Epidermal growth factor

Not to be confused with EF-G.
Epidermal growth factor

Rainbow colored NMR structure (N-terminus = blue, C-terminus = red) of the mouse epidermal growth factor.[1]
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsEGF ; HOMG4; URG
External IDsOMIM: 131530 MGI: 95290 HomoloGene: 1483 ChEMBL: 5734 GeneCards: EGF Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez195013645
EnsemblENSG00000138798ENSMUSG00000028017
UniProtP01133P01132
RefSeq (mRNA)NM_001178130NM_010113
RefSeq (protein)NP_001171601NP_034243
Location (UCSC)Chr 4:
110.83 – 110.93 Mb		Chr 3:
129.68 – 129.76 Mb
PubMed search

Epidermal growth factor or 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[2] with 53 amino acid residues and three intramolecular disulfide bonds.[3]

Function

EGF results in cellular proliferation, differentiation, and survival.[4] 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.[5]

Biological sources

Epidermal growth factor can be found in macrophages, urine, saliva, milk, and plasma.[6]

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 to epidermal growth factor receptor (EGFR) on the cell surface. This stimulates ligand-induced dimerization,[7] 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.[8]

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:[9]

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

CX7CX4-5CX10-13CXCX8GXRC

Where X represents any amino acid.[9]

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.[10]

EGF therapy

Increased activity of the receptor for EGF has been observed in certain types of cancer, often correlated with mutations in the receptor and abnormal function such as constitutive receptor signalling independent of the levels of EGF or of binding of EGF.[11]

Pharmaceutical drugs developed for inhibiting the EGF receptor include Gefitinib, Erlotinib, and Afatinib for lung cancer, and Cetuximab for colon cancer. Monoclonal antibodies are potential substances for this purpose.

Interactions

Epidermal growth factor has been shown to interact with epidermal growth factor receptor.[12][13]

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. PMC 2144085. PMID 10082370.
  2. ↑ 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.
  3. ↑ Carpenter G, Cohen S (May 1990). "Epidermal growth factor". The Journal of Biological Chemistry 265 (14): 7709–12. PMID 2186024.
  4. ↑ 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.
  5. ↑ 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.
  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. ↑ 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 1190273. PMID 16107719.
  8. ↑ 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.
  9. ↑ 9.0 9.1 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.
  10. ↑ 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.
  11. ↑ Lurje G., et al., "EGFR Signalling and Drug Discovery", Oncology 77: 400-410 (2009)
  12. ↑ 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.
  13. ↑ 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.

Further reading

  • Boonstra J, Rijken P, Humbel B, Cremers F, Verkleij A, van Bergen en Henegouwen P (1995). "The epidermal growth factor". Cell Biol. Int. 19 (5): 413–30. doi:10.1006/cbir.1995.1086. PMID 7640657.
  • Dvorak B (2004). "Epidermal growth factor and necrotizing enterocolitis". Clinics in perinatology 31 (1): 183–92. doi:10.1016/j.clp.2004.03.015. PMID 15183666.
  • Howell WM (2004). "Epidermal growth factor gene polymorphism and development of cutaneous melanoma". J. Invest. Dermatol. 123 (4): xx–xxi. doi:10.1111/j.0022-202X.2004.23308.x. PMID 15373802.

External links

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