epha2 receptor


Summary: An Eph family receptor found abundantly in tissues of epithelial origin. It is expressed in a diverse array of tissues during embryonic development, suggesting that it may play a role in embryogenesis. In adult tissues high levels of the receptor are expressed in the LUNG; SKIN; SMALL INTESTINE and OVARY.

Top Publications

  1. Cercone M, Schroeder W, Schomberg S, Carpenter T. EphA2 receptor mediates increased vascular permeability in lung injury due to viral infection and hypoxia. Am J Physiol Lung Cell Mol Physiol. 2009;297:L856-63 pubmed publisher
    ..We found that the EphA2 receptor is expressed in normal lung and that EphA2 expression is markedly upregulated in the lungs of hypoxic infected ..
  2. Carter N, Nakamoto T, Hirai H, Hunter T. EphrinA1-induced cytoskeletal re-organization requires FAK and p130(cas). Nat Cell Biol. 2002;4:565-73 pubmed
    ..actin cytoskeletal changes in fibroblasts in a FAK- and p130(cas)-dependent manner, through activation of the EphA2 receptor. The finding that ephrin Eph signalling can result in actin cytoskeletal assembly, rather than disassembly, ..
  3. Carles Kinch K, Kilpatrick K, Stewart J, Kinch M. Antibody targeting of the EphA2 tyrosine kinase inhibits malignant cell behavior. Cancer Res. 2002;62:2840-7 pubmed
    ..Our studies also emphasize how tumor-specific cellular behaviors can be exploited to identify and screen potential therapeutic targets. ..
  4. Kinch M, Moore M, Harpole D. Predictive value of the EphA2 receptor tyrosine kinase in lung cancer recurrence and survival. Clin Cancer Res. 2003;9:613-8 pubmed
    ..analyses of a retrospective database of pathologic specimens were used to demonstrate that the EphA2 receptor kinase is frequently overexpressed in NSCLC...
  5. Thaker P, Deavers M, Celestino J, Thornton A, Fletcher M, Landen C, et al. EphA2 expression is associated with aggressive features in ovarian carcinoma. Clin Cancer Res. 2004;10:5145-50 pubmed
    ..04) and EphA2 overexpression (P < 0.01) were significant and independent predictors of survival. EphA2 overexpression is predictive of aggressive ovarian cancer behavior and may be an important therapeutic target. ..
  6. Nowakowski J, Cronin C, McRee D, Knuth M, Nelson C, Pavletich N, et al. Structures of the cancer-related Aurora-A, FAK, and EphA2 protein kinases from nanovolume crystallography. Structure. 2002;10:1659-67 pubmed
    ..The FAK and Aurora-A structures are the first determined within two unique subfamilies of human kinases, and all three structures provide new insights into kinase regulation and the design of selective inhibitors. ..
  7. Hunter S, Zhuang G, Brantley Sieders D, Swat W, Cowan C, Chen J. Essential role of Vav family guanine nucleotide exchange factors in EphA receptor-mediated angiogenesis. Mol Cell Biol. 2006;26:4830-42 pubmed
    ..Prior studies from our laboratory demonstrate that the EphA2 receptor tyrosine kinase is a key regulator of angiogenesis in vivo...
  8. Fang W, Brantley Sieders D, Hwang Y, Ham A, Chen J. Identification and functional analysis of phosphorylated tyrosine residues within EphA2 receptor tyrosine kinase. J Biol Chem. 2008;283:16017-26 pubmed publisher
  9. Jun G, Guo H, Klein B, Klein R, Wang J, Mitchell P, et al. EPHA2 is associated with age-related cortical cataract in mice and humans. PLoS Genet. 2009;5:e1000584 pubmed publisher
    ..Thus, converging evidence from humans and mice suggests that EPHA2 is important in maintaining lens clarity with age...

More Information


  1. Miao H, Burnett E, Kinch M, Simon E, Wang B. Activation of EphA2 kinase suppresses integrin function and causes focal-adhesion-kinase dephosphorylation. Nat Cell Biol. 2000;2:62-9 pubmed
    ..We conclude that Eph kinases mediate some of their functions by negatively regulating integrins and FAK. ..
