Coordinated functions of Akt/PKB and ETS1 in tubule formation.

We investigated the inter-relationship between two downstream effectors of vascular endothelial growth factor (VEGF), the serine threonine kinase Akt (also known as protein kinase B) and the transcription factor ETS1, during tubulogenesis. Human endothelial cell culture and the in vivo Drosophila tracheal systems are employed in comparative analysis. We show that VEGF stimulates the expression of ETS1 through a phosphatidylinositol-3-kinase (PI3K)/Akt-dependent pathway in primary endothelial cells. Activation of Akt results in vessel formation in vitro, a process that is blocked by expression of antisense ETS1. The functional relationship between ETS and Akt was then tested in the homologous tubular system in Drosophila. Contrary to expectation, ETS1 and Akt did not form a linear positive regulatory pathway in vivo. Instead, genetic analyses suggest that the Drosophila ETS1 homologue Pointed is required for cell motility per se while Drosophila Akt (Dakt1) is responsible for organized and restricted cell movement that is essential for tubule formation. Taken together, our results show that ETS1 and Akt control different aspects of cell motility that are integrated in the precise regulation of vascular tubule formation.