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词条 EPH receptor A2
释义

  1. Function

  2. Clinical significance

  3. Interactions

  4. References

  5. Further reading

{{Infobox_gene}}EPH receptor A2 (ephrin type-A receptor 2) is a protein that in humans is encoded by the EPHA2 gene.[1][2]

Function

This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into two groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. This gene encodes a protein that binds ephrin-A ligands.[2]

Clinical significance

It may be implicated in BRAF mutated melanomas becoming resistant to BRAF-inhibitors and MEK inhibitors.[3] It is also the receptor by which Kaposi sarcoma-associated herpesvirus (KSHV) enters host cells; small molecule inhibitors of EphA2 have shown some ability to block KSHV entry into human cells.[4]

Interactions

EPH receptor A2 has been shown to interact with:

  • ACP1[5]
  • Grb2,[6]
  • PIK3R1,[7] and
  • SHC1.[6]

References

1. ^{{cite journal | vauthors = Sulman EP, Tang XX, Allen C, Biegel JA, Pleasure DE, Brodeur GM, Ikegaki N | title = ECK, a human EPH-related gene, maps to 1p36.1, a common region of alteration in human cancers | journal = Genomics | volume = 40 | issue = 2 | pages = 371–4 | date = April 1997 | pmid = 9119409 | pmc = | doi = 10.1006/geno.1996.4569 }}
2. ^1 {{cite web | title = Entrez Gene: EPHA2 EPH receptor A2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1969| accessdate = }}
3. ^{{cite web |url=http://www.oncotherapynetwork.com/skin-cancer-melanoma-targets/counteracting-drug-resistance-melanoma |title=Counteracting Drug Resistance in Melanoma |year=2015 }}
4. ^{{cite journal | vauthors = Hahn AS, Kaufmann JK, Wies E, Naschberger E, Panteleev-Ivlev J, Schmidt K, Holzer A, Schmidt M, Chen J, König S, Ensser A, Myoung J, Brockmeyer NH, Stürzl M, Fleckenstein B, Neipel F | title = The ephrin receptor tyrosine kinase A2 is a cellular receptor for Kaposi's sarcoma–associated herpesvirus | journal = Nat. Med. | volume = 18 | issue = 6 | pages = 961–6 | year = 2012 | pmid = 22635007 | pmc = 3645317 | doi = 10.1038/nm.2805 }}
5. ^{{cite journal | vauthors = Kikawa KD, Vidale DR, Van Etten RL, Kinch MS | title = Regulation of the EphA2 kinase by the low molecular weight tyrosine phosphatase induces transformation | journal = J. Biol. Chem. | volume = 277 | issue = 42 | pages = 39274–9 | date = October 2002 | pmid = 12167657 | doi = 10.1074/jbc.M207127200 }}
6. ^1 {{cite journal | vauthors = Pratt RL, Kinch MS | title = Activation of the EphA2 tyrosine kinase stimulates the MAP/ERK kinase signaling cascade | journal = Oncogene | volume = 21 | issue = 50 | pages = 7690–9 | date = October 2002 | pmid = 12400011 | doi = 10.1038/sj.onc.1205758 }}
7. ^{{cite journal | vauthors = Pandey A, Lazar DF, Saltiel AR, Dixit VM | title = Activation of the Eck receptor protein tyrosine kinase stimulates phosphatidylinositol 3-kinase activity | journal = J. Biol. Chem. | volume = 269 | issue = 48 | pages = 30154–7 | date = December 1994 | pmid = 7982920 | doi = }}