  2. Zhang T, Hua R, Xiao W, Burdon K, Bhattacharya S, Craig J, et al. Mutations of the EPHA2 receptor tyrosine kinase gene cause autosomal dominant congenital cataract. Hum Mutat. 2009;30:E603-11 pubmed publisher
    ..dominant posterior polar CC and total CC have both been mapped to the chromosomal 1p36 region harboring the EPHA2 receptor tyrosine kinase gene. Here, we report mutations of EPHA2 in three CC families from different ancestral groups...
  3. Wykosky J, Debinski W. The EphA2 receptor and ephrinA1 ligand in solid tumors: function and therapeutic targeting. Mol Cancer Res. 2008;6:1795-806 pubmed publisher
    ..This review will specifically focus on the roles that EphA2 and ephrinA1 play in the different cell types that contribute to the malignancy of solid tumors, with emphasis on the opportunities for therapeutic targeting. ..
  4. Pandey A, Lazar D, Saltiel A, Dixit V. Activation of the Eck receptor protein tyrosine kinase stimulates phosphatidylinositol 3-kinase activity. J Biol Chem. 1994;269:30154-7 pubmed
    ..This is the first description of a signal transduction pathway initiated by any member of the Eph/Eck family. ..
  5. Vaught D, Chen J, Brantley Sieders D. Regulation of mammary gland branching morphogenesis by EphA2 receptor tyrosine kinase. Mol Biol Cell. 2009;20:2572-81 pubmed publisher
    ..Using EphA2-deficient animals, we demonstrate for the first time that EphA2 receptor function is required for mammary epithelial growth and branching morphogenesis...
  6. Miao H, Li D, Mukherjee A, Guo H, Petty A, Cutter J, et al. EphA2 mediates ligand-dependent inhibition and ligand-independent promotion of cell migration and invasion via a reciprocal regulatory loop with Akt. Cancer Cell. 2009;16:9-20 pubmed publisher
    ..In human astrocytoma, S897 phosphorylation was correlated with tumor grades and Akt activation, suggesting that the Akt-EphA2 crosstalk may contribute to brain tumor progression. ..
  7. Menges C, McCance D. Constitutive activation of the Raf-MAPK pathway causes negative feedback inhibition of Ras-PI3K-AKT and cellular arrest through the EphA2 receptor. Oncogene. 2008;27:2934-40 pubmed
  8. Zhuang G, Hunter S, Hwang Y, Chen J. Regulation of EphA2 receptor endocytosis by SHIP2 lipid phosphatase via phosphatidylinositol 3-Kinase-dependent Rac1 activation. J Biol Chem. 2007;282:2683-94 pubmed
    ..In particular, ephrin-A ligand stimulation of tumor cells induces EphA2 receptor internalization and degradation, a process that has been explored as a means to reduce tumor malignancy...
  9. Landen C, Chavez Reyes A, Bucana C, Schmandt R, Deavers M, Lopez Berestein G, et al. Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery. Cancer Res. 2005;65:6910-8 pubmed
    ..04 versus 0.22 g; P < 0.001; HeyA8: 0.21 versus 0.84 g; P = 0.0027). These studies show the feasibility of siRNA as a clinically applicable therapeutic modality. ..
  10. Mitra S, Duggineni S, Koolpe M, Zhu X, Huang Z, Pasquale E. Structure-activity relationship analysis of peptides targeting the EphA2 receptor. Biochemistry. 2010;49:6687-95 pubmed publisher
    The EphA2 receptor tyrosine kinase has emerged as a promising new therapeutic target in cancer because of its high level of expression in tumors...
  11. Wang Y, Ota S, Kataoka H, Kanamori M, Li Z, Band H, et al. Negative regulation of EphA2 receptor by Cbl. Biochem Biophys Res Commun. 2002;296:214-20 pubmed
    ..These results demonstrate that the TKB domain and RING finger domain of Cbl are essential for this negative regulation. ..
  12. Macrae M, Neve R, Rodriguez Viciana P, Haqq C, Yeh J, Chen C, et al. A conditional feedback loop regulates Ras activity through EphA2. Cancer Cell. 2005;8:111-8 pubmed
    The EphA2 receptor tyrosine kinase is frequently overexpressed in many cancers, including 40% of breast cancers...
