PI(4,5)P₂-dependent regulation of endothelial tip cell specification contributes to angiogenesis.

ABSTRACT: 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)P₂ to PI(3,4,5)P₃, activating AKT; however, PI3K/AKT does not direct tip cell specification. We report that PI(4,5)P₂ hydrolysis by the phosphoinositide-5-phosphatase, INPP5K, contributes to angiogenesis. INPP5K ablation disrupted tip cell specification and impaired embryonic angiogenesis associated with enhanced DLL4/NOTCH signaling. INPP5K degraded a pool of PI(4,5)P₂ generated by PIP5K1C phosphorylation of PI(4)P in endothelial cells. INPP5K ablation increased PI(4,5)P₂, thereby releasing β-catenin from the plasma membrane, and concurrently inc

SUBMITTER: Davies EM 

PROVIDER: S-EPMC10065449 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature