Ephrin B2 Explained

Ephrin-B2 is a protein that in humans is encoded by the EFNB2 gene.^[1]

Function

This gene encodes a member of the ephrin (EPH) family. The ephrins and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, especially in the nervous system and in erythropoiesis. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. This gene encodes an EFNB class ephrin which binds to the EPHB4 and EPHA3 receptors.^[2]

Cancer

EFNB2 gene has been observed progressively downregulated in Human papillomavirus-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy.^[3] For this reason, EFNB2 is likely to be associated with tumorigenesis and may be a potential prognostic marker for uterine cervical preneoplastic lesions progression.^[3]

Interactions

EFNB2 has been shown to interact with EPHA3^{[4] [5]} and EPHB1 in optic chiasm development.^[6]

EFNB2 has also been shown to serve as a receptor for Hendra Virus and Nipah Virus, mediating entry into the cell during infection.^[7]

Further reading

• Flanagan JG, Vanderhaeghen P . The ephrins and Eph receptors in neural development . Annual Review of Neuroscience . 21 . 309–45 . 1998 . 9530499 . 10.1146/annurev.neuro.21.1.309 .
• Zhou R . The Eph family receptors and ligands . Pharmacology & Therapeutics . 77 . 3 . 151–81 . Mar 1998 . 9576626 . 10.1016/S0163-7258(97)00112-5 .
• Holder N, Klein R . Eph receptors and ephrins: effectors of morphogenesis . Development . 126 . 10 . 2033–44 . May 1999 . 10.1242/dev.126.10.2033 . 10207129 .
• Wilkinson DG . Eph receptors and ephrins: regulators of guidance and assembly . International Review of Cytology . 196 . 177–244 . 2000 . 10730216 . 10.1016/S0074-7696(00)96005-4 . 9780123646002 .
• Xu Q, Mellitzer G, Wilkinson DG . Roles of Eph receptors and ephrins in segmental patterning . Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences . 355 . 1399 . 993–1002 . Jul 2000 . 11128993 . 1692797 . 10.1098/rstb.2000.0635 .
• Wilkinson DG . Multiple roles of EPH receptors and ephrins in neural development . Nature Reviews. Neuroscience . 2 . 3 . 155–64 . Mar 2001 . 11256076 . 10.1038/35058515 . 205014301 .
• Bennett BD, Zeigler FC, Gu Q, Fendly B, Goddard AD, Gillett N, Matthews W . Molecular cloning of a ligand for the EPH-related receptor protein-tyrosine kinase Htk . Proceedings of the National Academy of Sciences of the United States of America . 92 . 6 . 1866–70 . Mar 1995 . 7534404 . 42383 . 10.1073/pnas.92.6.1866 . 1995PNAS...92.1866B . free .
• Cerretti DP, Vanden Bos T, Nelson N, Kozlosky CJ, Reddy P, Maraskovsky E, Park LS, Lyman SD, Copeland NG, Gilbert DJ . Isolation of LERK-5: a ligand of the eph-related receptor tyrosine kinases . Molecular Immunology . 32 . 16 . 1197–205 . Nov 1995 . 8559144 . 10.1016/0161-5890(95)00108-5 .
• Cerretti DP, Lyman SD, Kozlosky CJ, Copeland NG, Gilbert DJ, Jenkins NA, Valentine V, Kirstein MN, Shapiro DN, Morris SW . The genes encoding the eph-related receptor tyrosine kinase ligands LERK-1 (EPLG1, Epl1), LERK-3 (EPLG3, Epl3), and LERK-4 (EPLG4, Epl4) are clustered on human chromosome 1 and mouse chromosome 3 . Genomics . 33 . 2 . 277–82 . Apr 1996 . 8660976 . 10.1006/geno.1996.0192 .
• Gale NW, Holland SJ, Valenzuela DM, Flenniken A, Pan L, Ryan TE, Henkemeyer M, Strebhardt K, Hirai H, Wilkinson DG, Pawson T, Davis S, Yancopoulos GD . Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis . Neuron . 17 . 1 . 9–19 . Jul 1996 . 8755474 . 10.1016/S0896-6273(00)80276-7 . free .
• Holland SJ, Gale NW, Mbamalu G, Yancopoulos GD, Henkemeyer M, Pawson T . Bidirectional signalling through the EPH-family receptor Nuk and its transmembrane ligands . Nature . 383 . 6602 . 722–5 . Oct 1996 . 8878483 . 10.1038/383722a0 . 1996Natur.383..722H . 1807/9444 . 4349898 . free .
• Ephnomenclaturecommittee . Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph Nomenclature Committee . Cell . 90 . 3 . 403–4 . Aug 1997 . 9267020 . 10.1016/S0092-8674(00)80500-0 . free .
• Vogt T, Stolz W, Welsh J, Jung B, Kerbel RS, Kobayashi H, Landthaler M, McClelland M . Overexpression of Lerk-5/Eplg5 messenger RNA: a novel marker for increased tumorigenicity and metastatic potential in human malignant melanomas . Clinical Cancer Research . 4 . 3 . 791–7 . Mar 1998 . 9533549 .
• Wang HU, Chen ZF, Anderson DJ . Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4 . Cell . 93 . 5 . 741–53 . May 1998 . 9630219 . 10.1016/S0092-8674(00)81436-1 . free .
• Nikolova Z, Djonov V, Zuercher G, Andres AC, Ziemiecki A . Cell-type specific and estrogen dependent expression of the receptor tyrosine kinase EphB4 and its ligand ephrin-B2 during mammary gland morphogenesis . Journal of Cell Science . 111 . 18 . 2741–51 . Sep 1998 . 10.1242/jcs.111.18.2741 . 9718367 .
• Torres R, Firestein BL, Dong H, Staudinger J, Olson EN, Huganir RL, Bredt DS, Gale NW, Yancopoulos GD . PDZ proteins bind, cluster, and synaptically colocalize with Eph receptors and their ephrin ligands . Neuron . 21 . 6 . 1453–63 . Dec 1998 . 9883737 . 10.1016/S0896-6273(00)80663-7 . free .
• Lin D, Gish GD, Songyang Z, Pawson T . The carboxyl terminus of B class ephrins constitutes a PDZ domain binding motif . The Journal of Biological Chemistry . 274 . 6 . 3726–33 . Feb 1999 . 9920925 . 10.1074/jbc.274.6.3726 . free .

