Venturi2009>{{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 }}</ref>
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.<ref name=Venturi2009>{{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 }}</ref>


== Biological sources ==
== Biological sources ==
Epidermal growth factor can be found in [[urine]], [[saliva]], [[milk]], [[tears]], and [[blood plasma]].<ref name="isbn0-7216-0187-1">{{cite book | first1 = Vinay | last1 = Kumar | first2 = Abul K | last2 = Abbas | first3 = Nelson | last3 = Fausto | first4 = Stanley L | last4 = Robbins | first5 = Ramzi S | last5 = Cotran | name-list-style = vanc | 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 }}</ref> It can also be found in the [[Submandibular gland|submandibular glands]],<ref name="Venturi2009" /><ref name=":1">{{Citation|last=Chao|first=Julie|title=Chapter 624 - Mouse Kallikrein 9, Epidermal Growth Factor-binding Protein|date=2013-01-01|url=http://www.sciencedirect.com/science/article/pii/B9780123822192006244|work=Handbook of Proteolytic Enzymes (Third Edition)|pages=2830–2831|editor-last=Rawlings|editor-first=Neil D.|publisher=Academic Press|language=en|doi=10.1016/b978-0-12-382219-2.00624-4|isbn=978-0-12-382219-2|access-date=2020-11-30|editor2-last=Salvesen|editor2-first=Guy}}</ref> and the [[parotid gland]].<ref name="Venturi2009" /><ref name=":1" /> The production of EGF has been found to be stimulated by [[testosterone]].{{Citation needed|date=November 2020}}
The Epidermal growth factor can be found in [[Platelet|platelets]],<ref name="Custo" /> [[urine]], [[saliva]], [[milk]], [[tears]], and [[blood plasma]].<ref name="isbn0-7216-0187-1">{{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 }}</ref> It can also be found in the [[Submandibular gland|submandibular glands]],<ref name="Venturi2009" /><ref name=":1">{{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}}</ref> and the [[parotid gland]].<ref name="Venturi2009" /><ref name=":1" /> The production of EGF has been found to be stimulated by [[testosterone]].{{Citation needed|date=November 2020}}

== Polypeptide growth factors ==
{{Split section portions|Growth factor|date=August 2022}}
⚫
Polypeptide growth factors include:<ref>{{cite book|title=Biochemistry| vauthors = Satyanarayana U |date=2002|publisher=Books and Allied|isbn=8187134801|edition=2nd|location=Kolkata, India|oclc=71209231}}</ref>


⚫
== Selected Polypeptide Growth Factors<ref>{{Cite book|title=Biochemistry|last=Satyanarayana, U.|date=2002|publisher=Books and Allied|isbn=8187134801|edition=2nd|location=Kolkata, India|oclc=71209231}}</ref> ==
{| class="wikitable"
{| class="wikitable"
|+
|+
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|-
|-
|1
|1
|Epidermal growth factor
|Epidermal growth factor (EGF)
|Salivary gland
|Salivary gland
|Stimulate growth of epidermal and epithelial cell
|Stimulates growth of epidermal and epithelial cells
|-
|-
|2
|2
|Platelet derived growth factor
|[[Platelet derived growth factor]]
|Platelets
|Platelets
|Stimulate growth of mesenchymal cells, promotes wound healing
|Stimulates growth of mesenchymal cells, promotes wound healing
|-
|-
|3
|3
|Transforming growth factor (Alpha)
|[[TGF alpha|Transforming growth factor-alpha (TGF-α)]]
|Epithelial cell
|Epithelial cell
|Similar to Epidermal growth factor
|Similar to EGF
|-
|-
|4
|4
|Transforming growth factor (Beta)
|[[TGF beta|Transforming growth factor-beta (TGF-β)]]
|Platelets, Kidney, Placenta
|Platelets, Kidney, Placenta
|Inhibitory effect on cultures tumor cell
|Inhibitory effect on cultures tumor cell
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|Erythropoietin
|Erythropoietin
|Kidney
|Kidney
|Stimulate development of erythropoietic cells
|Stimulates development of erythropoietic cells
|-
|-
|6
|6
|Nerve growth factor (NGF)
|[[Nerve growth factor|Nerve growth factor (NGF)]]
|Salivary gland
|Salivary gland
|Stimulate the growth of sensory nerve
|Stimulates the growth of sensory nerves
|-
|-
|7
|7
|Insulin like growth factor
|[[Insulin-like growth factor]]
|Serum
|Serum
|Stimulate incorporation of sulfates into cartilage, exerts insulin like action on certain cell
|Stimulates incorporation of sulfates into cartilage, exerts insulin-like action on certain cells
|-
|-
|8
|8
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|Interleukin-1
|Interleukin-1
|Monocytes, Leukocytes
|Monocytes, Leukocytes
|Stimulate synthesis of IL-2
|Stimulates synthesis of IL-2
|-
|-
|10
|10
|Interleukin-2
|Interleukin-2
|Lymphocytes
|Lymphocytes
|Stimulate growth and maturation of T-cells
|Stimulates growth and maturation of T-cells
|}
|}

