The p110 gamma PI-3 kinase is required for EphA8-stimulated cell migration.
This study provides evidence that treatment with preclustered ephrin A5-Fc results in a substantial increase in the stability of the p110 gamma PI-3 kinase associated with EphA8, thereby enhancing PI-3 kinase activity and cell migration on a fibronectin substrate. In contrast, co-expression of a lipid kinase-inactive p110 gamma mutant together with EphA8 inhibits ligand-stimulated PI-3 kinase activity and cell migration on a fibronectin substrate, suggesting that the mutant has a dominant negative effect against the endogenous p110 gamma PI-3 kinase. Significantly, the tyrosine kinase activity of EphA8 is not important for either of these processes. Taken together, our results demonstrate that the stimulation of cell migration on a fibronectin substrate by the EphA8 receptor depends on the p110 gamma PI-3 kinase but is independent of a tyrosine kinase activity.
Gu
Changkyu
C
Institute of Natural Science, Sookmyung Women's University, 53-12 Chungpa-Dong 2-Ka, Yongsan-Ku, Seoul 140-742, South Korea.
Park
Soochul
S
D000595:Amino Acid Sequence; D015153:Blotting, Western; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011233:Precipitin Tests; D036143:Receptor, EphA8 / Q000502:physiology*
D019869:Phosphatidylinositol 3-Kinases; D036143:Receptor, EphA8