Epidermal growth factor

Epidermal growth factor (beta-urogastrone)
Rainbow colored NMR structure (N-terminus = blue, C-terminus = red) of the mouse epidermal growth factor.[1]
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	1950	13645
Ensembl	ENSG00000138798	ENSMUSG00000028017
Uniprot	P01133	Q3UWD7
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]

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.^[2]

History

The discovery of EGF won Stanely Cohen a Nobel Prize in Physiology and Medicine in 1986^[3] and was patented for cosmetic use by Greg Brown in 1989.^[4]

Function

EGF results in cellular proliferation, differentiation, and survival.^[5]

Source

Platelets, Macrophages, Urine, Saliva, Milk, Plasma.^[6]

Mechanism

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 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.^[7]

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:^[8]

• 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.^[8]

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.^[9]

EGF therapy

Because of the increased risk of cancer by EGF, inhibiting it decreases cancer risk.^[5] Such medications are so far mainly based on inhibiting the EGF receptor. Monoclonal antibodies are potential substances for this purpose.

References

External links

• EGF at the Human Protein Reference Database.
• MeSH Epidermal+growth+factor
• EGF model in BioModels database

Further reading