Epidermal growth factor
|, HOMG4, URG, epidermal growth factor, Epidermal growth factor|
|RNA expression pattern|
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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 with 53 amino acid residues and three intramolecular disulfide bonds.
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.
Epidermal growth factor can be found in urine, saliva, milk, and plasma. The production of epidermal growth factor has been found to be stimulated by testosterone.
EGF acts by binding with high affinity to epidermal growth factor receptor (EGFR) on the cell surface. This stimulates ligand-induced dimerization, 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.
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)
- Betacellulin (BTC)
- neuregulin-1 (NRG1)
- neuregulin-2 (NRG2)
- neuregulin-3 (NRG3)
- neuregulin-4 (NRG4).
All family members contain one or more repeats of the conserved amino acid sequence:
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.
Increased activity of the epidermal growth factor receptor (EGFR) 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. Thus EGF and EGFR have been exploited to develop imaging methods and targeted therapies against cancers overexpressing EGFR.
Pharmaceutical drugs developed for inhibiting the EGF receptor include gefitinib, erlotinib, afatinib and osimertinib for lung cancer, and Cetuximab for colon cancer. EGFR inhibitors are either tyrosine kinase inhibitors or monoclonal antibodies that slow down or halt cell growth. CimaVax-EGF, an active vaccine targeting EGF as the major ligand of EGFR, raises antibodies against EGF itself, thereby denying EGFR-dependent cancers of a proliferative stimulus; it is in use as a cancer therapy against non-small-cell lung carcinoma (the most common form of lung cancer) in Cuba, and is undergoing further trials for possible licensing in Japan, Europe, and the United States.
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|Wikimedia Commons has media related to Epidermal growth factor, EGF.|
- 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 (MeSH)
- EGF model in BioModels database