  13. Brittis P, Lu Q, Flanagan J. Axonal protein synthesis provides a mechanism for localized regulation at an intermediate target. Cell. 2002;110:223-35 pubmed
    ..These results show axons contain all the machinery for protein translation and cell surface expression, and they reveal a potentially general and flexible RNA-based mechanism for regulation localized within a subregion of the axon. ..
  14. Brantley Sieders D, Zhuang G, Hicks D, Fang W, Hwang Y, Cates J, et al. The receptor tyrosine kinase EphA2 promotes mammary adenocarcinoma tumorigenesis and metastatic progression in mice by amplifying ErbB2 signaling. J Clin Invest. 2008;118:64-78 pubmed
    ..Moreover, EphA2 function in tumor progression appeared to depend on oncogene context, an important consideration for the application of therapies targeting EphA2...
  15. Fang W, Ireton R, Zhuang G, Takahashi T, Reynolds A, Chen J. Overexpression of EPHA2 receptor destabilizes adherens junctions via a RhoA-dependent mechanism. J Cell Sci. 2008;121:358-68 pubmed publisher
    b>EPHA2 receptor tyrosine kinase is overexpressed in several human cancer types and promotes malignancy. However, the mechanisms by which EPHA2 promotes tumor progression are not completely understood...
  16. Landen C, Lu C, Han L, Coffman K, Bruckheimer E, Halder J, et al. Efficacy and antivascular effects of EphA2 reduction with an agonistic antibody in ovarian cancer. J Natl Cancer Inst. 2006;98:1558-70 pubmed
    ..Humanized antibody constructs against EphA2 are worthy of future study. ..
  17. Wykosky J, Palma E, Gibo D, Ringler S, Turner C, Debinski W. Soluble monomeric EphrinA1 is released from tumor cells and is a functional ligand for the EphA2 receptor. Oncogene. 2008;27:7260-73 pubmed publisher
    The ephrinA1 ligand exerts antioncogenic effects in tumor cells through activation and downregulation of the EphA2 receptor and has been described as a membrane-anchored protein requiring clustering for function...
  18. Kiewlich D, Zhang J, Gross C, Xia W, Larsen B, Cobb R, et al. Anti-EphA2 antibodies decrease EphA2 protein levels in murine CT26 colorectal and human MDA-231 breast tumors but do not inhibit tumor growth. Neoplasia. 2006;8:18-30 pubmed
    The EphA2 receptor tyrosine kinase has been shown to be over-expressed in cancer and a monoclonal antibody (mAb) that activates and down-modulates EphA2 was reported to inhibit the growth of human breast and lung tumor xenografts in nude ..
  19. Chen J, Hicks D, Brantley Sieders D, Cheng N, McCollum G, Qi Werdich X, et al. Inhibition of retinal neovascularization by soluble EphA2 receptor. Exp Eye Res. 2006;82:664-73 pubmed
    ..Since EphA2-Fc receptors can inhibit activation of multiple EphA receptors, the specific role of EphA2 receptor in angiogenesis was further investigated in EphA2-deficient endothelial cells...
  20. Eustace A, Crown J, Clynes M, O Donovan N. Preclinical evaluation of dasatinib, a potent Src kinase inhibitor, in melanoma cell lines. J Transl Med. 2008;6:53 pubmed publisher
    ..Dasatinib has both anti-proliferative and anti-invasive effects in melanoma cells and combined with chemotherapy may have clinical benefit in the treatment of malignant melanoma. ..
  21. Leone M, Cellitti J, Pellecchia M. NMR studies of a heterotypic Sam-Sam domain association: the interaction between the lipid phosphatase Ship2 and the EphA2 receptor. Biochemistry. 2008;47:12721-8 pubmed publisher
    ..It has been recently reported that the lipid phosphatase Ship2 regulates endocytosis of the EphA2 receptor, a process that has been investigated as a possible route to reduce tumor malignancy...
  22. Ireton R, Chen J. EphA2 receptor tyrosine kinase as a promising target for cancer therapeutics. Curr Cancer Drug Targets. 2005;5:149-57 pubmed
    ..This review focuses on the multiple roles of EphA2 in cancer progression, the mechanisms by which EphA2 inhibition may halt this progression, and the pre-clinical results of EphA2 inhibition in various cancer model systems. ..
