Amphiregulin

AREG
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2RNL
Identifiers
Aliases	AREG, AR, AREGB, CRDGF, SDGF, amphiregulin
External IDs	OMIM: 104640; MGI: 88068; HomoloGene: 1252; GeneCards: AREG; OMA:AREG - orthologs
Gene location (Human) Chr. Chromosome 4 (human) Band 4q13.3 Start 74,445,136 bp End 74,455,005 bp
Gene location (Mouse) Chr. Chromosome 5 (mouse) Band 5 E2|5 44.78 cM Start 91,287,458 bp End 91,296,291 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of urinary bladder right lung gallbladder amniotic fluid placenta upper lobe of left lung rectum left uterine tube lower lobe of lung appendix Top expressed in mucous cell of stomach pyloric antrum duodenum large intestine colon left colon lip epithelium of stomach conjunctival fornix jejunum More reference expression data BioGPS n/a
Gene ontology Molecular function cytokine activity epidermal growth factor receptor binding protein binding growth factor activity Cellular component cytoplasm integral component of membrane endoplasmic reticulum membrane membrane intracellular anatomical structure cell surface ER to Golgi transport vesicle membrane endoplasmic reticulum-Golgi intermediate compartment membrane nucleus Golgi membrane extracellular space extracellular region clathrin-coated vesicle membrane Biological process dichotomous subdivision of terminal units involved in mammary gland duct morphogenesis G protein-coupled receptor signaling pathway response to estradiol epidermal growth factor receptor signaling pathway response to organic cyclic compound cell-cell signaling mammary gland branching involved in thelarche response to peptide hormone response to glucocorticoid mammary gland alveolus development negative regulation of osteoblast differentiation endoplasmic reticulum to Golgi vesicle-mediated transport epithelial cell proliferation involved in mammary gland duct elongation COPII vesicle coating glial cell proliferation response to cAMP positive regulation of phosphorylation cell population proliferation neuron projection development response to hydrogen peroxide positive regulation of peptidyl-tyrosine phosphorylation regulation of signaling receptor activity positive regulation of cell population proliferation MAPK cascade signal transduction negative regulation of epidermal growth factor receptor signaling pathway positive regulation of protein kinase B signaling membrane organization positive regulation of keratinocyte proliferation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 374 11839 Ensembl ENSG00000109321 ENSMUSG00000029378 UniProt P15514 P31955 RefSeq (mRNA) NM_001657 NM_009704 RefSeq (protein) NP_001648 NP_033834 Location (UCSC) Chr 4: 74.45 – 74.46 Mb Chr 5: 91.29 – 91.3 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Amphiregulin, also known as AREG, is a protein that in humans is encoded by the AREG gene.

Function

The protein encoded by this gene is a member of the epidermal growth factor (EGF) family.

It is an autocrine growth factor as well as a mitogen for astrocytes, Schwann cells, fibroblasts. It is related to epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha). This protein interacts with the Epidermal growth factor receptor (EGFR) to promote the growth of normal epithelial cells.

Biological role

Estradiol and progesterone mostly induce amphiregulin expression to mediate ductal development of the mammary glands. Amphiregulin has been found to be essential for mammary ductal development, as evidenced by absence of ductal growth in amphiregulin knockout mice. This is similar to the phenotypes of EGFR and ERα knockout mice, which also show absence of ductal growth.

Clinical significance

Mutations in this encoded protein are associated with a psoriasis-like skin phenotype.

External links

• Human AR genome location and AR gene details page in the UCSC Genome Browser.
• Human AREG genome location and AREG gene details page in the UCSC Genome Browser.

