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 with 53 amino acid residues and three intramolecular disulfide
bonds.
History The discovery of EGF won Stanley Cohen and
Rita Levi-Montalcini the Nobel Prize in Physiology or Medicine in 1986.
Function EGF results in cellular proliferation, differentiation,
and survival.
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.
Biological sources Epidermal growth factor can be found in human
platelets, macrophages, urine, saliva, milk, and plasma.
Mechanism
EGF acts by binding with high affinity to epidermal growth factor receptor on the cell
surface and stimulating the intrinsic protein-tyrosine kinase activity of the receptor.
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
transforming growth factor-α Amphiregulin
Epiregulin Epigen
Betacellulin neuregulin-1
neuregulin-2 neuregulin-3
neuregulin-4.
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 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.
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.
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.
References
Further reading
External links Shaanxi Zhongbang Pharma-Tech Co., Ltd.-Supply
of Epidermal Growth Factor EGF at the Human Protein Reference Database.
Epidermal growth factor at the US National Library of Medicine Medical Subject Headings
EGF model in BioModels database