Epidermal growth factor

Epidermal growth factor or EGF is a is_associated_with::growth factor that stimulates is_associated_with::cell growth, proliferation, and differentiation by binding to its receptor EGFR. Human EGF is a 6045-Da is_associated_with::protein with 53 amino acid residues and three intramolecular is_associated_with::disulfide bonds.

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 is_associated_with::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 macrophages, urine, saliva, milk, and plasma.

Mechanism
EGF acts by binding with high affinity to is_associated_with::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 is_associated_with::tyrosine kinase activity, in turn, initiates a is_associated_with::signal transduction cascade that results in a variety of biochemical changes within the cell - a rise in intracellular is_associated_with::calcium levels, increased is_associated_with::glycolysis and is_associated_with::protein synthesis, and increases in the expression of certain is_associated_with::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:


 * is_associated_with::Heparin-binding EGF-like growth factor (HB-EGF)
 * transforming growth factor-α (TGF-α)
 * is_associated_with::Amphiregulin (AR)
 * is_associated_with::Epiregulin (EPR)
 * is_associated_with::Epigen
 * is_associated_with::Betacellulin (BTC)
 * is_associated_with::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:

CX7CX4-5CX10-13CXCX8GXRC

Where X represents any is_associated_with::amino acid.

This sequence contains 6 is_associated_with::cysteine residues that form three intramolecular is_associated_with::disulfide bonds. Disulfide bond formation generates three structural loops that are essential for high-affinity binding between members of the EGF-family and their is_associated_with::cell-surface receptors.

EGF therapy
Increased activity of the is_associated_with::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/or EGFR have been exploited to develop imaging methods and targeted therapies against cancers overexpressing EGFR.

Pharmaceutical drugs developed for inhibiting the EGF receptor include is_associated_with::Gefitinib, is_associated_with::Erlotinib, and is_associated_with::Afatinib for is_associated_with::lung cancer, and is_associated_with::Cetuximab for is_associated_with::colon cancer. is_associated_with::Monoclonal antibodies are potential substances for this purpose. is_associated_with::CimaVax-EGF, an active is_associated_with::vaccine targeting EGF as the major is_associated_with::ligand of EGF, raises antibodies against EGF itself, thereby denying EGFR-dependent cancers of a proliferative stimulus; it is in use as a cancer therapy against is_associated_with::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.

Imaging agents have been developed which identify EGFR-dependent cancers using labeled EGF. or anti-EGFR

Interactions
Epidermal growth factor has been shown to interact with is_associated_with::epidermal growth factor receptor.