Аннотация:This study provides evidence that expression of EphA8 receptor in NG108–15 cells results in a substantial increase in the number of neurite‐bearing cells. However, the EphA8‐induced neurite outgrowth does not require either ephrin‐A5 stimulation or ectopic expression of p110γPI‐3 kinase. In contrast, co‐expression of a lipid kinase‐inactive p110γ mutant together with EphA8 causes neurite retraction in the presence of ephrin‐A5 stimulation. This effect was not observed in the absence of ephrin‐A5 stimulation. Significantly, the tyrosine kinase activity of EphA8 is not important for either of these processes. Taken together, our results strongly suggest that p110γ PI‐3 kinase is critically involved in the regulatory process by which ephrin‐A5 exerts effects on the EphA8‐induced neurite outgrowth.