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. Human EGF is a 6045-Da protein with 53 amino acid residues and three intramolecular disulfide bonds.

Function
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.

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:


 * 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:

CX7CX4-5CX10-13CXCX8GXRC

Where X represents any amino acid.

This sequence contains 6 cysteine residues that form three intramolecular disulphide bonds. Disulphide bond formation generates three structural loops that are essential for high-affinity binding between members of the EGF-family and their cell-surface receptors.

EGF as Therapeutic Protein
EGF is currently being marketed as a therapeutic protein for the treatment of diabetic foot ulcers by at least three companies. Bharat Biotech International, a company based in India, is marketing EGF as REGEN-D, Daewoong Pharmaceutical, based in South Korea, is marketing EGF as Easyef, and the Center for Genetic Engineering and Biotechnology, in Cuba, is marketing EGF as CITOPROT-P. EGF is also used in a burn treatment cream product, Hebermin, manufactured by Heber Biotec S. A. in Cuba.