<br />
== Mechanism ==
== Mechanism ==
[[File:MAPKpathway diagram.svg|thumb|left|Diagram showing key components of the [[MAPK/ERK pathway]]. In the diagram, "P" represents [[phosphate]]. Note EGF at the very top.]]
[[File:MAPKpathway diagram.svg|thumb|left|Diagram showing key components of the [[MAPK/ERK pathway]]. In the diagram, "P" represents [[phosphate]]. Note EGF at the very top.]]
EGF acts by binding with high [[Affinity (pharmacology)|affinity]] to [[epidermal growth factor receptor]] (EGFR) on the [[plasma membrane|cell surface]]. This stimulates ligand-induced dimerization,<ref name="pmid16107719">{{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 }}</ref> 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 [[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 name="pmid6144184">{{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 }}</ref>
EGF acts by binding with high [[Affinity (pharmacology)|affinity]] to [[epidermal growth factor receptor]] (EGFR) on the [[plasma membrane|cell surface]]. This stimulates ligand-induced dimerization,<ref name="pmid16107719">{{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 }}</ref> 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 [[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 name="pmid6144184">{{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 }}</ref>


== EGF-family / EGF-like domain ==
== EGF-family / EGF-like domain ==
{{main|EGF-like domain}}
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 | 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 }}</ref>
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 | 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 }}</ref>
*[[Heparin-binding EGF-like growth factor]] (HB-EGF)
*[[Heparin-binding EGF-like growth factor]] (HB-EGF)
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== Interactions ==
== Interactions ==
⚫
Epidermal growth factor has been shown to [[Protein-protein interaction|interact]] with [[epidermal growth factor receptor|epidermal growth factor receptors]].<ref name="pmid12093292">{{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 }}</ref><ref name="pmid10085134">{{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 }}</ref>

⚫
Epidermal growth factor has been shown to [[Protein-protein interaction|interact]] with [[epidermal growth factor receptor]].<ref name="pmid12093292">{{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 }}</ref><ref name="pmid10085134">{{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 }}</ref>


==Medical uses==
==Medical uses==
[[Recombinant protein|Recombinant]] human epidermal growth factor, sold under the brand name Heberprot-P, is used to treat [[diabetic foot ulcer]]s. It can be given by injection into the wound site,<ref name=Ber2013>{{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 }}</ref> or may be used topically.<ref>{{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 }}</ref> Tentative evidence shows improved wound healing.<ref name=Mar2015>{{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 = 10 | issue = 10 | pages = CD008548 | date = October 2015 | pmid = 26509249 | doi = 10.1002/14651858.CD008548.pub2 }}</ref> Safety has been poorly studied.<ref name=Mar2015/>
[[Recombinant protein|Recombinant]] human epidermal growth factor, sold under the brand name [[Heberprot-P]], is used to treat [[diabetic foot ulcer]]s. It can be given by injection into the wound site,<ref name=Ber2013>{{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 }}</ref> or may be used topically.<ref>{{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 }}</ref> Tentative evidence shows improved wound healing.<ref name=Mar2015>{{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 }}</ref> Safety has been poorly studied.<ref name=Mar2015/>


EGF is used to modify synthetic scaffolds for manufacturing of [[Biological engineering|bioengineered]] grafts by emulsion [[electrospinning]] or surface modification methods.<ref>{{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 }}</ref><ref>{{Cite journal|last1=Tenchurin|first1=T.H.|last2=Lyundup|first2=A.V.|last3=Demchenko|first3=A.G.|last4=Krasheninnikov|first4=M.E.|last5=Balyasin|first5=M.V.|last6=Klabukov|first6=I.D.|last7=Shepelev|first7=A.D.|last8=Mamagulashvili|first8=V.G.|last9=Orehov|first9=A.S.|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|via=}}</ref>
EGF is used to modify synthetic scaffolds for manufacturing of [[Biological engineering|bioengineered]] grafts by emulsion [[electrospinning]] or surface modification methods.<ref>{{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 }}</ref><ref>{{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 }}</ref>


