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Epidermal growth factor
Epidermal growth factor
Epidermal growth factor or EGF is a growth factor that plays an important role in the regulation of cell growth, proliferation, and differentiation by binding to its receptor EGFR. Human EGF is a 6045-Da protein with 53 amino acid residuesand three intramolecular disulfide bonds.[2]
Epidermal growth factor (beta-urogastrone)
From Wikipedia, the free encyclopedia
History
History
The discovery of EGF won Stanley Cohen a Nobel Prize in Physiology and Medicine in 1986[3] and was patented for cosmetic use by Greg Brown in 1989.[4]
Function
Function
EGF results in cellular proliferation, differentiation, and survival.[5]
Source
Source
Platelets, Macrophages, Urine, Saliva, Milk, Plasma.[6]
Mechanism
Mechanism
EGF acts by binding with high affinity toepidermal 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, increasedglycolysis and protein synthesis, and increases in the expression of certain genesincluding the gene for EGFR - that ultimately lead to DNA synthesis and cell proliferation.[7]
EGF-family
EGF-family
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:[8]
- 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:
Where X represents any amino acid.[8]
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.[9]
EGF therapy
EGF therapy
Because of the increased risk of cancer by EGF, inhibiting it decreases cancer risk.[5] Such medications are so far mainly based on inhibiting the EGF receptor. Monoclonal antibodies are potential substances for this purpose.
Diagram showing key components of the MAPK/ERK pathway. In the diagram, "P" represents phosphate. Note EGF at the very top.
Rainbow colored NMR structure (N-terminus = blue, C-terminus = red) of the mouse epidermal growth factor.[1]
Available structures: 1ivo, 1jl9, 1nql, 1p9j
Identifiers
RNA expression pattern
Orthologs
[edit]
Interactions
Interactions
Epidermal growth factor has been shown to interact with Epidermal growth factor receptor[10][11] and PIK3R2.[12]
References
References
- ^ 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. PMID 10082370.
- ^ 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.
- ^ US patent 5618544, "Method of decreasing cutaneous senescence", granted , assigned to Bays Brown Dermatologics Inc
- ^ 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.
- ^ 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, Catelijne; Souriau Christelle, van Liempt Ellis, van de Poll Monique L M, van Zoelen Everardus J J (Jul. 2002). "Role of the N-terminus of epidermal growth factor in ErbB-2/ErbB-3 binding studied by phage display". Biochemistry (United States) 41 (27): 8732-41. ISSN 0006-2960. PMID 12093292.
- ^ Wong, L; Deb T B, Thompson S A, Wells A, Johnson G R (Mar. 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. (UNITED STATES) 274 (13): 8900-9. ISSN 0021-9258.PMID 10085134.
- ^ Gout, I; Dhand R, Panayotou G, Fry M J, Hiles I, Otsu M, Waterfield M D (Dec. 1992). "Expression and characterization of the p85 subunit of the phosphatidylinositol 3-kinase complex and a related p85 beta protein by using the baculovirus expression system". Biochem. J. (ENGLAND) 288 ( Pt 2): 395-405. ISSN 0264-6021. PMID 1334406.
External links
External links
Further reading
Further reading
- Boonstra J, Rijken P, Humbel B, et al. (1995). "The epidermal growth factor". Cell Biol. Int. 19 (5): 413–30. doi:10.1006/cbir.1995.1086.PMID 7640657.
- Dvorak B (2004). "Epidermal growth factor and necrotizing enterocolitis".Clinics in perinatology 31 (1): 183–92. doi:10.1016/j.clp.2004.03.015.PMID 15183666.
- Howell WM (2004). "Epidermal growth factor gene polymorphism and development of cutaneous melanoma". J. Invest. Dermatol. 123 (4): xx-xxi. doi:10.1111/j.0022-202X.2004.23308.x. PMID 15373802.
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