urogastrone

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/12/20 23:17:55」(JST)

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Epidermal growth factor
Rainbow colored NMR structure (N-terminus = blue, C-terminus = red) of the mouse epidermal growth factor.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1IVO, 1JL9, 1NQL, 1P9J, 2KV4, 3NJP
Identifiers
Symbols	EGF; HOMG4; URG
External IDs	OMIM: 131530 MGI: 95290 HomoloGene: 1483 ChEMBL: 5734 GeneCards: EGF Gene
Gene Ontology Molecular function • epidermal growth factor receptor binding • calcium ion binding • protein binding • growth factor activity • transmembrane receptor protein tyrosine kinase activator activity Cellular component • extracellular region • extracellular space • plasma membrane • integral to membrane • platelet alpha granule lumen Biological process • activation of MAPKK activity • angiogenesis • platelet degranulation • DNA replication • signal transduction • activation of transmembrane receptor protein tyrosine kinase activity • epidermal growth factor receptor signaling pathway • STAT protein import into nucleus • blood coagulation • positive regulation of cell proliferation • fibroblast growth factor receptor signaling pathway • positive regulation of peptidyl-threonine phosphorylation • peptidyl-tyrosine phosphorylation • positive regulation of cerebellar granule cell precursor proliferation • platelet activation • positive regulation of catenin import into nucleus • negative regulation of epidermal growth factor receptor signaling pathway • positive regulation of phosphorylation • positive regulation of DNA binding • positive regulation of MAP kinase activity • innate immune response • positive regulation of epidermal growth factor-activated receptor activity • positive regulation of mitosis • positive regulation of transcription, DNA-dependent • neurotrophin TRK receptor signaling pathway • phosphatidylinositol-mediated signaling • branching morphogenesis of an epithelial tube • negative regulation of secretion • mammary gland alveolus development • ERK1 and ERK2 cascade • regulation of calcium ion import • negative regulation of cholesterol efflux • positive regulation of hyaluronan biosynthetic process • regulation of protein localization to cell surface • positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1950	13645
Ensembl	ENSG00000138798	ENSMUSG00000028017
UniProt	P01133	P01132
RefSeq (mRNA)	NM_001178130	NM_010113
RefSeq (protein)	NP_001171601	NP_034243
Location (UCSC)	Chr 4: 110.83 – 110.93 Mb	Chr 3: 129.68 – 129.76 Mb
PubMed search	[1]	[2]

Epidermal growth factor or 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.

History

The discovery of EGF won Stanley Cohen and Rita Levi-Montalcini the Nobel Prize in Physiology or Medicine in 1986.

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 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 human platelets, macrophages, urine, saliva, milk, and plasma.

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.

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:

• 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.

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.

EGF therapy

Increased activity of the receptor for EGF 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.

Pharmaceutical drugs developed for inhibiting the EGF receptor include Gefitinib and Erlotinib for lung cancer, and Cetuximab for colon cancer. Monoclonal antibodies are potential substances for this purpose.

Interactions

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

References

Further reading

• 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. 

External links

• 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

English Journal

• Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer: A new era begins.

• Remon J, Morán T, Majem M, Reguart N, Dalmau E, Márquez-Medina D, Lianes P.SourceMedical Oncology Department, Hospital de Mataró, Carretera de la Cirera, s/n, 08304 Mataró, Barcelona, Spain. Electronic address: jremon@csdm.cat.
• Cancer treatment reviews.Cancer Treat Rev.2014 Feb;40(1):93-101. doi: 10.1016/j.ctrv.2013.06.002. Epub 2013 Jul 3.
• The discovery of mutated oncogenes has opened up a new era for the development of more effective treatments for non-small cell lung cancer patients (NSCLC) harbouring EGFR mutations. However, patients with EGFR-activating mutation ultimately develop acquired resistance (AR). Several studies have ide
• PMID 23829935

• Radiofrequency ablation suppresses distant tumour growth in a novel rat model of multifocal hepatocellular carcinoma.

• Erös de Bethlenfalva-Hora C, Mertens JC, Piguet AC, Kettenbach J, Schmitt J, Terracciano L, Weimann R, Dufour JF, Geier A.Source*Hepatology, Department of Clinical Research, University of Bern, Bern, Switzerland.
• Clinical science (London, England : 1979).Clin Sci (Lond).2014 Feb;126(3):243-52. doi: 10.1042/CS20130089.
• RFA (radiofrequency ablation) is an established therapy for HCC (hepatocellular carcinoma). The multikinase inhibitor sorafenib prolongs survival in advanced HCC. We examined the effects of RFA alone and in combination with sorafenib on a bystanding tumour in a two-tumour rat model of HCC. A total o
• PMID 23822114

Japanese Journal

• Parallel contractile signal transduction pathways activated by receptors for thrombin and epidermal growth factor-urogastrone in guinea pig gastric smooth muscle: blockade by inhibitors of mitogen-activated protein kinase-kinase and phosphatidyl inositol 3'-kinase

• J Pharmacol Exp Ther 285, 325-334, 1998
• NAID 80010229393

• Regulation of Epidermal Growth Factor Receptors in Rat Gastric Mucosa : Effect of Gastric Ulceration

• Journal of pharmacobio-dynamics 14(9), 527-531, 1991-09
• NAID 110003637447

• Regulation of Epidermal Growth Factor Receptors in Rat Gastric Mucosa : Effect of Fasting and Sialoadenectomy

• Journal of pharmacobio-dynamics 14(6), 301-307, 1991-06
• NAID 110003637417

Related Links

• Urogastrone | Define Urogastrone at Dictionary.com

Medical Dictionary urogastrone u·ro·gas·trone (y&oobreve;r'ə-gās'trōn') n. A fluorescent pigment extracted from urine that inhibits gastric secretion and motility. The American Heritage® Stedman's Medical Dictionary Copyright © 2002 ...

• urogastrone - definition of urogastrone in the Medical ...

urogastrone /uro·gas·trone/ (-gas´trōn) a urinary peptide derived from epidermal growth factor, with which it shares substantial homology and similar effects on the stomach. u·ro·gas·trone (y r-g s tr n) n. A fluorescent pigment extracted ...

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