Epidermal growth factor
From Wikipedia, the free encyclopedia
Epidermal growth factor or EGF is a growth factor that plays an important role in the regulation of cell growth, proliferation, and differentiation. It also increases cancer risk.[1] Human EGF is a 6045-Da protein with 53 amino acid residues and three intramolecular disulfide bonds.[2]
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[edit] History
The discovery of EGF won Dr. Stanly Cohen a Nobel Prize in Physiology and Medicine in 1986[3] and was patented for cosmetic use by Dr. Greg Brown in 1989[4].
[edit] Function
EGF results in cellular proliferation, differentiation, and survival. [1] This, in turn, results in an increased risk of cancer. [1]
[edit] Mechanism
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.[5]
[edit] 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:[6]
- 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)
- neureguline-4 (NRG4).
All family members contain one or more repeats of the conserved amino acid sequence:
Where X represents any amino acid.[6]
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.[7]
[edit] EGF therapy
Because of the increased risk of cancer by EGF, inhibiting it decreases cancer risk.[1] Such medications are so far mainly based on inhibiting the EGF receptor. Monoclonal antibodies and small-molecule inhibitors are potential substances for this purpose.
[edit] References
- ^ a b c d Herbst RS (2004). "Review of epidermal growth factor receptor biology". Int. J. Radiat. Oncol. Biol. Phys. 59 (2 Suppl): 21-6. doi:. PMID 15142631.
- ^ Carpenter G, and Cohen S. (1990). "Epidermal growth factor". J. Biol. Chem. 265 (14): 7709-7712. PMID 2186024.
- ^ The Nobel Prize in Physiology or Medicine 1986 - Presentation Speech
- ^ Method of decreasing cutaneous senescence - Patent 5618544
- ^ Fallon JH, Seroogy KB.et al (1984). "Epidermal growth factor immunoreactive material in the central nervous system: location and development". Science 224 (4653): 1107-1109. doi:. PMID 6144184.
- ^ a b Dreux AC, Lamb DJ. et al. (2006). "The epidermal growth factor receptors and their family of ligands: their putative role in atherogenesis". Atherosclerosis 186 (1): 38-53. doi:. PMID 16076471.
- ^ Harris RC, Chung E, and Coffey RJ. (2003). "EGF receptor ligands". Exp. Cell. Res. 284 (1): 2-13. doi:. PMID 12648462.
[edit] External links
[edit] Further reading
- Boonstra J, Rijken P, Humbel B, et al. (1995). "The epidermal growth factor.". Cell Biol. Int. 19 (5): 413-30. doi:. PMID 7640657.
- Dvorak B (2004). "Epidermal growth factor and necrotizing enterocolitis.". Clinics in perinatology 31 (1): 183-92. doi:. PMID 15183666.
- Howell WM (2004). "Epidermal growth factor gene polymorphism and development of cutaneous melanoma.". J. Invest. Dermatol. 123 (4): xx-xxi. doi:. PMID 15373802.
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