  23. Duxbury M, Ito H, Zinner M, Ashley S, Whang E. Ligation of EphA2 by Ephrin A1-Fc inhibits pancreatic adenocarcinoma cellular invasiveness. Biochem Biophys Res Commun. 2004;320:1096-102 pubmed
    ..EphA2 appears to represent a rational therapeutic target and ligation by Ephrin A1-Fc is one strategy to modulate levels of this oncoprotein. ..
  24. Bogan C, Chen J, O Sullivan M, Cormier R. Loss of EphA2 receptor tyrosine kinase reduces ApcMin/+ tumorigenesis. Int J Cancer. 2009;124:1366-71 pubmed publisher
    ..Overall, our results indicate that EphA2 plays an oncogenic role in the mammalian intestine suggesting that strategies to target EphA2 activity may offer new therapeutic modalities for colorectal cancer. ..
  25. Naruse Nakajima C, Asano M, Iwakura Y. Involvement of EphA2 in the formation of the tail notochord via interaction with ephrinA1. Mech Dev. 2001;102:95-105 pubmed
    ..These observations suggest that EphA2 and its ligands are involved in the positioning of the tail notochord through repulsive signals between cells expressing these molecules on the surface. ..
  26. Zelinski D, Zantek N, Stewart J, Irizarry A, Kinch M. EphA2 overexpression causes tumorigenesis of mammary epithelial cells. Cancer Res. 2001;61:2301-6 pubmed
    ..Interestingly, stimulation of EphA2 reverses the malignant growth and invasiveness of EphA2-transformed cells. Taken together, these results identify EphA2 as a powerful oncoprotein in breast cancer. ..
  27. Easty D, Hill S, Hsu M, Fallowfield M, Florenes V, Herlyn M, et al. Up-regulation of ephrin-A1 during melanoma progression. Int J Cancer. 1999;84:494-501 pubmed
    ..Both effects may be potentiated by inflammatory responses. Our data are consistent with earlier observations that an inflammatory infiltrate is associated with poor prognosis in thin primary melanomas. ..
  28. Walker Daniels J, Riese D, Kinch M. c-Cbl-dependent EphA2 protein degradation is induced by ligand binding. Mol Cancer Res. 2002;1:79-87 pubmed
    The EphA2 receptor protein tyrosine kinase is overexpressed and functionally altered in a large number of human carcinomas...
  29. Cooper M, Son A, Komlos D, Sun Y, Kleiman N, Zhou R. Loss of ephrin-A5 function disrupts lens fiber cell packing and leads to cataract. Proc Natl Acad Sci U S A. 2008;105:16620-5 pubmed publisher
    ..We further demonstrate that ephrin-A5 interacts with the EphA2 receptor to regulate the adherens junction complex by enhancing recruitment of beta-catenin to N-cadherin...
  30. Shao H, Pandey A, O Shea K, Seldin M, Dixit V. Characterization of B61, the ligand for the Eck receptor protein-tyrosine kinase. J Biol Chem. 1995;270:5636-41 pubmed
    ..Finally, the gene for B61 was localized to a specific position on mouse chromosome 3 by interspecific back-cross analysis. ..
  31. Shiels A, Bennett T, Knopf H, Maraini G, Li A, Jiao X, et al. The EPHA2 gene is associated with cataracts linked to chromosome 1p. Mol Vis. 2008;14:2042-55 pubmed
    ..01 for cortical and/or nuclear cataracts). These data provide the first evidence that EPHA2, which functions in the Eph-ephrin bidirectional signaling pathway of mammalian cells, plays a vital role in maintaining lens transparency. ..
  32. Chang Q, Jorgensen C, Pawson T, Hedley D. Effects of dasatinib on EphA2 receptor tyrosine kinase activity and downstream signalling in pancreatic cancer. Br J Cancer. 2008;99:1074-82 pubmed publisher
    ..Using in vitro kinase assays, we found that EphA2 receptor tyrosine kinase was inhibited directly by dasatinib in a dose-dependent manner...