=== Bone regeneration ===
=== Bone regeneration ===
EGF plays an enhancer role on 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|oral implantology]].<ref>{{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 }}</ref>
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|oral implantology]].<ref>{{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 }}</ref>


== History ==
== History ==
EGF was the first [[growth factor]] to be identified.<ref>{{Citation|last=Pache|first=J. C.|title=EPIDERMAL GROWTH FACTORS|date=2006-01-01|url=http://www.sciencedirect.com/science/article/pii/B0123708796001381|work=Encyclopedia of Respiratory Medicine|pages=129–133|editor-last=Laurent|editor-first=Geoffrey J.|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|editor2-last=Shapiro|editor2-first=Steven D.}}</ref> Initially, human EGF was known as '''urogastrone'''.<ref name=":0" />
EGF was the second [[growth factor]] to be identified.<ref>{{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 }}</ref> Initially, human EGF was known as '''urogastrone'''.<ref name=":0" /> [[Stanley Cohen (biochemist)|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]].


== References ==
== References ==
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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 = 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 = 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 }}
* {{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 }}
{{refend}}
{{refend}}


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{{Commons category|Epidermal growth factor, EGF}}
{{Commons category|Epidermal growth factor, EGF}}
* [http://www.zbfarm.com Shaanxi Zhongbang Pharma-Tech Co., Ltd.-Supply of Epidermal Growth Factor]
* [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].
* 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}}
* {{MeshName|Epidermal+growth+factor}}
* [http://www.ebi.ac.uk/biomodels-main/static-pages.do?page=ModelMonth%252FAugust2006%2FBIOMD0000000048_MM EGF model in BioModels database]
* [http://www.ebi.ac.uk/biomodels-main/static-pages.do?page=ModelMonth%252FAugust2006%2FBIOMD0000000048_MM EGF model in BioModels database]

Latest revision as of 22:30, 15 October 2024

Not to be confused with EF-G or VEGF.
"URG" redirects here. For other uses, see URG (disambiguation).

EGF
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesEGF, HOMG4, URG, epidermal growth factor, epithelial growth factor
External IDsOMIM: 131530; MGI: 95290; HomoloGene: 1483; GeneCards: EGF; OMA:EGF - orthologs
Orthologs
SpeciesHumanMouse
Entrez

1950

13645

Ensembl

ENSG00000138798

ENSMUSG00000028017

UniProt

P01133

P01132

RefSeq (mRNA)

NM_001178130
NM_001178131
NM_001963
NM_001357021

NM_010113
NM_001310737
NM_001329594

RefSeq (protein)

NP_001171601
NP_001171602
NP_001954
NP_001343950

NP_001297666
NP_001316523
NP_034243

Location (UCSC)Chr 4: 109.91 – 110.01 MbChr 3: 129.47 – 129.55 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Epidermal growth factor (EGF) is a protein that stimulates cell growth and differentiation by binding to its receptor, EGFR. Human EGF is 6-kDa[5] and has 53 amino acid residues and three intramolecular disulfide bonds.[6]

EGF was originally described as a secreted peptide found in the submaxillary glands of mice and in human urine. EGF has since been found in many human tissues, including platelets,[7] submandibular gland (submaxillary gland),[8] and parotid gland.[8] Initially, human EGF was known as urogastrone.[9]

Structure

[edit]

In humans, EGF has 53 amino acids (sequence NSDSECPLSHDGYCLHDGVCMYIEALDKYACNCVVGYIGERCzYRDLKWWELR),[6] with a molecular mass of around 6 kDa.[5] It contains three disulfide bridges (Cys6-Cys20, Cys14-Cys31, Cys33-Cys42).[6]

Function

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EGF, via binding to its cognate receptor, results in cellular proliferation, differentiation, and survival.[10]

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.[8]

Biological sources

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The Epidermal growth factor can be found in platelets,[7] urine, saliva, milk, tears, and blood plasma.[11] It can also be found in the submandibular glands,[8][12] and the parotid gland.[8][12] The production of EGF has been found to be stimulated by testosterone.[citation needed]

Polypeptide growth factors

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Polypeptide growth factors include:[13]

