8j1i

Structural highlights

Function

EPHA8_MOUSE Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. The GPI-anchored ephrin-A EFNA2, EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation. With EFNA5 may regulate integrin-mediated cell adhesion and migration on fibronectin substrate but also neurite outgrowth. During development of the nervous system also plays a role in axon guidance. Downstream effectors of the EPHA8 signaling pathway include FYN which promotes cell adhesion upon activation by EPHA8 and the MAP kinases in the stimulation of neurite outgrowth.^{[1] [2] [3] [4] [5] [6]}

References

1. ↑ Choi S, Park S. Phosphorylation at Tyr-838 in the kinase domain of EphA8 modulates Fyn binding to the Tyr-615 site by enhancing tyrosine kinase activity. Oncogene. 1999 Sep 23;18(39):5413-22. PMID:10498895 doi:10.1038/sj.onc.1202917
2. ↑ Gu C, Park S. The EphA8 receptor regulates integrin activity through p110gamma phosphatidylinositol-3 kinase in a tyrosine kinase activity-independent manner. Mol Cell Biol. 2001 Jul;21(14):4579-97. PMID:11416136 doi:10.1128/MCB.21.14.4579-4597.2001
3. ↑ Gu C, Park S. The p110 gamma PI-3 kinase is required for EphA8-stimulated cell migration. FEBS Lett. 2003 Apr 10;540(1-3):65-70. PMID:12681484 doi:10.1016/s0014-5793(03)00223-0
4. ↑ Gu C, Shim S, Shin J, Kim J, Park J, Han K, Park S. The EphA8 receptor induces sustained MAP kinase activation to promote neurite outgrowth in neuronal cells. Oncogene. 2005 Jun 16;24(26):4243-56. PMID:15782114 doi:10.1038/sj.onc.1208584
5. ↑ Shin J, Gu C, Park E, Park S. Identification of phosphotyrosine binding domain-containing proteins as novel downstream targets of the EphA8 signaling function. Mol Cell Biol. 2007 Dec;27(23):8113-26. Epub 2007 Sep 17. PMID:17875921 doi:http://dx.doi.org/MCB.00794-07
6. ↑ Park S, Frisén J, Barbacid M. Aberrant axonal projections in mice lacking EphA8 (Eek) tyrosine protein kinase receptors. EMBO J. 1997 Jun 2;16(11):3106-14. PMID:9214628 doi:10.1093/emboj/16.11.3106