EREG
Synonyms
Epiregulin, Ep, EREG, EPR, ER, Proepiregulin
Description
Epiregulin (EREG) is a novel family member of EGF-like ligands and have elevated expression in a variety of human cancers. EREG expression promotes tumor progression and metastasis and reduces patient survival. Ligand of the EGF receptor/EGFR and ERBB4. Stimulates EGFR and ERBB4 tyrosine phosphorylation. Contributes to inflammation, wound healing, tissue repair, and oocyte maturation by regulating angiogenesis and vascular remodeling and by stimulating cell proliferation.
KO Status
F1 (+/-)
Drug Information
Drug in clinical trials: 1
Latest Research Phase: Phase 2 Clinical
Drug Name
Code
Phase
Company
Indications
Clinical Trials
TGF-alpha/epiregulin monoclonal antibody
LY-3016859
Phase 2 Clinical
Eli Lilly And Company
Diabetic Neuropathies, Diabetic Nephropathies, Osteoarthritis, Low Back Pain
NCT Number
NCT04529096
NCT04476108
NCT04456686
NCT01774981
NCT01545583
Intervention Type
Drug
Drug
Drug
Drug
Drug
Indications
Chronic Low-back Pain
Diabetic Peripheral Neuropathic Pain
Osteoarthritis
Diabetic Nephropathy
Healthy Volunteers
Study Phase
Phase 2
Phase 2
Phase 2
Phase 1/Phase 2
Phase 1
Recruitment Status
Recruiting
Recruiting
Recruiting
Completed
Completed
References
Title
Authors
Source
Distribution of mRNA for human epiregulin, a differentially expressed member of the epidermal growth factor family
Toyoda H., Komurasaki T., Uchida D., Morimoto S.,
Biochem. J. 326:69-75(1997)
Complete sequencing and characterization of 21,243 full-length human cDNAs
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Sugano S.,
Nat. Genet. 36:40-45(2004)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)
The MGC Project Team,
Genome Res. 14:2121-2127(2004)
Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4
Komurasaki T., Toyoda H., Uchida D., Morimoto S.,
Oncogene 15:2841-2848(1997)
Solution structure of epiregulin and the effect of its C-terminal domain for receptor binding affinity
Sato K., Nakamura T., Mizuguchi M., Miura K., Tada M., Aizawa T., Gomi T., Miyamoto K., Kawano K.,
FEBS Lett. 553:232-238(2003)
Epiregulin: roles in normal physiology and cancer
Riese D.J. II, Cullum R.L.,
Semin. Cell Dev. Biol. 28:49-56(2014)
The consensus coding sequences of human breast and colorectal cancers
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Science 314:268-274(2006)
Distribution of mRNA for human epiregulin, a differentially expressed member of the epidermal growth factor family.
Toyoda H., Komurasaki T., Uchida D., Morimoto S.,
Biochem. J. 326:69-75(1997)
Complete sequencing and characterization of 21,243 full-length human cDNAs.
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Sugano S.,
Nat. Genet. 36:40-45(2004)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
The MGC Project Team,
Genome Res. 14:2121-2127(2004)
Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4.
Komurasaki T., Toyoda H., Uchida D., Morimoto S.,
Oncogene 15:2841-2848(1997)
Solution structure of epiregulin and the effect of its C-terminal domain for receptor binding affinity.
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FEBS Lett. 553:232-238(2003)
Epiregulin: roles in normal physiology and cancer.
Riese D.J. II, Cullum R.L.,
Semin. Cell Dev. Biol. 28:49-56(2014)
The consensus coding sequences of human breast and colorectal cancers.
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Science 314:268-274(2006)
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ERBIN: a basolateral PDZ protein that interacts with the mammalian ERBB2/HER2 receptor.
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All three PACSIN isoforms bind to endocytic proteins and inhibit endocytosis.
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Estrogen receptor-mediated activation of the serum response element in MCF-7 cells through MAPK-dependent phosphorylation of Elk-1.
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Clathrin uncoating: Auxilin comes to life.
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The class II phosphoinositide 3-kinase C2alpha is activated by clathrin and regulates clathrin-mediated membrane trafficking.
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Phosphotyrosines 627 and 659 of Gab1 constitute a bisphosphoryl tyrosine-based activation motif (BTAM) conferring binding and activation of SHP2.
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J Biol Chem 276:24380-24387(2001)
Multiple interactions of auxilin 1 with clathrin and the AP-2 adaptor complex.
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J Biol Chem 276:36131-36138(2001)
HIP1 functions in clathrin-mediated endocytosis through binding to clathrin and adaptor protein 2.
