PI(4,5)P-dependent regulation of endothelial tip cell specification contributes to angiogenesis.

Dynamic positioning of endothelial tip and stalk cells, via the interplay between VEGFR2 and NOTCH signaling, is essential for angiogenesis. VEGFR2 activates PI3K, which phosphorylates PI(4,5)P to PI(3,4,5)P, activating AKT; however, PI3K/AKT does not direct tip cell specification. We report that PI(4,5)P hydrolysis by the phosphoinositide-5-phosphatase, INPP5K, contributes to angiogenesis.