Epidermal growth factor

Epidermal growth factor (EGF) is a protein that stimulates cell growth and differentiation by binding to its receptor, EGFR. Human EGF is 6-kDa<ref name="pmid12648462">Template:Cite journal</ref> and has 53 amino acid residues and three intramolecular disulfide bonds.<ref name="pmid2186024">Template:Cite journal</ref>

EGF was originally described as a secreted peptide found in the submaxillary glands of mice and in human urine. EGF has since been found in many human tissues, including platelets,<ref name="Custo">Template:Cite journal</ref> submandibular gland (submaxillary gland),<ref name="Venturi2009" /> and parotid gland.<ref name=Venturi2009/> Initially, human EGF was known as urogastrone.<ref name=":0">Template:Cite journal</ref>

Structure

Template:Missing information In humans, EGF has 53 amino acids (sequence NSDSECPLSHDGYCLHDGVCMYIEALDKYACNCVVGYIGERCzYRDLKWWELR),<ref name="pmid2186024" /> with a molecular mass of around 6 kDa.<ref name="pmid12648462" /> It contains three disulfide bridges (Cys6-Cys20, Cys14-Cys31, Cys33-Cys42).<ref name="pmid2186024" />

Function

EGF, via binding to its cognate receptor, results in cellular proliferation, differentiation, and survival.<ref name="Herbst">Template:Cite journal</ref>

Salivary EGF, which seems to be 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.<ref name=Venturi2009>Template:Cite journal</ref>

Biological sources

The Epidermal growth factor can be found in platelets,<ref name="Custo" /> urine, saliva, milk, tears, and blood plasma.<ref name="isbn0-7216-0187-1">Template:Cite book</ref> It can also be found in the submandibular glands,<ref name="Venturi2009" /><ref name=":1">Template:Citation</ref> and the parotid gland.<ref name="Venturi2009" /><ref name=":1" /> The production of EGF has been found to be stimulated by testosterone.Template:Citation needed

Polypeptide growth factors

Template:Split section portions Polypeptide growth factors include:<ref>Template:Cite book</ref>

Sr.No	Growth factor	Source	Major function
1	Epidermal growth factor (EGF)	Salivary gland	Stimulates growth of epidermal and epithelial cells
2	Platelet derived growth factor	Platelets	Stimulates growth of mesenchymal cells, promotes wound healing
3	Transforming growth factor-alpha (TGF-α)	Epithelial cell	Similar to EGF
4	Transforming growth factor-beta (TGF-β)	Platelets, Kidney, Placenta	Inhibitory effect on cultures tumor cell
5	Erythropoietin	Kidney	Stimulates development of erythropoietic cells
6	Nerve growth factor (NGF)	Salivary gland	Stimulates the growth of sensory nerves
7	Insulin-like growth factor	Serum	Stimulates incorporation of sulfates into cartilage, exerts insulin-like action on certain cells
8	Tumor necrosis factor	Monocytes	Necrosis of tumor cells
9	Interleukin-1	Monocytes, Leukocytes	Stimulates synthesis of IL-2
10	Interleukin-2	Lymphocytes	Stimulates growth and maturation of T-cells

Mechanism

File:MAPKpathway diagram.svg

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,<ref name="pmid16107719">Template:Cite journal</ref> 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.<ref name="pmid6144184">Template:Cite journal</ref>

EGF-family / EGF-like domain

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} 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:<ref name="dreux">Template:Cite journal</ref>

• Heparin-binding EGF-like growth factor (HB-EGF)
• transforming growth factor-α (TGF-α)
• Amphiregulin (AR)
• Epiregulin (EPR)
• Epigen
• 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:

CX₇CX_4-5CX_10-13CXCX₈GXRC

Where C is cysteine, G is glycine, R is arginine, and X represents any amino acid.<ref name=dreux/>

This sequence contains six 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.<ref name="pmid12648462" />

Interactions

Epidermal growth factor has been shown to interact with epidermal growth factor receptors.<ref name="pmid12093292">Template:Cite journal</ref><ref name="pmid10085134">Template:Cite journal</ref>

Medical uses

Recombinant human epidermal growth factor, sold under the brand name Heberprot-P, is used to treat diabetic foot ulcers. It can be given by injection into the wound site,<ref name=Ber2013>Template:Cite journal</ref> or may be used topically.<ref>Template:Cite journal</ref> Tentative evidence shows improved wound healing.<ref name=Mar2015>Template:Cite journal</ref> Safety has been poorly studied.<ref name=Mar2015/>

EGF is used to modify synthetic scaffolds for manufacturing of bioengineered grafts by emulsion electrospinning or surface modification methods.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Bone regeneration

EGF plays an enhancer role on the osteogenic differentiation of dental pulp stem cells (DPSCs) because it is capable of increasing extracellular matrix mineralization. A low concentration of EGF (10 ng/ml) is sufficient to induce morphological and phenotypic changes. These data suggests that DPSCs in combination with EGF could be an effective stem cell-based therapy to bone tissue engineering applications in periodontics and oral implantology.<ref>Template:Cite journal</ref>

History

EGF was the second growth factor to be identified.<ref>Template:Cite book</ref> Initially, human EGF was known as urogastrone.<ref name=":0" /> Stanley Cohen discovered EGF while working with Rita Levi-Montalcini at the Washington University in St. Louis during experiments researching nerve growth factor. For these discoveries Levi-Montalcini and Cohen were awarded the 1986 Nobel Prize in Physiology or Medicine.

Further reading

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External links

• Shaanxi Zhongbang Pharma-Tech Co., Ltd.-Supply of Epidermal Growth Factor
• EGF at the Human Protein Reference Database Template:Webarchive.
• Template:MeshName
• EGF model in BioModels database