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The huntingtin interacting protein HIP1 is a clathrin and alpha-adaptin-binding protein involved in receptor-mediated endocytosis.
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Clathrin- and AP-2-binding sites in HIP1 uncover a general assembly role for endocytic accessory proteins.
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Unique phosphorylation mechanism of Gab1 using PI 3-kinase as an adaptor protein.
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A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils a role for Grb2 in negative signaling.
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Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors.
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A single motif responsible for ubiquitin recognition and monoubiquitination in endocytic proteins.
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Epsins and Vps27p/Hrs contain ubiquitin-binding domains that function in receptor endocytosis.
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AP-1 as a regulator of cell life and death.
Shaulian E., Karin M.,
Nat Cell Biol 4:E131-6(2002)
Accessory protein recruitment motifs in clathrin-mediated endocytosis.
Brett T.J., Traub L.M., Fremont D.H.,
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A ubiquitin-interacting motif (UIM) is essential for Eps15 and Eps15R ubiquitination.
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Cbl-directed monoubiquitination of CIN85 is involved in regulation of ligand-induced degradation of EGF receptors.
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Proc. Natl. Acad. Sci. U.S.A. 99:12191-12196(2002)
hSpry2 is targeted to the ubiquitin-dependent proteasome pathway by c-Cbl.
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Roles of mitogen-activated protein kinase and phosphoinositide 3'-kinase in ErbB2/ErbB3 coreceptor-mediated heregulin signaling.
Vijapurkar U., Kim M.S., Koland J.G.,
Exp Cell Res 284:291-302(2003)
Molecular characterization of human telomerase reverse transcriptase-immortalized human fibroblasts by gene expression profiling: activation of the epiregulin gene.
Lindvall C., Hou M., Komurasaki T., Zheng C., Henriksson M., Sedivy J.M., Bjorkholm M., Teh B.T., Nordenskjold M., Xu D.,
Cancer Res 63:1743-1747(2003)
Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation.
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Nat Cell Biol 5:461-466(2003)
Ectodomain cleavage of ErbB-4: characterization of the cleavage site and m80 fragment.
Cheng Q.C., Tikhomirov O., Zhou W., Carpenter G.,
J Biol Chem 278:38421-38427(2003)
Sorting nexin 9 participates in clathrin-mediated endocytosis through interactions with the core components.
Lundmark R., Carlsson S.R.,
J. Biol. Chem. 278:46772-46781(2003)
Molecular mechanism for a role of SHP2 in epidermal growth factor receptor signaling.
Agazie Y.M., Hayman M.J.,
Mol Cell Biol 23:7875-7886(2003)
Synaptojanin is recruited by endophilin to promote synaptic vesicle uncoating.
Verstreken P., Koh T.W., Schulze K.L., Zhai R.G., Hiesinger P.R., Zhou Y., Mehta S.Q., Cao Y., Roos J., Bellen H.J.,
Neuron 40:733-748(2003)
Endophilin is required for synaptic vesicle endocytosis by localizing synaptojanin.
Schuske K.R., Richmond J.E., Matthies D.S., Davis W.S., Runz S., Rube D.A., van der Bliek A.M., Jorgensen E.M.,
Neuron 40:749-762(2003)
Roles of Gab1 and SHP2 in paxillin tyrosine dephosphorylation and Src activation in response to epidermal growth factor.
Ren Y., Meng S., Mei L., Zhao Z.J., Jove R., Wu J.,
J Biol Chem 279:8497-8505(2004)
Distinct domains in the SHP-2 phosphatase differentially regulate epidermal growth factor receptor/NF-kappaB activation through Gab1 in glioblastoma cells.
Kapoor G.S., Zhan Y., Johnson G.R., O'Rourke D.M.,
Mol Cell Biol 24:823-836(2004)
Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment.
Zhang S.Q., Yang W., Kontaridis M.I., Bivona T.G., Wen G., Araki T., Luo J., Thompson J.A., Schraven B.L., Philips M.R., Neel B.G.,
Mol. Cell 13:341-355(2004)
Analysis of clathrin-mediated endocytosis of epidermal growth factor receptor by RNA interference.
Huang F., Khvorova A., Marshall W., Sorkin A.,
J. Biol. Chem. 279:16657-16661(2004)
Role of protein ubiquitylation in regulating endocytosis of receptor tyrosine kinases.
Marmor M.D., Yarden Y.,
Oncogene 23:2057-2070(2004)
The G protein-coupled receptor GPR30 mediates c-fos up-regulation by 17beta-estradiol and phytoestrogens in breast cancer cells.