Notes and References

1. Bonaldo MF, Yu MT, Jelenc P, Brown S, Su L, Lawton L, Deaven L, Efstratiadis A, Warburton D, Soares MB . Selection of cDNAs using chromosome-specific genomic clones: application to human chromosome 13 . Human Molecular Genetics . 3 . 9 . 1663–73 . Sep 1994 . 7833926 . 10.1093/hmg/3.9.1663 .
2. Web site: Entrez Gene: EFNB2 ephrin-B2.
3. Rotondo JC, Bosi S, Bassi C, Ferracin M, Lanza G, Gafà R, Magri E, Selvatici R, Torresani S, Marci R, Garutti P, Negrini M, Tognon M, Martini F . Gene expression changes in progression of cervical neoplasia revealed by microarray analysis of cervical neoplastic keratinocytes. . J Cell Physiol . 230. 4 . 802–812 . April 2015 . 25205602 . 10.1002/jcp.24808 . 11392/2066612 . 24986454 . free .
4. Cerretti DP, Vanden Bos T, Nelson N, Kozlosky CJ, Reddy P, Maraskovsky E, Park LS, Lyman SD, Copeland NG, Gilbert DJ . Isolation of LERK-5: a ligand of the eph-related receptor tyrosine kinases . Molecular Immunology . 32 . 16 . 1197–205 . Nov 1995 . 8559144 . 10.1016/0161-5890(95)00108-5 .
5. Lackmann M, Mann RJ, Kravets L, Smith FM, Bucci TA, Maxwell KF, Howlett GJ, Olsson JE, Vanden Bos T, Cerretti DP, Boyd AW . Ligand for EPH-related kinase (LERK) 7 is the preferred high affinity ligand for the HEK receptor . The Journal of Biological Chemistry . 272 . 26 . 16521–30 . Jun 1997 . 9195962 . 10.1074/jbc.272.26.16521 . free .
6. Williams SE, Mann F, Erskine L, Sakurai T, Wei S, Rossi DJ, Gale NW, Holt CE, Mason CA, Henkemeyer M . Ephrin-B2 and EphB1 mediate retinal axon divergence at the optic chiasm . Neuron . 39 . 6 . 919–35 . September 2003 . 12971893 . 10.1016/j.neuron.2003.08.017. free .
7. Bonaparte MI, Dimitrov AS, Bossart KN, Crameri G, Mungall BA, Bishop KA, Choudhry V, Dimitrov DS, Wang LF, Eaton BT, Broder CC . Ephrin-B2 ligand is a functional receptor for Hendra virus and Nipah virus . Proceedings of the National Academy of Sciences of the United States of America . 102 . 30 . 10652–7 . July 2005 . 15998730 . 10.1073/pnas.0504887102 . 1169237 . 2005PNAS..10210652B . free .