Epiregulin Explained

Epiregulin (EPR) is a protein that in humans is encoded by the EREG gene.^{[1] [2]}

Structure

Epiregulin consists of 46 amino acid residues. Its secondary structure contains approximately 30 percent of β-sheet in the strand.^[3] Some of the residues form loops and turns due to the hydrogen bonding.^[3] The percentage of β-sheet in epiregulin depends on the domain and the secondary structures that they occupy. The polymeric molecules of epiregulin has the formula weight of 5280.1 g/mol with a polypeptide(L), a polymer type.^[3]

Structural motifs in most proteins have typical connections in an all β motif. Meaning that the polypeptide chains do not make a crossover connection or in so far as this type of connection has not been observed. Epiregulin is one of the proteins that occupies a typical connection in all β motif. Furthermore, as the structure of epiregulin forms a chain in an all β motif, it also forms β hairpin structural motif. A β hairpin is when the two adjacent anti-parallel β strands connected by a β-turn.

Function

Epiregulin is a member of the epidermal growth factor family. Epiregulin can function as a ligand of epidermal growth factor receptor (EGFR), as well as a ligand of most members of the ERBB (v-erb-b2 oncogene homolog) family of tyrosine-kinase receptors.^[2] The secondary structure at the C-terminus epiregulin is different from other epidermal growth factor family ligands because of the lack of hydrogen bonds. The structural difference at the C-terminus may provide an explanation for the reduced binding affinity of epiregulin to the ERBB receptors.^[3]

Further reading

• Yamamoto T, Akisue T, Marui T . Expression of betacellulin, heparin-binding epidermal growth factor and epiregulin in human malignant fibrous histiocytoma. . Anticancer Res. . 24 . 3b . 2007–10 . 2004. 15274392 . etal.
• Li S, Takeuchi F, Wang JA . Mesenchymal-epithelial interactions involving epiregulin in tuberous sclerosis complex hamartomas. . Proc. Natl. Acad. Sci. U.S.A. . 105 . 9 . 3539–44 . 2008 . 18292222 . 10.1073/pnas.0712397105 . 2265180. 2008PNAS..105.3539L . etal. free .
• Cho MC, Choi HS, Lee S . Epiregulin expression by Ets-1 and ERK signaling pathway in Ki-ras-transformed cells. . Biochem. Biophys. Res. Commun. . 377 . 3 . 832–7 . 2008 . 18948081 . 10.1016/j.bbrc.2008.10.053 . etal.
• Lindvall C, Hou M, Komurasaki T . Molecular characterization of human telomerase reverse transcriptase-immortalized human fibroblasts by gene expression profiling: activation of the epiregulin gene. . Cancer Res. . 63 . 8 . 1743–7 . 2003 . 12702554 . etal.
• Morita S, Shirakata Y, Shiraishi A . Human corneal epithelial cell proliferation by epiregulin and its cross-induction by other EGF family members. . Mol. Vis. . 13 . 2119–28 . 2007 . 18079685 . etal.
• Freimann S, Ben-Ami I, Dantes A . EGF-like factor epiregulin and amphiregulin expression is regulated by gonadotropins/cAMP in human ovarian follicular cells. . Biochem. Biophys. Res. Commun. . 324 . 2 . 829–34 . 2004 . 15474502 . 10.1016/j.bbrc.2004.09.129 . etal.
• Ben-Ami I, Armon L, Freimann S . EGF-like growth factors as LH mediators in the human corpus luteum. . Hum. Reprod. . 24 . 1 . 176–84 . 2009 . 18835871 . 10.1093/humrep/den359 . etal.
• Shigeishi H, Higashikawa K, Hiraoka M . Expression of epiregulin, a novel epidermal growth factor ligand associated with prognosis in human oral squamous cell carcinomas. . Oncol. Rep. . 19 . 6 . 1557–64 . 2008 . 18497965 . 10.3892/or.19.6.1557. etal. free .
• Taylor DS, Cheng X, Pawlowski JE . Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin. . Proc. Natl. Acad. Sci. U.S.A. . 96 . 4 . 1633–8 . 1999 . 9990076 . 10.1073/pnas.96.4.1633 . 15542. 1999PNAS...96.1633T . etal. free .
• Zhang J, Iwanaga K, Choi KC . Intratumoral epiregulin is a marker of advanced disease in non-small cell lung cancer patients and confers invasive properties on EGFR-mutant cells. . Cancer Prev Res (Phila) . 1 . 3 . 201–7 . 2008 . 19138957 . 10.1158/1940-6207.CAPR-08-0014 . 3375599. etal.
• Draper BK, Komurasaki T, Davidson MK, Nanney LB . Epiregulin is more potent than EGF or TGFalpha in promoting in vitro wound closure due to enhanced ERK/MAPK activation. . J. Cell. Biochem. . 89 . 6 . 1126–37 . 2003 . 12898511 . 10.1002/jcb.10584 . 24643892 .
• Révillion F, Lhotellier V, Hornez L, Bonneterre J, Peyrat JP . ErbB/HER ligands in human breast cancer, and relationships with their receptors, the bio-pathological features and prognosis . Ann. Oncol. . 19 . 1 . 73–80 . January 2008 . 17962208 . 10.1093/annonc/mdm431 . free .
• Ben-Ami I, Freimann S, Armon L . PGE2 up-regulates EGF-like growth factor biosynthesis in human granulosa cells: new insights into the coordination between PGE2 and LH in ovulation. . Mol. Hum. Reprod. . 12 . 10 . 593–9 . 2006 . 16888076 . 10.1093/molehr/gal068 . etal. free .
• Takahashi M, Hayashi K, Yoshida K . Epiregulin as a major autocrine/paracrine factor released from ERK- and p38MAPK-activated vascular smooth muscle cells. . Circulation . 108 . 20 . 2524–9 . 2003 . 14581411 . 10.1161/01.CIR.0000096482.02567.8C . 8012969 . etal.
• Lasky-Su J, Neale BM, Franke B . Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations. . Am. J. Med. Genet. B Neuropsychiatr. Genet. . 147B . 8 . 1345–54 . 2008 . 18821565 . 10.1002/ajmg.b.30867 . 9493672 . etal.
• Gupta GP, Nguyen DX, Chiang AC . Mediators of vascular remodelling co-opted for sequential steps in lung metastasis. . Nature . 446 . 7137 . 765–70 . 2007 . 17429393 . 10.1038/nature05760 . 2007Natur.446..765G . 4420038 . etal.
• Shirakata Y, Komurasaki T, Toyoda H . Epiregulin, a novel member of the epidermal growth factor family, is an autocrine growth factor in normal human keratinocytes. . J. Biol. Chem. . 275 . 8 . 5748–53 . 2000 . 10681561 . 10.1074/jbc.275.8.5748. etal. free .

Notes and References

1. Toyoda H, Komurasaki T, Uchida D, Morimoto S . Distribution of mRNA for human epiregulin, a differentially expressed member of the epidermal growth factor family . Biochem. J. . 326 . 1. 69–75 . August 1997 . 9337852 . 1218638 . 10.1042/bj3260069.
2. Web site: Entrez Gene: epiregulin.
3. Sato K, Nakamura T, Mizuguchi M, Miura K, Tada M, Aizawa T, Gomi T, Miyamoto K, Kawano K . Solution structure of epiregulin and the effect of its C-terminal domain for receptor binding affinity . FEBS Lett. . 553 . 3 . 232–8 . October 2003 . 14572630 . 10.1016/s0014-5793(03)01005-6. 24761378 .