Further reading

{{refbegin | 2}}
  • {{cite journal | vauthors = Flanagan JG, Vanderhaeghen P | title = The ephrins and Eph receptors in neural development | journal = Annu. Rev. Neurosci. | volume = 21 | issue = | pages = 309–45 | year = 1998 | pmid = 9530499 | doi = 10.1146/annurev.neuro.21.1.309 }}
  • {{cite journal | vauthors = Zhou R | title = The Eph family receptors and ligands | journal = Pharmacol. Ther. | volume = 77 | issue = 3 | pages = 151–81 | year = 1998 | pmid = 9576626 | doi = 10.1016/S0163-7258(97)00112-5 }}
  • {{cite journal | vauthors = Holder N, Klein R | title = Eph receptors and ephrins: effectors of morphogenesis | journal = Development | volume = 126 | issue = 10 | pages = 2033–44 | year = 1999 | pmid = 10207129 | doi = }}
  • {{cite journal | vauthors = Wilkinson DG | title = Eph receptors and ephrins: regulators of guidance and assembly | journal = Int. Rev. Cytol. | volume = 196 | issue = | pages = 177–244 | year = 2000 | pmid = 10730216 | doi = 10.1016/S0074-7696(00)96005-4 }}
  • {{cite journal | vauthors = Xu Q, Mellitzer G, Wilkinson DG | title = Roles of Eph receptors and ephrins in segmental patterning | journal = Philos. Trans. R. Soc. Lond. B Biol. Sci. | volume = 355 | issue = 1399 | pages = 993–1002 | year = 2000 | pmid = 11128993 | pmc = 1692797 | doi = 10.1098/rstb.2000.0635 }}
  • {{cite journal | vauthors = Wilkinson DG | title = Multiple roles of EPH receptors and ephrins in neural development | journal = Nat. Rev. Neurosci. | volume = 2 | issue = 3 | pages = 155–64 | year = 2001 | pmid = 11256076 | doi = 10.1038/35058515 }}
  • {{cite journal | vauthors = Kinch MS, Carles-Kinch K | title = Overexpression and functional alterations of the EphA2 tyrosine kinase in cancer | journal = Clin. Exp. Metastasis | volume = 20 | issue = 1 | pages = 59–68 | year = 2003 | pmid = 12650608 | doi = 10.1023/A:1022546620495 }}
  • {{cite journal | vauthors = Walker-Daniels J, Hess AR, Hendrix MJ, Kinch MS | title = Differential regulation of EphA2 in normal and malignant cells | journal = Am. J. Pathol. | volume = 162 | issue = 4 | pages = 1037–42 | year = 2003 | pmid = 12651595 | pmc = 1851246 | doi = 10.1016/S0002-9440(10)63899-0 }}
  • {{cite journal | vauthors = Lindberg RA, Hunter T | title = cDNA cloning and characterization of eck, an epithelial cell receptor protein-tyrosine kinase in the eph/elk family of protein kinases | journal = Mol. Cell. Biol. | volume = 10 | issue = 12 | pages = 6316–24 | year = 1990 | pmid = 2174105 | pmc = 362907 | doi = }}
  • {{cite journal | vauthors = Pandey A, Shao H, Marks RM, Polverini PJ, Dixit VM | title = Role of B61, the ligand for the Eck receptor tyrosine kinase, in TNF-alpha-induced angiogenesis | journal = Science | volume = 268 | issue = 5210 | pages = 567–9 | year = 1995 | pmid = 7536959 | doi = 10.1126/science.7536959 }}
  • {{cite journal | vauthors = Pandey A, Duan H, Dixit VM | title = Characterization of a novel Src-like adapter protein that associates with the Eck receptor tyrosine kinase | journal = J. Biol. Chem. | volume = 270 | issue = 33 | pages = 19201–4 | year = 1995 | pmid = 7543898 | doi = 10.1074/jbc.270.33.19201 }}
  • {{cite journal | vauthors = Ruiz JC, Robertson EJ | title = The expression of the receptor-protein tyrosine kinase gene, eck, is highly restricted during early mouse development | journal = Mech. Dev. | volume = 46 | issue = 2 | pages = 87–100 | year = 1994 | pmid = 7918100 | doi = 10.1016/0925-4773(94)90078-7 }}
  • {{cite journal | vauthors = Davis S, Gale NW, Aldrich TH, Maisonpierre PC, Lhotak V, Pawson T, Goldfarb M, Yancopoulos GD | title = Ligands for EPH-related receptor tyrosine kinases that require membrane attachment or clustering for activity | journal = Science | volume = 266 | issue = 5186 | pages = 816–9 | year = 1994 | pmid = 7973638 | doi = 10.1126/science.7973638 }}
  • {{cite journal | vauthors = Pandey A, Lazar DF, Saltiel AR, Dixit VM | title = Activation of the Eck receptor protein tyrosine kinase stimulates phosphatidylinositol 3-kinase activity | journal = J. Biol. Chem. | volume = 269 | issue = 48 | pages = 30154–7 | year = 1994 | pmid = 7982920 | doi = }}
  • {{cite journal | vauthors = Ganju P, Shigemoto K, Brennan J, Entwistle A, Reith AD | title = The Eck receptor tyrosine kinase is implicated in pattern formation during gastrulation, hindbrain segmentation and limb development | journal = Oncogene | volume = 9 | issue = 6 | pages = 1613–24 | year = 1994 | pmid = 8183555 | doi = }}
  • {{cite journal | vauthors = 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 | title = Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis | journal = Neuron | volume = 17 | issue = 1 | pages = 9–19 | year = 1996 | pmid = 8755474 | doi = 10.1016/S0896-6273(00)80276-7 }}
  • {{cite journal | vauthors = Kozlosky CJ, VandenBos T, Park L, Cerretti DP, Carpenter MK | title = LERK-7: a ligand of the Eph-related kinases is developmentally regulated in the brain | journal = Cytokine | volume = 9 | issue = 8 | pages = 540–9 | year = 1997 | pmid = 9245480 | doi = 10.1006/cyto.1997.0199 }}
  • {{cite journal | vauthors = Ephnomenclaturecommittee, | title = Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph Nomenclature Committee | journal = Cell | volume = 90 | issue = 3 | pages = 403–4 | year = 1997 | pmid = 9267020 | doi = 10.1016/S0092-8674(00)80500-0 }}
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