Amfiregulin

AREG
Available structures PDB Pretraga ortologa: PDBe RCSB List of PDB id codes 2RNL
Identifikatori
Alijasi	AREG
Spoljašnji ID	OMIM: 104640 MGI: 88068 HomoloGene: 1252 GeneCards: AREG
Genska lokacija (miš) Hr. Chromosome 5 (mouse)[1] Band 5 E2|5 44.78 cM Start 91,287,458 bp[1] Kraj 91,296,291 bp[1]
Genska ontologija Molecular function • активност цитокина • epidermal growth factor receptor binding • GO:0001948, GO:0016582 везивање за протеине плазме • активност фактора раста Cellular component • цитоплазма • саставни део мембране • endoplasmic reticulum membrane • мембрана • Intracelularni • површина ћелије • ER to Golgi transport vesicle membrane • endoplasmic reticulum-Golgi intermediate compartment membrane • једро • Golgi membrane • ванћелијски простор • ванћелијска област • 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 • GO:1904578 response to organic cyclic compound • cell-cell signaling • mammary gland branching involved in thelarche • response to peptide hormone • одговор на глукокортикоидни подстицај • 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 • позитивно уређење фосфорилације • cell population proliferation • neuron projection development • реакција на водоник пероксид • positive regulation of peptidyl-tyrosine phosphorylation • regulation of signaling receptor activity • positive regulation of cell population proliferation • MAPK cascade • GO:0072468 Prenos signala • 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
Ortolozi
Vrste	Čovek	Miš
Entrez	374	11839
Ensembl	ENSG00000109321	ENSMUSG00000029378
UniProt	P15514	P31955
RefSeq (mRNA)	NM_001657	NM_009704
RefSeq (protein)	NP_001648	NP_033834
Location (UCSC)	n/a	Chr 5: 91.29 – 91.3 Mb
PubMed search	[2]	[3]
Wikidata
View/Edit Human View/Edit Mouse

Amfiregulin, takođe poznat kao AREG, je protein koji je kod ljudi kodiran AREG genom.^[4][5][6]

Funkcija

Protein kodiran ovim genom je član familije epidermalnih faktora rasta (EGF).^[4]

On je autokrini faktor rasta kao i mitogen za astrocite, Švanove ćelije, fibroblaste. On je srodan sa epidermalnim faktorom rasta (EGF) i transformirajućim faktorom rasta alfa (TGF-alfa). Ovaj protein interaguje sa receptorom epidermalnog faktora rasta (EGFR) i promoviše rast normalnih epitelijalnih ćelija.

Biološka uloga

Estradiol i progesteron uglavnom indukuju izražavanje amfiregulina da bi posrdovao razviće kanala mlečnih žlezda.^{[7][8][9][10][11]} Za amfiregulin je utvrđeno da je esencijalan za razviće mlečnih kanala, što je dokazano odsustvom rasta kanala kod amfiregulinkih nokaut miševa.^[10] To je slično sa fenotipom EGFR i ERα nokaut miševa, koji isto tako pokazuju odsustvo razvića kanala.^[10]

Klinički značaj

Mutacije u kodiranom proteinu su vezane sa psorijazi sličnim fenotipu kože.^[4]

