title: The EphA8 receptor induces sustained MAP kinase activation to promote neurite outgrowth in neuronal cells.
abstract: Recent studies in our laboratory demonstrate that ligand-mediated activation of the EphA8 receptor critically regulates cell adhesion and migration. In this report, we show that the EphA8 receptor induces neurite outgrowth in NG108-15 cells in the absence of ligand stimulation. Using various deletion mutants lacking specific intracytoplasmic regions, we confirm that the tyrosine kinase domain of EphA8 is important for inducing neurite outgrowth. However, the tyrosine kinase activity of EphA8 is not crucial for neurite outgrowth induction. Treatment with various inhibitors further reveals that the mitogen-activated protein kinase (MAPK) signaling pathway is critical for neurite outgrowth induced by EphA8. Consistent with these results, EphA8 expression induced a sustained increase in the activity of MAPK, whereas ligand-mediated EphA8 activation had no further modulatory effects on MAP kinase activity. Additionally, activated MAPK relocalized from the cytoplasm to the nucleus in response to EphA8 transfection. These results collectively suggest that the EphA8 receptor is capable of inducing a sustained increase in MAPK activity, thereby promoting neurite outgrowth in neuronal cells.
authors.affiliation: Institute of Natural Science, Sookmyung Women's University, 53-12 Chungpa-Dong 2-Ka, Yongsan-Ku, Seoul 140-742, Korea.
authors.forename: Changkyu
authors.initials: C
authors.lastname: Gu
authors.forename: Sungbo
authors.initials: S
authors.lastname: Shim
authors.forename: Jongdae
authors.initials: J
authors.lastname: Shin
authors.forename: Jieun
authors.initials: J
authors.lastname: Kim
authors.forename: Jonghoon
authors.initials: J
authors.lastname: Park
authors.forename: Kyuhyung
authors.initials: K
authors.lastname: Han
authors.forename: Soochul
authors.initials: S
authors.lastname: Park
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000662:veterinary; D004789:Enzyme Activation; D005910:Glioma / Q000235:genetics / Q000473:pathology / Q000662:veterinary; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*; D016501:Neurites; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology / Q000662:veterinary; D009474:Neurons; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D051381:Rats; D036143:Receptor, EphA8 / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D011505:Protein-Tyrosine Kinases; D036143:Receptor, EphA8; D020928:Mitogen-Activated Protein Kinases