Dictionary - Definition of EPIDERMAL GROWTH FACTOR

Epidermal growth factor

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Epidermal growth factor (beta-urogastrone)

PDB rendering based on 1ivo.

Available structures: 1ivo, 1jl9, 1nql, 1p9j

Identifiers

Symbols

EGF; URG

External IDs

OMIM: 131530 MGI: 95290 HomoloGene: 1483

Gene ontology
Molecular function:	• epidermal growth factor receptor-activating ligand activity • calcium ion binding • protein binding • growth factor activity
Cellular component:	• extracellular region • extracellular space • nucleus • plasma membrane • integral to membrane
Biological process:	• activation of MAPKK activity • activation of MAPK activity • DNA replication • chromosome organization and biogenesis (sensu Eukaryota) • epidermal growth factor receptor signaling pathway • positive regulation of cell proliferation • branching morphogenesis of a tube • regulation of peptidyl-tyrosine phosphorylation

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

Entrez

Ensembl

Uniprot

Refseq

NM_001963 (mRNA)
NP_001954 (protein)

NM_010113 (mRNA)
NP_034243 (protein)

Location

Chr 4: 111.05 - 111.15 Mb

Chr 3: 129.67 - 129.75 Mb

Pubmed search

[1]

[2]

Diagram showing key components of the MAPK/ERK pathway. In the diagram, "P" represents phosphate. Note EGF at the very top.

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.^[1]

History

The discovery of EGF won Dr. Stanley Cohen a Nobel Prize in Physiology and Medicine in 1986^[2] and was patented for cosmetic use by Dr. Greg Brown in 1989^[3].

Function

EGF results in cellular proliferation, differentiation, and survival. ^[4]

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.^[5]

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:^[6]

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 X represents any amino acid.^[6]

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.^[7]

EGF therapy

Because of the increased risk of cancer by EGF, inhibiting it decreases cancer risk.^[4] Such medications are so far mainly based on inhibiting the EGF receptor. Monoclonal antibodies and small-molecule inhibitors are potential substances for this purpose.

References

Carpenter G, and Cohen S. (1990). "Epidermal growth factor". J. Biol. Chem. 265 (14): 7709–7712. PMID 2186024.
The Nobel Prize in Physiology or Medicine 1986 - Presentation Speech
Method of decreasing cutaneous senescence - Patent 5618544
^a ^b Herbst RS (2004). "Review of epidermal growth factor receptor biology". Int. J. Radiat. Oncol. Biol. Phys. 59 (2 Suppl): 21–6. doi:10.1016/j.ijrobp.2003.11.041. PMID 15142631.
Fallon JH, Seroogy KB.et al (1984). "Epidermal growth factor immunoreactive material in the central nervous system: location and development". Science 224 (4653): 1107–1109. doi:10.1126/science.6144184. PMID 6144184.
^a ^b Dreux AC, Lamb DJ. et al. (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.
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.

External links

EGF at the Human Protein Reference Database.
MeSH Epidermal+growth+factor

Boonstra J, Rijken P, Humbel B, et al. (1995). "The epidermal growth factor". Cell Biol. Int. 19 (5): 413–30. doi:10.1006/cbir.1995.1086. PMID 7640657.
Dvorak B (2004). "Epidermal growth factor and necrotizing enterocolitis". Clinics in perinatology 31 (1): 183–92. doi:10.1016/j.clp.2004.03.015. PMID 15183666.
Howell WM (2004). "Epidermal growth factor gene polymorphism and development of cutaneous melanoma". J. Invest. Dermatol. 123 (4): xx-xxi. doi:10.1111/j.0022-202X.2004.23308.x. PMID 15373802.

Growth factors

Fibroblast	FGF receptor ligands: 1 (acidic)/2 (basic)/5 · 3/4/6 · KGF (7/10/22) · 8/17/18 · 9/16/20 FGF homologous factors: 11 · 12 · 13 · 14 hormone-like: 19 · 21 · 23

EGF-like domain	TGFα · Epidermal · Heparin-binding EGF-like

TGFβ pathway	TGFβ (1, 2, 3)

Insulin-like	1 · 2

Platelet-derived	A · B · C · D

Vascular endothelial	A · B · C · D · PGF

Other	Nerve · Hepatocyte

see also growth factor receptors

Hormones: gastrointestinal hormones

CCK - EGF - GIP - Gastrin releasing peptide - Gastrins - Proglucagon - Motilin - Peptide YY -Prokineticin - Secretin - VIP

Source: adapted by the editor from Wikipedia, the free encyclopedia; from the article "Epidermal growth factor". Image Credit.

Expressions	Domain	Definition
Epidermal Growth Factor	Health	A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone.epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. (references)
Epidermal growth factor (EGF)	Geology	A polypeptide growth factor that stimulates the growth of epithelial cells. It was discovered by Stanley Cohen, and a part of the gene which codes for the receptor on the cells that heed its signals is extremely similar to the erb-b oncogene (proto-cancer gene). (references)
Epidermal growth factor receptor	Health	EGFR. The protein found on the surface of some cells and to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of cancer cells, so these cells may divide excessively in the presence of epidermal growth factor. Also known as ErbB1 or HER1. (references)
Receptor, Epidermal Growth Factor	Health	A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for epidermal growth factor and EGF related peptides including transforming growth factor alpha, amphiregulin, and heparin-binding EGF-like growth factor. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell. EC 2.7.11.-. (references)
Source: compiled by the editor from various references; see credits.			Top

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Specialty Expressions: EPIDERMAL GROWTH FACTOR

Extended Definition: Epidermal growth factor