Reference

1. GRCm38: Ensembl release 89: ENSMUSG00000029378 - Ensembl, May 2017
2. „Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine. 
3. „Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine. 
4. „Entrez Gene: AREG amphiregulin (schwannoma-derived growth factor)”. 
5. Shoyab M, Plowman GD, McDonald VL, Bradley JG, Todaro GJ (1989). „Structure and function of human amphiregulin: a member of the epidermal growth factor family”. Science. 243 (4894 Pt 1): 1074—6. PMID 2466334. doi:10.1126/science.2466334. 
6. Plowman GD, Green JM, McDonald VL, Neubauer MG, Disteche CM, Todaro GJ, Shoyab M (1990). „The amphiregulin gene encodes a novel epidermal growth factor-related protein with tumor-inhibitory activity”. Mol. Cell. Biol. 10 (5): 1969—81. PMC 360543 . PMID 2325643. Архивирано из оригинала 24. 05. 2011. г. Приступљено 11. 10. 2016. 
7. Aupperlee MD, Leipprandt JR, Bennett JM, Schwartz RC, Haslam SZ (2013). „Amphiregulin mediates progesterone-induced mammary ductal development during puberty”. Breast Cancer Res. 15 (3): R44. PMC 3738150 . PMID 23705924. doi:10.1186/bcr3431. 
8. LaMarca HL, Rosen JM (2007). „Estrogen regulation of mammary gland development and breast cancer: amphiregulin takes center stage”. Breast Cancer Res. 9 (4): 304. PMC 2206713 . PMID 17659070. doi:10.1186/bcr1740. 
9. Kariagina A, Xie J, Leipprandt JR, Haslam SZ (2010). „Amphiregulin mediates estrogen, progesterone, and EGFR signaling in the normal rat mammary gland and in hormone-dependent rat mammary cancers”. Horm Cancer. 1 (5): 229—44. PMC 3000471 . PMID 21258428. doi:10.1007/s12672-010-0048-0. 
10. McBryan J, Howlin J, Napoletano S, Martin F (2008). „Amphiregulin: role in mammary gland development and breast cancer”. J Mammary Gland Biol Neoplasia. 13 (2): 159—69. PMID 18398673. doi:10.1007/s10911-008-9075-7. 
11. Sternlicht MD, Sunnarborg SW (2008). „The ADAM17-amphiregulin-EGFR axis in mammary development and cancer”. J Mammary Gland Biol Neoplasia. 13 (2): 181—94. PMC 2723838 . PMID 18470483. doi:10.1007/s10911-008-9084-6. 

Literatura

• 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. PMID 1333777. doi:10.3109/08977199209046924. 
• Cook PW, Mattox PA, Keeble WW, et al. (1991). „A heparin sulfate-regulated human keratinocyte autocrine factor is similar or identical to amphiregulin”. Mol. Cell. Biol. 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. PMID 2234093. doi:10.1038/348257a0. 
• Plowman GD, Green JM, McDonald VL, et al. (1990). „The amphiregulin gene encodes a novel epidermal growth factor-related protein with tumor-inhibitory activity”. Mol. Cell. Biol. 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. PMID 2466334. doi:10.1126/science.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”. Proc. Natl. Acad. Sci. U.S.A. 85 (17): 6528—32. PMC 282006 . PMID 3413110. doi:10.1073/pnas.85.17.6528. 
• Chen CS, Bejcek BE, Kersey JH (1995). „A mapping study of 13 genes on human chromosome bands 4q11→q25”. Cytogenet. Cell Genet. 69 (3–4): 260—5. PMID 7698025. doi:10.1159/000133976. 
• Cook PW, Piepkorn M, Clegg CH, et al. (1997). „Transgenic expression of the human amphiregulin gene induces a psoriasis-like phenotype”. J. Clin. Invest. 100 (9): 2286—94. PMC 508424 . PMID 9410906. doi:10.1172/JCI119766. 
• 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”. J. Biol. Chem. 274 (13): 8900—9. PMID 10085134. doi:10.1074/jbc.274.13.8900. 
• 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”. Int. J. Cancer. 82 (2): 268—73. PMID 10389762. doi:10.1002/(SICI)1097-0215(19990719)82:2<268::AID-IJC18>3.0.CO;2-4. 
• Fernandes AM, Hamburger AW, Gerwin BI (1999). „Production of epidermal growth factor related ligands in tumorigenic and benign human lung epithelial cells”. Cancer Lett. 142 (1): 55—63. PMID 10424781. doi:10.1016/S0304-3835(99)00166-4. 
• 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. PMID 10490105. doi:10.1016/S0092-8674(00)80053-7. 
• 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”. J. Cell Biol. 151 (2): 209—20. PMC 2192647 . PMID 11038170. doi:10.1083/jcb.151.2.209. 
• Ebert MP, Hernberg S, Fei G, et al. (2001). „Induction and expression of cyclin D3 in human pancreatic cancer”. J. Cancer Res. Clin. Oncol. 127 (7): 449—54. PMID 11469683. doi:10.1007/s004320100235. 
• 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. PMID 11494130. doi:10.1038/sj.onc.1204537. 
• Thøgersen VB, Sørensen BS, Poulsen SS, et al. (2001). „A subclass of HER1 ligands are prognostic markers for survival in bladder cancer patients”. Cancer Res. 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 Res. 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”. Med. Sci. Monit. 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 Int. 89 (6): 583—90. PMID 11942969. doi:10.1046/j.1464-410X.2002.02665.x. 
• 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”. J. Biol. Chem. 277 (51): 49127—33. PMID 12356750. doi:10.1074/jbc.M207584200.