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PMID:15782114

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Citation

Gu, C, Shim, S, Shin, J, Kim, J, Park, J, Han, K and Park, S (2005) The EphA8 receptor induces sustained MAP kinase activation to promote neurite outgrowth in neuronal cells. Oncogene 24:4243-56

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.

Links

PubMed Online version:10.1038/sj.onc.1208584

Keywords

Animals; Brain Neoplasms/genetics; Brain Neoplasms/pathology; Brain Neoplasms/veterinary; Enzyme Activation; Glioma/genetics; Glioma/pathology; Glioma/veterinary; Mice; Mitogen-Activated Protein Kinases/biosynthesis; Mitogen-Activated Protein Kinases/genetics; Mitogen-Activated Protein Kinases/pharmacology; Neurites; Neuroblastoma/genetics; Neuroblastoma/pathology; Neuroblastoma/veterinary; Neurons; Protein-Tyrosine Kinases/genetics; Rats; Receptor, EphA8/genetics; Receptor, EphA8/physiology; Signal Transduction; Tumor Cells, Cultured

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:EPHA8

involved_in

GO:0031175: neuron projection development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:EPHA8

involved_in

GO:0043410: positive regulation of MAPK cascade

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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