Epidermal growth factor

Epidermal growth factor
	; Rainbow colored NMR structure (N-terminus = blue, C-terminus = red) of the mouse epidermal growth factor.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1IVO, 1JL9, 1NQL, 1P9J, 2KV4, 3NJP
Identifiers
Symbols	EGF; HOMG4; URG
External IDs	OMIM: 131530 MGI: 95290 HomoloGene: 1483 ChEMBL: 5734 GeneCards: EGF Gene
Gene Ontology
Molecular function	• epidermal growth factor receptor binding; • calcium ion binding; • protein binding; • growth factor activity; • transmembrane receptor protein tyrosine kinase activator activity;
Cellular component	• extracellular region; • extracellular space; • plasma membrane; • integral to membrane; • platelet alpha granule lumen;
Biological process	• activation of MAPKK activity; • angiogenesis; • platelet degranulation; • DNA replication; • signal transduction; • activation of transmembrane receptor protein tyrosine kinase activity; • epidermal growth factor receptor signaling pathway; • STAT protein import into nucleus; • blood coagulation; • positive regulation of cell proliferation; • fibroblast growth factor receptor signaling pathway; • positive regulation of peptidyl-threonine phosphorylation; • peptidyl-tyrosine phosphorylation; • positive regulation of cerebellar granule cell precursor proliferation; • platelet activation; • positive regulation of catenin import into nucleus; • negative regulation of epidermal growth factor receptor signaling pathway; • positive regulation of phosphorylation; • positive regulation of DNA binding; • positive regulation of MAP kinase activity; • innate immune response; • positive regulation of epidermal growth factor-activated receptor activity; • positive regulation of mitosis; • positive regulation of transcription, DNA-dependent; • neurotrophin TRK receptor signaling pathway; • phosphatidylinositol-mediated signaling; • branching morphogenesis of an epithelial tube; • negative regulation of secretion; • mammary gland alveolus development; • ERK1 and ERK2 cascade; • regulation of calcium ion import; • negative regulation of cholesterol efflux; • positive regulation of hyaluronan biosynthetic process; • regulation of protein localization to cell surface; • positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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Epidermal growth factor or EGF is a growth factor that stimulates cell growth, proliferation, and differentiation by binding to its receptor EGFR. Human EGF is a 6045-Da protein^[2] with 53 amino acid residues and three intramolecular disulfide bonds.^[3]

History [edit]

The discovery of EGF won Stanley Cohen and Rita Levi-Montalcini a Nobel Prize in Physiology and Medicine in 1986.^[4]

Function [edit]

EGF results in cellular proliferation, differentiation, and survival.^[5] EGF is a low-molecular-weight polypeptide first purified from the mouse submandibular gland, but since then found in many human tissues including submandibular gland, parotid gland. Salivary EGF, which seems also 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.^[6]

Biological sources [edit]

Epidermal growth factor can be found in human platelets, macrophages, urine, saliva, milk, and plasma.^[7]

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 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 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.^[8]

EGF-family [edit]

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:^[9]

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_10-13CXCX₈GXR C

Where X represents any amino acid.^[9]

This sequence contains 6 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.^[10]

EGF therapy [edit]

Because of the increased risk of cancer by EGF, epidermal growth factor receptor inhibition decreases cancer risk.^[5] Pharmaceutical drugs developed for this purpose include gefitinib and erlotinib for lung cancer, and cetuximab for colon cancer. Monoclonal antibodies are potential substances for this purpose.

Interactions [edit]

Epidermal growth factor has been shown to interact with epidermal growth factor receptor.^[11]^[12]

References [edit]