  33. Larsen A, Pedersen M, Stockhausen M, Grandal M, van Deurs B, Poulsen H. Activation of the EGFR gene target EphA2 inhibits epidermal growth factor-induced cancer cell motility. Mol Cancer Res. 2007;5:283-93 pubmed
    ..Ligand activation of EphA2 and EphA2 knockdown by small interfering RNA inhibit EGF-induced cell motility of EGFR-overexpressing human cancer cells, indicating a functional role of EphA2 in EGFR-expressing cancer cells. ..
  34. Mudali S, Fu B, Lakkur S, Luo M, Embuscado E, Iacobuzio Donahue C. Patterns of EphA2 protein expression in primary and metastatic pancreatic carcinoma and correlation with genetic status. Clin Exp Metastasis. 2006;23:357-65 pubmed
    ..Our data confirms that EphA2 is overexpressed in pancreatic cancer, but suggests a relative loss of EphA2 in co-existent pancreatic cancer metastases as well as a role for EPHA2 in organ specific metastasis. ..
  35. Walker Daniels J, Hess A, Hendrix M, Kinch M. Differential regulation of EphA2 in normal and malignant cells. Am J Pathol. 2003;162:1037-42 pubmed
  36. Koolpe M, Dail M, Pasquale E. An ephrin mimetic peptide that selectively targets the EphA2 receptor. J Biol Chem. 2002;277:46974-9 pubmed
    ..The EphA2 receptor is up-regulated in transformed cells and tumor vasculature where it likely contributes to cancer pathogenesis...
  37. Guo H, Miao H, Gerber L, Singh J, Denning M, Gilliam A, et al. Disruption of EphA2 receptor tyrosine kinase leads to increased susceptibility to carcinogenesis in mouse skin. Cancer Res. 2006;66:7050-8 pubmed
    b>EphA2 receptor tyrosine kinase is frequently overexpressed in different human cancers, suggesting that it may promote tumor development and progression...
  38. Brantley D, Cheng N, Thompson E, Lin Q, Brekken R, Thorpe P, et al. Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo. Oncogene. 2002;21:7011-26 pubmed
    ..Ephrin-A1 ligand was expressed in both tumor and endothelial cells, and EphA2 receptor was localized primarily in tumor-associated vascular endothelial cells...
  39. Pratt R, Kinch M. Activation of the EphA2 tyrosine kinase stimulates the MAP/ERK kinase signaling cascade. Oncogene. 2002;21:7690-9 pubmed
    ..Recent studies in our laboratory and others have demonstrated that the EphA2 receptor tyrosine kinase critically regulates tumor cell growth, migration and invasiveness...
  40. Miyazaki T, Kato H, Fukuchi M, Nakajima M, Kuwano H. EphA2 overexpression correlates with poor prognosis in esophageal squamous cell carcinoma. Int J Cancer. 2003;103:657-63 pubmed
    ..Consequently, patients with EphA2 overexpression have a poorer prognosis than those without. EphA2 is a potential target to prevent ESCC cells spreading into the lymphatic drainage. ..
  41. Brantley Sieders D, Caughron J, Hicks D, Pozzi A, Ruiz J, Chen J. EphA2 receptor tyrosine kinase regulates endothelial cell migration and vascular assembly through phosphoinositide 3-kinase-mediated Rac1 GTPase activation. J Cell Sci. 2004;117:2037-49 pubmed
    ..Moreover, EphA2-deficient endothelial cells fail to assemble in vivo when transplanted into recipient mice. These data suggest that EphA2 is an essential regulator of post-natal angiogenesis. ..
  42. Dobrzanski P, Hunter K, Jones Bolin S, Chang H, Robinson C, Pritchard S, et al. Antiangiogenic and antitumor efficacy of EphA2 receptor antagonist. Cancer Res. 2004;64:910-9 pubmed
    ..These data demonstrate a critical role of EphA signaling in tumor growth and metastasis and provide a strong rationale for targeting EphA2 receptors for anticancer therapies. ..
  43. Kinch M, Carles Kinch K. Overexpression and functional alterations of the EphA2 tyrosine kinase in cancer. Clin Exp Metastasis. 2003;20:59-68 pubmed
    ..In Recent studies have demonstrated that the EphA2 receptor tyrosine kinase is frequently overexpressed and functionally altered in aggressive tumor cells, and that these ..