Sr.No Growth factor Source Major function
1 Epidermal growth factor (EGF) Salivary gland Stimulates growth of epidermal and epithelial cells
2 Platelet derived growth factor Platelets Stimulates growth of mesenchymal cells, promotes wound healing
3 Transforming growth factor-alpha (TGF-α) Epithelial cell Similar to EGF
4 Transforming growth factor-beta (TGF-β) Platelets, Kidney, Placenta Inhibitory effect on cultures tumor cell
5 Erythropoietin Kidney Stimulates development of erythropoietic cells
6 Nerve growth factor (NGF) Salivary gland Stimulates the growth of sensory nerves
7 Insulin-like growth factor Serum Stimulates incorporation of sulfates into cartilage, exerts insulin-like action on certain cells
8 Tumor necrosis factor Monocytes Necrosis of tumor cells
9 Interleukin-1 Monocytes, Leukocytes Stimulates synthesis of IL-2
10 Interleukin-2 Lymphocytes Stimulates growth and maturation of T-cells

Mechanism

[edit]
Diagram showing key components of the MAPK/ERK pathway. 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,[14] 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.[15]

EGF-family / EGF-like domain

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Main article: 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:[16]

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

CX7CX4-5CX10-13CXCX8GXRC

Where C is cysteine, G is glycine, R is arginine, and X represents any amino acid.[16]

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.[5]

Interactions

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Epidermal growth factor has been shown to interact with epidermal growth factor receptors.[17][18]

Medical uses

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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,[19] or may be used topically.[20] Tentative evidence shows improved wound healing.[21] Safety has been poorly studied.[21]

EGF is used to modify synthetic scaffolds for manufacturing of bioengineered grafts by emulsion electrospinning or surface modification methods.[22][23]

Bone regeneration

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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.[24]

History

[edit]

EGF was the second growth factor to be identified.[25] Initially, human EGF was known as urogastrone.[9] 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.