^ PDB 1a3p; Barnham KJ, Torres AM, Alewood D, Alewood PF, Domagala T, Nice EC, Norton RS (August 1998). "Role of the 6-20 disulfide bridge in the structure and activity of epidermal growth factor". Protein Science 7 (8): 1738–49. doi:10.1002/pro.5560070808. PMC 2144085. PMID 10082370.
^ Harris RC, Chung E, Coffey RJ (March 2003). "EGF receptor ligands". Experimental Cell Research 284 (1): 2–13. PMID 12648462.
^ Carpenter G, Cohen S (May 1990). "Epidermal growth factor". The Journal of Biological Chemistry 265 (14): 7709–12. PMID 2186024.
^ Hall K (1986). "The Nobel Prize in Physiology or Medicine 1986 - Presentation Speech". The Nobel Foundation. Retrieved 2009-04-24.
^ ^a ^b 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.
^ Venturi S.; Venturi M. (2009). "Iodine in evolution of salivary glands and in oral health". Nutrition and Health 20 (2): 119–134. doi:10.1177/026010600902000204. PMID 19835108.
^ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease. St. Louis, Mo: Elsevier Saunders. ISBN 0-7216-0187-1.
^ Fallon JH, Seroogy KB, Loughlin SE, Morrison RS, Bradshaw RA, Knaver DJ, Cunningham DD (June 1984). "Epidermal growth factor immunoreactive material in the central nervous system: location and development". Science 224 (4653): 1107–9. doi:10.1126/science.6144184. PMID 6144184.
^ ^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.
^ Harris RC, Chung E, and Coffey RJ. (2003). "EGF receptor ligands". Exp. Cell. Res. 284 (1): 2–13. doi:10.1016/S0014-4827(02)00105-2. PMID 12648462.
^ 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.
^ 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". J. Biol. Chem. 274 (13): 8900–9. doi:10.1074/jbc.274.13.8900. PMID 10085134.

External links [edit]

Wikimedia Commons has media related to: Epidermal growth factor, EGF

Shaanxi Zhongbang Pharma-Tech Co., Ltd.-Supply of Epidermal Growth Factor
EGF at the Human Protein Reference Database.
Epidermal growth factor at the US National Library of Medicine Medical Subject Headings (MeSH)
EGF model in BioModels database

[pmid10082370-1] PDB 1a3p; Barnham KJ, Torres AM, Alewood D, Alewood PF, Domagala T, Nice EC, Norton RS (August 1998). "Role of the 6-20 disulfide bridge in the structure and activity of epidermal growth factor". Protein Science 7 (8): 1738–49. doi:10.1002/pro.5560070808. PMC 2144085. PMID 10082370.

[pmid12648462-2] Harris RC, Chung E, Coffey RJ (March 2003). "EGF receptor ligands". Experimental Cell Research 284 (1): 2–13. PMID 12648462.

[pmid2186024-3] Carpenter G, Cohen S (May 1990). "Epidermal growth factor". The Journal of Biological Chemistry 265 (14): 7709–12. PMID 2186024.

[urlThe_Nobel_Prize_in_Physiology_or_Medicine_1986_-_Presentation_Speech-4] Hall K (1986). "The Nobel Prize in Physiology or Medicine 1986 - Presentation Speech". The Nobel Foundation. Retrieved 2009-04-24.

[Herbst-5] 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.

[6] Venturi S.; Venturi M. (2009). "Iodine in evolution of salivary glands and in oral health". Nutrition and Health 20 (2): 119–134. doi:10.1177/026010600902000204. PMID 19835108.

[isbn0-7216-0187-1-7] Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease. St. Louis, Mo: Elsevier Saunders. ISBN 0-7216-0187-1.

[pmid6144184-8] Fallon JH, Seroogy KB, Loughlin SE, Morrison RS, Bradshaw RA, Knaver DJ, Cunningham DD (June 1984). "Epidermal growth factor immunoreactive material in the central nervous system: location and development". Science 224 (4653): 1107–9. doi:10.1126/science.6144184. PMID 6144184.

[dreux-9] 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.

[harris-10] Harris RC, Chung E, and Coffey RJ. (2003). "EGF receptor ligands". Exp. Cell. Res. 284 (1): 2–13. doi:10.1016/S0014-4827(02)00105-2. PMID 12648462.

[pmid12093292-11] 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.

[pmid10085134-12] 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". J. Biol. Chem. 274 (13): 8900–9. doi:10.1074/jbc.274.13.8900. PMID 10085134.

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Epidermal growth factor

Contents

History [edit]

Function [edit]

Biological sources [edit]

Mechanism [edit]

EGF-family [edit]

EGF therapy [edit]

Interactions [edit]

References [edit]

Further reading [edit]

External links [edit]

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