EGF Nob1986

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

Epidermal growth factor

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Epidermal growth factor (beta-urogastrone)
Rainbow colored NMR structure (N-terminus = blue, C-terminus = red) of the mouse epidermal growth factor.[1]
Available structures: 1ivo1jl91nql1p9j
Identifiers
SymbolsEGF; URG
External IDsOMIM131530 MGI95290HomoloGene1483
[show]Gene ontology
RNA expression pattern

More reference expression data

Orthologs
HumanMouse
Entrez195013645
EnsemblENSG00000138798ENSMUSG00000028017
UniprotP01133Q3UWD7
RefseqNM_001963(mRNA)
NP_001954(protein)
NM_010113(mRNA)
NP_034243(protein)
LocationChr 4: 111.05 - 111.15 MbChr 3: 129.67 - 129.75 Mb
Pubmedsearch[1][2]

Epidermal growth factor or EGF is a growth factor that plays an important role in the regulation of cell growthproliferation, 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]

Contents

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[edit]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]

[edit]Function

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

[edit]Source

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

[edit]Mechanism

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 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]

[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:[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]

[edit]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.

[edit]Interactions

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

[edit]References

  1. ^ PDB 1a3pBarnham 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.5560070808PMID 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.2003.11.041PMID 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.6144184PMID 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.2005.06.038PMID 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)00105-2PMID 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 0006-2960PMID 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 0264-6021PMID 1334406.

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