Epidermal growth factor

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Not to be confused with EF-G.
1a3p egf.png
Available structures
PDB Ortholog search: PDBe RCSB
Aliases EGF, HOMG4, URG, epidermal growth factor, Epidermal growth factor
External IDs OMIM: 131530 MGI: 95290 HomoloGene: 1483 GeneCards: 1950
RNA expression pattern
PBB GE EGF 206254 at tn.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 4: 109.91 – 110.01 Mb Chr 3: 129.68 – 129.76 Mb
PubMed search [1] [2]
View/Edit Human View/Edit Mouse

Epidermal growth factor (EGF) is a growth factor that stimulates cell growth, proliferation, and differentiation by binding to its receptor EGFR. Human EGF is a 6045-Da protein[3] with 53 amino acid residues and three intramolecular disulfide bonds.[4]

EGF was originally described independently as a secreted peptide found in the submaxillary glands of mice and in human urine. Initially, human EGF was known as urogastrone.[5]


EGF results in cellular proliferation, differentiation, and survival.[6] EGF is a low-molecular-weight polypeptide first purified from the mouse submandibular gland, but since then found in many human tissues including submandibular gland, parotid gland. Salivary EGF, which seems also regulated by dietary inorganic iodine, also plays an important physiological role in the maintenance of oro-esophageal and gastric tissue integrity. The biological effects of salivary EGF include healing of oral and gastroesophageal ulcers, inhibition of gastric acid secretion, stimulation of DNA synthesis as well as mucosal protection from intraluminal injurious factors such as gastric acid, bile acids, pepsin, and trypsin and to physical, chemical and bacterial agents.[7]

Biological sources[edit]

Epidermal growth factor can be found in urine, saliva, milk, and plasma.[8] The production of epidermal growth factor has been found to be stimulated by testosterone.


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 to epidermal growth factor receptor (EGFR) on the cell surface. This stimulates ligand-induced dimerization,[9] activating 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.[10]


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:[11]

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


Where X represents any amino acid.[11]

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.[12]


Epidermal growth factor has been shown to interact with epidermal growth factor receptor.[13][14]

Medical uses[edit]

Recombinant human epidermal growth factor, sold under the brand name Heberprot-P, is used to treat diabetic foot ulcers. It can be given by injection into the wound site,[15] or may be used topically.[16] Tentative evidence shows improved wound healing.[17] Safety has been poorly studied.[17]


  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Harris RC, Chung E, Coffey RJ (March 2003). "EGF receptor ligands". Experimental Cell Research. 284 (1): 2–13. doi:10.1016/S0014-4827(02)00105-2. PMID 12648462. 
  4. ^ Carpenter G, Cohen S (May 1990). "Epidermal growth factor". The Journal of Biological Chemistry. 265 (14): 7709–12. PMID 2186024. 
  5. ^ Hollenberg, MD; Gregory, H (May 1980). "Epidermal growth factor-urogastrone: biological activity and receptor binding of derivatives.". Molecular Pharmacology. 17 (3): 314–20. PMID 6248761. 
  6. ^ 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. 
  7. ^ Venturi S, Venturi M (2009). "Iodine in evolution of salivary glands and in oral health". Nutrition and Health. 20 (2): 119–134. doi:10.1177/026010600902000204. PMID 19835108. 
  8. ^ 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. 
  9. ^ Dawson JP, Berger MB, Lin CC, Schlessinger J, Lemmon MA, Ferguson KM (2005). "Epidermal growth factor receptor dimerization and activation require ligand-induced conformational changes in the dimer interface". Mol. Cell. Biol. 25 (17): 7734–42. doi:10.1128/MCB.25.17.7734-7742.2005. PMC 1190273free to read. PMID 16107719. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ Harris RC, Chung E, Coffey RJ (2003). "EGF receptor ligands". Exp. Cell. Res. 284 (1): 2–13. doi:10.1016/S0014-4827(02)00105-2. PMID 12648462. 
  13. ^ Stortelers C, Souriau C, van Liempt E, van de Poll ML, van Zoelen EJ (July 2002). "Role of the N-terminus of epidermal growth factor in ErbB-2/ErbB-3 binding studied by phage display". Biochemistry. 41 (27): 8732–41. doi:10.1021/bi025878c. PMID 12093292. 
  14. ^ Wong L, Deb TB, Thompson SA, Wells A, Johnson GR (March 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. 274 (13): 8900–9. doi:10.1074/jbc.274.13.8900. PMID 10085134. 
  15. ^ Berlanga, J.; Fernández, J. I.; López, E.; López, P. A.; del Río, A.; Valenzuela, C.; Baldomero, J.; Muzio, V.; Raíces, M.; Silva, R.; Acevedo, B. E.; Herrera, L. (2013). "Heberprot-P: a novel product for treating advanced diabetic foot ulcer". MEDICC Review. 15 (1): 11–15. PMID 23396236. 
  16. ^ Yang, S; Geng, Z; Ma, K; Sun, X; Fu, X (June 2016). "Efficacy of Topical Recombinant Human Epidermal Growth Factor for Treatment of Diabetic Foot Ulcer: A Systematic Review and Meta-Analysis.". The international journal of lower extremity wounds. 15 (2): 120–5. PMID 27151755. 
  17. ^ a b Martí-Carvajal, AJ; Gluud, C; Nicola, S; Simancas-Racines, D; Reveiz, L; Oliva, P; Cedeño-Taborda, J (28 October 2015). "Growth factors for treating diabetic foot ulcers.". The Cochrane database of systematic reviews (10): CD008548. PMID 26509249. 

Further reading[edit]

External links[edit]