EGF Nob1986

http://en.wikipedia.org/wiki/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

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

EGF results in cellular proliferation, differentiation, and survival.[5]

Source

Platelets, Macrophages, Urine, Saliva, Milk, Plasma.[6]

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 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]

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

CX7CX4-5CX10-13CXCX8GXRC

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

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

External IDs

Location

Pubmedsearch

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Interactions

Epidermal growth factor has been shown to interact with Epidermal growth factor receptor[10][11] and PIK3R2.[12]

References

    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. PMID 10082370.
    2. ^ Carpenter G, Cohen S (May 1990). "Epidermal growth factor". The Journal of Biological Chemistry 265 (14): 7709–12. PMID 2186024.
    3. ^ Hall K (1986). "The Nobel Prize in Physiology or Medicine 1986 - Presentation Speech". The Nobel Foundation. Retrieved 2009-04-24.
    4. ^ US patent 5618544, "Method of decreasing cutaneous senescence", granted , assigned to Bays Brown Dermatologics Inc
    5. ^ 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.
    6. ^ 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.
    7. ^ 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.
    8. ^ 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.
    9. ^ 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.
    10. ^ 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.
    11. ^ 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.
    12. ^ 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

Further reading

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