References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000138798 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028017 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c Harris RC, Chung E, Coffey RJ (March 2003). "EGF receptor ligands". Experimental Cell Research. 284 (1): 2–13. doi:10.1016/S0014-4827(02)00105-2. PMID 12648462.
  6. ^ a b c Carpenter G, Cohen S (May 1990). "Epidermal growth factor". The Journal of Biological Chemistry. 265 (14): 7709–12. doi:10.1016/S0021-9258(19)38983-5. PMID 2186024.
  7. ^ a b Custo S, Baron B, Felice A, Seria E (5 July 2022). "A comparative profile of total protein and six angiogenically-active growth factors in three platelet products". GMS Interdisciplinary Plastic and Reconstructive Surgery DGPW. 11 (Doc06): Doc06. doi:10.3205/iprs000167. PMC 9284722. PMID 35909816.
  8. ^ a b c d e Venturi S, Venturi M (2009). "Iodine in evolution of salivary glands and in oral health". Nutrition and Health. 20 (2): 119–34. doi:10.1177/026010600902000204. PMID 19835108. S2CID 25710052.
  9. ^ a b Hollenberg MD, Gregory H (May 1980). "Epidermal growth factor-urogastrone: biological activity and receptor binding of derivatives". Molecular Pharmacology. 17 (3): 314–320. PMID 6248761.
  10. ^ Herbst RS (2004). "Review of epidermal growth factor receptor biology". International Journal of Radiation Oncology, Biology, Physics. 59 (2 Suppl): 21–6. doi:10.1016/j.ijrobp.2003.11.041. PMID 15142631.
  11. ^ Kumar V, Abbas AK, Fausto N, Robbins SL, Cotran RS (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. ISBN 978-0-7216-0187-8.
  12. ^ a b Chao J (2013-01-01), Rawlings ND, Salvesen G (eds.), "Chapter 624 - Mouse Kallikrein 9, Epidermal Growth Factor-binding Protein", Handbook of Proteolytic Enzymes (Third ed.), Academic Press, pp. 2830–2831, doi:10.1016/b978-0-12-382219-2.00624-4, ISBN 978-0-12-382219-2
  13. ^ Satyanarayana U (2002). Biochemistry (2nd ed.). Kolkata, India: Books and Allied. ISBN 8187134801. OCLC 71209231.
  14. ^ Dawson JP, Berger MB, Lin CC, Schlessinger J, Lemmon MA, Ferguson KM (September 2005). "Epidermal growth factor receptor dimerization and activation require ligand-induced conformational changes in the dimer interface". Molecular and Cellular Biology. 25 (17): 7734–42. doi:10.1128/MCB.25.17.7734-7742.2005. PMC 1190273. PMID 16107719.
  15. ^ Fallon JH, Seroogy KB, Loughlin SE, Morrison RS, Bradshaw RA, Knaver DJ, et al. (June 1984). "Epidermal growth factor immunoreactive material in the central nervous system: location and development". Science. 224 (4653): 1107–9. Bibcode:1984Sci...224.1107F. doi:10.1126/science.6144184. PMID 6144184.
  16. ^ a b Dreux AC, Lamb DJ, Modjtahedi H, Ferns GA (May 2006). "The epidermal growth factor receptors and their family of ligands: their putative role in atherogenesis". Atherosclerosis. 186 (1): 38–53. doi:10.1016/j.atherosclerosis.2005.06.038. PMID 16076471.
  17. ^ Stortelers C, Souriau C, van Liempt E, van de Poll ML, van Zoelen EJ (July 2002). "Role of the N-terminus of epidermal growth factor in ErbB-2/ErbB-3 binding studied by phage display". Biochemistry. 41 (27): 8732–41. doi:10.1021/bi025878c. PMID 12093292.
  18. ^ Wong L, Deb TB, Thompson SA, Wells A, Johnson GR (March 1999). "A differential requirement for the COOH-terminal region of the epidermal growth factor (EGF) receptor in amphiregulin and EGF mitogenic signaling". The Journal of Biological Chemistry. 274 (13): 8900–9. doi:10.1074/jbc.274.13.8900. PMID 10085134.
  19. ^ Berlanga J, Fernández JI, López E, López PA, del Río A, Valenzuela C, et al. (January 2013). "Heberprot-P: a novel product for treating advanced diabetic foot ulcer". MEDICC Review. 15 (1): 11–5. doi:10.1590/s1555-79602013000100004. PMID 23396236.
  20. ^ Yang S, Geng Z, Ma K, Sun X, Fu X (June 2016). "Efficacy of Topical Recombinant Human Epidermal Growth Factor for Treatment of Diabetic Foot Ulcer: A Systematic Review and Meta-Analysis". The International Journal of Lower Extremity Wounds. 15 (2): 120–5. doi:10.1177/1534734616645444. PMID 27151755. S2CID 43897291.
  21. ^ a b Martí-Carvajal AJ, Gluud C, Nicola S, Simancas-Racines D, Reveiz L, Oliva P, et al. (October 2015). "Growth factors for treating diabetic foot ulcers". The Cochrane Database of Systematic Reviews. 2015 (10): CD008548. doi:10.1002/14651858.CD008548.pub2. PMC 8665376. PMID 26509249.
  22. ^ Haddad T, Noel S, Liberelle B, El Ayoubi R, Ajji A, De Crescenzo G (January 2016). "Fabrication and surface modification of poly lactic acid (PLA) scaffolds with epidermal growth factor for neural tissue engineering". Biomatter. 6 (1): e1231276. doi:10.1080/21592535.2016.1231276. PMC 5098722. PMID 27740881.
  23. ^ Tenchurin T, Lyundup A, Demchenko A, Krasheninnikov M, Balyasin M, Klabukov I, et al. (2017). "Modification of biodegradable fibrous scaffolds with Epidermal Growth Factor by emulsion electrospinning for promotion of epithelial cells proliferation". Гены и клетки (in Russian). 12 (4): 47–52. doi:10.23868/201707029. S2CID 90593089.
  24. ^ Del Angel-Mosqueda C, Gutiérrez-Puente Y, López-Lozano AP, Romero-Zavaleta RE, Mendiola-Jiménez A, Medina-De la Garza CE, et al. (September 2015). "Epidermal growth factor enhances osteogenic differentiation of dental pulp stem cells in vitro". Head & Face Medicine. 11: 29. doi:10.1186/s13005-015-0086-5. PMC 4558932. PMID 26334535.
  25. ^ Pache JC (2006-01-01). "Epidermal growth factors". In Laurent GJ, Shapiro SD (eds.). Encyclopedia of Respiratory Medicine. Oxford: Academic Press. pp. 129–133. doi:10.1016/b0-12-370879-6/00138-1. ISBN 978-0-12-370879-3. Retrieved 2020-11-30.

Further reading

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[edit]
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