  44. Ogawa K, Pasqualini R, Lindberg R, Kain R, Freeman A, Pasquale E. The ephrin-A1 ligand and its receptor, EphA2, are expressed during tumor neovascularization. Oncogene. 2000;19:6043-52 pubmed
    ..These data suggest that ephrin-A1 and EphA2 play a role in human cancers, at least in part by influencing tumor neovascularization. Eph proteins may represent promising new targets for antiangiogenic cancer treatments. ..
  45. Zeng G, Hu Z, Kinch M, Pan C, Flockhart D, Kao C, et al. High-level expression of EphA2 receptor tyrosine kinase in prostatic intraepithelial neoplasia. Am J Pathol. 2003;163:2271-6 pubmed
    ..Moreover, the presence of high levels of EphA2 in these cells suggests opportunities for prostate cancer prevention and treatment. ..
  46. Annamalai B, Liu X, Gopal U, Isaacs J. Hsp90 is an essential regulator of EphA2 receptor stability and signaling: implications for cancer cell migration and metastasis. Mol Cancer Res. 2009;7:1021-32 pubmed publisher
    ..the hypothesis that Hsp90 may regulate the activity of EphA2 and examined the potential relationship between EphA2 receptor signaling and chaperone function...
  47. Miao H, Wei B, Peehl D, Li Q, Alexandrou T, Schelling J, et al. Activation of EphA receptor tyrosine kinase inhibits the Ras/MAPK pathway. Nat Cell Biol. 2001;3:527-30 pubmed
    ..Our results identify EphA kinases as negative regulators of the Ras/MAPK pathway that exert anti-mitogenic functions in a cell-type-specific manner. ..
  48. Fang W, Brantley Sieders D, Parker M, Reith A, Chen J. A kinase-dependent role for EphA2 receptor in promoting tumor growth and metastasis. Oncogene. 2005;24:7859-68 pubmed
    ..One family member in particular, the EphA2 receptor, has been linked to breast, prostate, lung and colon cancer, as well as melanoma...
  49. Wykosky J, Gibo D, Debinski W. A novel, potent, and specific ephrinA1-based cytotoxin against EphA2 receptor expressing tumor cells. Mol Cancer Ther. 2007;6:3208-18 pubmed
    We have previously shown that the EphA2 receptor tyrosine kinase is overexpressed in glioblastoma multiforme (GBM) and represents a novel, attractive therapeutic target for the treatment of brain tumors...
  50. Zelinski D, Zantek N, Walker Daniels J, Peters M, Taparowsky E, Kinch M. Estrogen and Myc negatively regulate expression of the EphA2 tyrosine kinase. J Cell Biochem. 2002;85:714-20 pubmed
    ..These data reveal EphA2 as a downstream target of estrogen and Myc and suggest a mechanism by which estrogen and Myc may regulate breast cancer. ..
  51. Xu F, Zhong W, Li J, Shanshen Z, Cui J, Nesland J, et al. Predictive value of EphA2 and EphrinA-1 expression in oesophageal squamous cell carcinoma. Anticancer Res. 2005;25:2943-50 pubmed
    ..We conclude that EphA2 protein expression is confirmed to be of predictive value for unfavourable survival for oesophageal cancer patients and may be a good target for oesophageal cancer therapy. ..
  52. Zhang G, Njauw C, Park J, Naruse C, Asano M, Tsao H. EphA2 is an essential mediator of UV radiation-induced apoptosis. Cancer Res. 2008;68:1691-6 pubmed publisher
    ..These functional findings suggest that EphA2 is in fact an essential p53-independent, caspase-8-dependent proapoptotic factor induced by UVR. ..
  53. Kaul H, Riazuddin S, Shahid M, Kousar S, Butt N, Zafar A, et al. Autosomal recessive congenital cataract linked to EPHA2 in a consanguineous Pakistani family. Mol Vis. 2010;16:511-7 pubmed
    ..2353G>A, which results in an alanine to threonine substitution (p.A785T). Here, we report for the first time a missense mutation in EPHA2 associated with autosomal recessive congenital cataracts. ..