Epidermal growth factor

Epidermal growth factor (beta-urogastrone)

Rainbow colored NMR structure (N-terminus = blue, C-terminus = red) of the mouse epidermal growth factor.[1]
Identifiers
Symbols EGF; URG
External IDs OMIM: 131530 MGI: 95290 HomoloGene: 1483 GeneCards: EGF Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 1950 13645
Ensembl ENSG00000138798 ENSMUSG00000028017
UniProt P01133 Q3UWD7
RefSeq (mRNA) NM_001963 NM_010113
RefSeq (protein) NP_001954 NP_034243
Location (UCSC) Chr 4:
111.05 – 111.15 Mb		 Chr 3:
129.67 – 129.75 Mb
PubMed search [1] [2]

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.[2]

Contents

History

The discovery of EGF won Stanley Cohen of Vanderbilt University a Nobel Prize in Physiology and Medicine in 1986[3] and was patented for cosmetic use by Greg Brown in 1989.[4]

Function

EGF results in cellular proliferation, differentiation, and survival.[5] 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.[6]

Biological Sources

Epidermal growth factor can be found in human platelets, macrophages, urine, saliva, milk, and plasma.[7]

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.[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

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.

Interactions

Epidermal growth factor has been shown to interact with Epidermal growth factor receptor[11][12] and PIK3R2.[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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2144085. 
  2. ^ Carpenter G, Cohen S (May 1990). "Epidermal growth factor". The Journal of Biological Chemistry 265 (14): 7709–12. PMID 2186024. http://www.jbc.org/cgi/reprint/265/14/7709. 
  3. ^ Hall K (1986). "The Nobel Prize in Physiology or Medicine 1986 - Presentation Speech". The Nobel Foundation. http://nobelprize.org/nobel_prizes/medicine/laureates/1986/presentation-speech.html. Retrieved 2009-04-24. 
  4. ^ US patent 5618544, Brown Gregory, "Method of decreasing cutaneous senescence", published 1997-04-08, 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.2003.11.041. PMID 15142631. 
  6. ^ Venturi S.; Venturi M. (2009). "Iodine in evolution of salivary glands and in oral health". Nutrition and Health 20 (2): 119–134. PMID 19835108. 
  7. ^ 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. 
  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. ^ 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. 
  10. ^ Harris RC, Chung E, and Coffey RJ. (2003). "EGF receptor ligands". Exp. Cell. Res. 284 (1): 2–13. doi:10.1016/S0014-4827(02)00105-2. PMID 12648462. 
  11. ^ 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. doi:10.1021/bi025878c. ISSN 0006-2960. PMID 12093292. 
  12. ^ 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. doi:10.1074/jbc.274.13.8900. ISSN 0021-9258. PMID 10085134. 
  13. ^ 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) (Pt 2): 395–405. ISSN 0264-6021. PMC 1132024. PMID 1334406. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1132024. 

External links

Further reading

Fibroblast

FGF receptor ligands: FGF1/FGF2/FGF5 · FGF3/FGF4/FGF6 · KGF (FGF7/FGF10/FGF22) · FGF8/FGF17/FGF18 · FGF9/FGF16/FGF20

FGF homologous factors: FGF11 · FGF12 · FGF13 · FGF14

hormone-like: FGF19 · FGF21 · FGF23
EGF-like domain
TGF-α · EGF  · HB-EGF
TGFβ pathway
Insulin-like
Platelet-derived
PDGFA · PDGFB · PDGFC · PDGFD
Vascular endothelial
VEGF-A · VEGF-B · VEGF-C · VEGF-D · PGF
Other
B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)