Further reading

• Culouscou JM, Remacle-Bonnet M, Carlton GW, et al. (1993). "Colorectum cell-derived growth factor (CRDGF) is homologous to amphiregulin, a member of the epidermal growth factor family". Growth Factors. 7 (3): 195–205. doi:10.3109/08977199209046924. PMID 1333777.
• Cook PW, Mattox PA, Keeble WW, et al. (1991). "A heparin sulfate-regulated human keratinocyte autocrine factor is similar or identical to amphiregulin". Molecular and Cellular Biology. 11 (5): 2547–57. PMC 360024. PMID 2017164.
• Kimura H, Fischer WH, Schubert D (1990). "Structure, expression and function of a schwannoma-derived growth factor". Nature. 348 (6298): 257–60. doi:10.1038/348257a0. PMID 2234093.
• Plowman GD, Green JM, McDonald VL, et al. (1990). "The amphiregulin gene encodes a novel epidermal growth factor-related protein with tumor-inhibitory activity". Molecular and Cellular Biology. 10 (5): 1969–81. PMC 360543. PMID 2325643.
• Shoyab M, Plowman GD, McDonald VL, et al. (1989). "Structure and function of human amphiregulin: a member of the epidermal growth factor family". Science. 243 (4894 Pt 1): 1074–6. doi:10.1126/science.2466334. PMID 2466334.
• Shoyab M, McDonald VL, Bradley JG, Todaro GJ (1988). "Amphiregulin: a bifunctional growth-modulating glycoprotein produced by the phorbol 12-myristate 13-acetate-treated human breast adenocarcinoma cell line MCF-7". Proceedings of the National Academy of Sciences of the United States of America. 85 (17): 6528–32. doi:10.1073/pnas.85.17.6528. PMC 282006. PMID 3413110.
• Chen CS, Bejcek BE, Kersey JH (1995). "A mapping study of 13 genes on human chromosome bands 4q11→q25". Cytogenetics and Cell Genetics. 69 (3–4): 260–5. doi:10.1159/000133976. PMID 7698025.
• Cook PW, Piepkorn M, Clegg CH, et al. (1997). "Transgenic expression of the human amphiregulin gene induces a psoriasis-like phenotype". Journal of Clinical Investigation. 100 (9): 2286–94. doi:10.1172/JCI119766. PMC 508424. PMID 9410906.
• Wong L, Deb TB, Thompson SA, et al. (1999). "A differential requirement for the COOH-terminal region of the epidermal growth factor (EGF) receptor in amphiregulin and EGF mitogenic signaling". Journal of Biological Chemistry. 274 (13): 8900–9. doi:10.1074/jbc.274.13.8900. PMID 10085134.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• Reddy KB, Krueger JS, Kondapaka SB, Diglio CA (1999). "Mitogen-activated protein kinase (MAPK) regulates the expression of progelatinase B (MMP-9) in breast epithelial cells". International Journal of Cancer. 82 (2): 268–73. doi:10.1002/(SICI)1097-0215(19990719)82:2<268::AID-IJC18>3.0.CO;2-4. PMID 10389762.
• Fernandes AM, Hamburger AW, Gerwin BI (1999). "Production of epidermal growth factor related ligands in tumorigenic and benign human lung epithelial cells". Cancer Letters. 142 (1): 55–63. doi:10.1016/S0304-3835(99)00166-4. PMID 10424781.
• Lee SB, Huang K, Palmer R, et al. (1999). "The Wilms tumor suppressor WT1 encodes a transcriptional activator of amphiregulin". Cell. 98 (5): 663–73. doi:10.1016/S0092-8674(00)80053-7. PMID 10490105.
• Tokumaru S, Higashiyama S, Endo T, et al. (2000). "Ectodomain Shedding of Epidermal Growth Factor Receptor Ligands Is Required for Keratinocyte Migration in Cutaneous Wound Healing". Journal of Cell Biology. 151 (2): 209–20. doi:10.1083/jcb.151.2.209. PMC 2192647. PMID 11038170.
• Ebert MP, Hernberg S, Fei G, et al. (2001). "Induction and expression of cyclin D3 in human pancreatic cancer". Journal of Cancer Research and Clinical Oncology. 127 (7): 449–54. doi:10.1007/s004320100235. PMID 11469683.
• Berquin IM, Dziubinski ML, Nolan GP, Ethier SP (2001). "A functional screen for genes inducing epidermal growth factor autonomy of human mammary epithelial cells confirms the role of amphiregulin". Oncogene. 20 (30): 4019–28. doi:10.1038/sj.onc.1204537. PMID 11494130.
• Thøgersen VB, Sørensen BS, Poulsen SS, et al. (2001). "A subclass of HER1 ligands are prognostic markers for survival in bladder cancer patients". Cancer Research. 61 (16): 6227–33. PMID 11507076.
• Wolfgang CD, Essand M, Lee B, Pastan I (2001). "T-cell receptor gamma chain alternate reading frame protein (TARP) expression in prostate cancer cells leads to an increased growth rate and induction of caveolins and amphiregulin". Cancer Research. 61 (22): 8122–6. PMID 11719440.
• Schiemann U, Konturek J, Assert R, et al. (2002). "mRNA expression of EGF receptor ligands in atrophic gastritis before and after Helicobacter pylori eradication". Medical Science Monitor. 8 (2): CR53–8. PMID 11859273.
• Tørring N, Møller-Ernst Jensen K, Lund L, et al. (2002). "Possible autocrine loop of the epidermal growth factor system in patients with benign prostatic hyperplasia treated with finasteride: a placebo-controlled randomized study". BJU International. 89 (6): 583–90. doi:10.1046/j.1464-410X.2002.02665.x. PMID 11942969.
• Hurbin A, Dubrez L, Coll JL, Favrot MC (2003). "Inhibition of apoptosis by amphiregulin via an insulin-like growth factor-1 receptor-dependent pathway in non-small cell lung cancer cell lines". Journal of Biological Chemistry. 277 (51): 49127–33. doi:10.1074/jbc.M207584200. PMID 12356750.{{cite journal}}: CS1 maint: unflagged free DOI (link)