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 residues and three intramolecular disulfide bonds. [cite journal | author =Carpenter G, and Cohen S. | title =Epidermal growth factor | journal =J. Biol. Chem. | year=1990 | volume=265 | issue=14 | pages=7709–7712 | pmid = 2186024]

History

The discovery of EGF won Dr. Stanly Cohen a Nobel Prize in Physiology and Medicine in 1986 [ [http://nobelprize.org/nobel_prizes/medicine/laureates/1986/presentation-speech.html The Nobel Prize in Physiology or Medicine 1986 - Presentation Speech ] ] and was patented for cosmetic use by Dr. Greg Brown in 1989 [ [http://www.freepatentsonline.com/5618544.html Method of decreasing cutaneous senescence - Patent 5618544 ] ] .

Function

EGF results in cellular proliferation, differentiation, and survival. cite journal |author=Herbst RS |title=Review of epidermal growth factor receptor biology |journal=Int. J. Radiat. Oncol. Biol. Phys. |volume=59 |issue=2 Suppl |pages=21–6 |year=2004 |pmid=15142631 |doi=10.1016/j.ijrobp.2003.11.041]

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. [cite journal | author =Fallon JH, Seroogy KB."et al" | title=Epidermal growth factor immunoreactive material in the central nervous system: location and development | journal =Science | year=1984 | volume=224 | issue=4653 | pages=1107–1109 | pmid = 6144184 | doi=10.1126/science.6144184]

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:cite journal | author =Dreux AC, Lamb DJ. "et al." | title =The epidermal growth factor receptors and their family of ligands: their putative role in atherogenesis | journal =Atherosclerosis | year=2006 | volume=186 | issue=1 | pages=38–53 | pmid = 16076471 | doi =10.1016/j.atherosclerosis.2005.06.038]

*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:

CX₇CX_4-5CX_10-13CXCX₈GXRC

Where X represents any amino acid.

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.cite journal | author =Harris RC, Chung E, and Coffey RJ. | title =EGF receptor ligands | journal =Exp. Cell. Res. | year=2003 | volume=284 | issue=1 | pages=2–13 | pmid = 12648462 | doi =10.1016/S0014-4827(02)00105-2]

EGF therapy

Because of the increased risk of cancer by EGF, inhibiting it decreases cancer risk. Such medications are so far mainly based on inhibiting the EGF receptor. Monoclonal antibodies and small-molecule inhibitors are potential substances for this purpose.

References

External links

*EGF at the [http://www.hprd.org/protein/00578 Human Protein Reference Database] .
*

Further reading

PBB_Further_reading
citations =
*cite journal | author=Boonstra J, Rijken P, Humbel B, "et al." |title=The epidermal growth factor |journal=Cell Biol. Int. |volume=19 |issue= 5 |pages= 413–30 |year= 1995 |pmid= 7640657 |doi=10.1006/cbir.1995.1086
*cite journal | author=Dvorak B |title=Epidermal growth factor and necrotizing enterocolitis |journal=Clinics in perinatology |volume=31 |issue= 1 |pages= 183–92 |year= 2004 |pmid= 15183666 |doi= 10.1016/j.clp.2004.03.015
*cite journal | author=Howell WM |title=Epidermal growth factor gene polymorphism and development of cutaneous melanoma |journal=J. Invest. Dermatol. |volume=123 |issue= 4 |pages= xx-xxi |year= 2004 |pmid= 15373802 |doi= 10.1111/j.0022-202X.2004.23308.x

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