Maggiolini M., Vivacqua A., Fasanella G., Recchia A.G., Sisci D., Pezzi V., Montanaro D., Musti A.M., Picard D., Ando S.,
J Biol Chem 279:27008-27016(2004)
Regulation of ubiquitin protein ligase activity in c-Cbl by phosphorylation-induced conformational change and constitutive activation by tyrosine to glutamate point mutations.
Kassenbrock C.K., Anderson S.M.,
J Biol Chem 279:28017-28027(2004)
Memo mediates ErbB2-driven cell motility.
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Ligand regulates epidermal growth factor receptor kinase specificity: activation increases preference for GAB1 and SHC versus autophosphorylation sites.
Fan Y.X., Wong L., Deb T.B., Johnson G.R.,
J Biol Chem 279:38143-38150(2004)
A novel dynamin-associating molecule, formin-binding protein 17, induces tubular membrane invaginations and participates in endocytosis.
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Dap160/intersectin scaffolds the periactive zone to achieve high-fidelity endocytosis and normal synaptic growth.
Marie B., Sweeney S.T., Poskanzer K.E., Roos J., Kelly R.B., Davis G.W.,
Neuron 43:207-219(2004)
Expression of betacellulin, heparin-binding epidermal growth factor and epiregulin in human malignant fibrous histiocytoma.
Yamamoto T., Akisue T., Marui T., Nakatani T., Kawamoto T., Hitora T., Nagira K., Fujita I., Matsumoto K., Kurosaka M.,
Anticancer Res 24:2007-2010(2004)
The stimulatory action of amphiphysin on dynamin function is dependent on lipid bilayer curvature.
Yoshida Y., Kinuta M., Abe T., Liang S., Araki K., Cremona O., Di Paolo G., Moriyama Y., Yasuda T., De Camilli P., Takei K.,
EMBO J 23:3483-3491(2004)
Ubiquitin ligase activity of c-Cbl guides the epidermal growth factor receptor into clathrin-coated pits by two distinct modes of Eps15 recruitment.
de Melker A.A., van der Horst G., Borst J.,
J Biol Chem 279:55465-55473(2004)
EGF-like factor epiregulin and amphiregulin expression is regulated by gonadotropins/cAMP in human ovarian follicular cells.
Freimann S., Ben-Ami I., Dantes A., Ron-El R., Amsterdam A.,
Biochem Biophys Res Commun 324:829-834(2004)
Direct interaction of Cbl with pTyr 1045 of the EGF receptor (EGFR) is required to sort the EGFR to lysosomes for degradation.
Grovdal L.M., Stang E., Sorkin A., Madshus I.H.,
Exp Cell Res 300:388-395(2004)
Molecular model for a complete clathrin lattice from electron cryomicroscopy.
Fotin A., Cheng Y., Sliz P., Grigorieff N., Harrison S.C., Kirchhausen T., Walz T.,
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Structure of an auxilin-bound clathrin coat and its implications for the mechanism of uncoating.
Fotin A., Cheng Y., Grigorieff N., Walz T., Harrison S.C., Kirchhausen T.,
Nature 432:649-653(2004)
AP-1 subunits: quarrel and harmony among siblings.
Hess J., Angel P., Schorpp-Kistner M.,
J Cell Sci 117:5965-5973(2004)
Hsp90 restrains ErbB-2/HER2 signalling by limiting heterodimer formation.
Citri A., Gan J., Mosesson Y., Vereb G., Szollosi J., Yarden Y.,
EMBO Rep 5:1165-1170(2004)
A novel role for Gab1 and SHP2 in epidermal growth factor-induced Ras activation.
Montagner A., Yart A., Dance M., Perret B., Salles J.P., Raynal P.,
J Biol Chem 280:5350-5360(2005)
Surface charge and hydrophobicity determine ErbB2 binding to the Hsp90 chaperone complex.
Xu W., Yuan X., Xiang Z., Mimnaugh E., Marcu M., Neckers L.,
Nat Struct Mol Biol 12:120-126(2005)
BAR domains and membrane curvature: bringing your curves to the BAR.
Gallop J.L., McMahon H.T.,
Biochem Soc Symp 2005:223-231(2005)
Phosphotyrosine signaling networks in epidermal growth factor receptor overexpressing squamous carcinoma cells.
Thelemann A., Petti F., Griffin G., Iwata K., Hunt T., Settinari T., Fenyo D., Gibson N., Haley J.D.,
Mol Cell Proteomics 4:356-376(2005)
Clathrin-independent endocytosis of ubiquitinated cargos.
Sigismund S., Woelk T., Puri C., Maspero E., Tacchetti C., Transidico P., Di Fiore P.P., Polo S.,
Proc Natl Acad Sci U S A 102:2760-2765(2005)
SNX9 regulates dynamin assembly and is required for efficient clathrin-mediated endocytosis.
Soulet F., Yarar D., Leonard M., Schmid S.L.,
Mol. Biol. Cell 16:2058-2067(2005)
PI 3-kinase p110beta: a new target for antithrombotic therapy.
Jackson S.P., Schoenwaelder S.M., Goncalves I., Nesbitt W.S., Yap C.L., Wright C.E., Kenche V., Anderson K.E., Dopheide S.M., Yuan Y., Sturgeon S.A., Prabaharan H., Thompson P.E., Smith G.D., Shepherd P.R., Daniele N., Kulkarni S., Abbott B., Salem H.H.,
Nat Med 11:507-514(2005)
Caenorhabditis elegans RME-6 is a novel regulator of RAB-5 at the clathrin-coated pit.
Sato M., Sato K., Fonarev P., Huang C.-J., Liou W., Grant B.D.,
Nat. Cell Biol. 7:559-569(2005)
Sprouty2 acts at the Cbl/CIN85 interface to inhibit epidermal growth factor receptor downregulation.
Haglund K., Schmidt M.H., Wong E.S., Guy G.R., Dikic I.,
EMBO Rep. 6:635-641(2005)
An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway.
Shin H.W., Hayashi M., Christoforidis S., Lacas-Gervais S., Hoepfner S., Wenk M.R., Modregger J., Uttenweiler-Joseph S., Wilm M., Nystuen A., Frankel W.N., Solimena M., De Camilli P., Zerial M.,
J Cell Biol 170:607-618(2005)
The Fos family of transcription factors and their role in tumourigenesis.
Milde-Langosch K.,
Eur J Cancer 41:2449-2461(2005)
Individual phosphoinositide 3-kinase C2alpha domain activities independently regulate clathrin function.
Gaidarov I., Zhao Y., Keen J.H.,
J. Biol. Chem. 280:40766-40772(2005)
The G protein-coupled receptor GPR30 mediates the proliferative effects induced by 17beta-estradiol and hydroxytamoxifen in endometrial cancer cells.
Vivacqua A., Bonofiglio D., Recchia A.G., Musti A.M., Picard D., Ando S., Maggiolini M.,
Mol Endocrinol 20:631-646(2006)
Dynamin and the actin cytoskeleton cooperatively regulate plasma membrane invagination by BAR and F-BAR proteins.
Itoh T., Erdmann K.S., Roux A., Habermann B., Werner H., De Camilli P.,
Dev. Cell 9:791-804(2005)
Cbl escapes Cdc42-mediated inhibition by downregulation of the adaptor molecule betaPix.
Schmidt M.H.H., Husnjak K., Szymkiewicz I., Haglund K., Dikic I.,
Oncogene 25:3071-3078(2006)
Rab5-activating protein 6, a novel endosomal protein with a role in endocytosis.
Hunker C.M., Galvis A., Kruk I., Giambini H., Veisaga M.L., Barbieri M.A.,
Biochem. Biophys. Res. Commun. 340:967-975(2006)
Molecular switches involving the AP-2 beta2 appendage regulate endocytic cargo selection and clathrin coat assembly.
Edeling M.A., Mishra S.K., Keyel P.A., Steinhauser A.L., Collins B.M., Roth R., Heuser J.E., Owen D.J., Traub L.M.,
Dev. Cell 10:329-342(2006)
A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling.
Knight Z.A., Gonzalez B., Feldman M.E., Zunder E.R., Goldenberg D.D., Williams O., Loewith R., Stokoe D., Balla A., Toth B., Balla T., Weiss W.A., Williams R.L., Shokat K.M.,
Cell 125:733-747(2006)
A burst of auxilin recruitment determines the onset of clathrin-coated vesicle uncoating.
Massol R.H., Boll W., Griffin A.M., Kirchhausen T.,
Proc Natl Acad Sci U S A 103:10265-10270(2006)
17beta-estradiol, genistein, and 4-hydroxytamoxifen induce the proliferation of thyroid cancer cells through the g protein-coupled receptor GPR30.
Vivacqua A., Bonofiglio D., Albanito L., Madeo A., Rago V., Carpino A., Musti A.M., Picard D., Ando S., Maggiolini M.,
Mol Pharmacol 70:1414-1423(2006)
HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors.
Wang S.E., Narasanna A., Perez-Torres M., Xiang B., Wu F.Y., Yang S., Carpenter G., Gazdar A.F., Muthuswamy S.K., Arteaga C.L.,
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