{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["9(13)"],"submitter":["Davies EM"],"pubmed_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)P<sub>2</sub> to PI(3,4,5)P<sub>3</sub>, activating AKT; however, PI3K/AKT does not direct tip cell specification. We report that PI(4,5)P<sub>2</sub> 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)P<sub>2</sub> generated by PIP5K1C phosphorylation of PI(4)P in endothelial cells. INPP5K ablation increased PI(4,5)P<sub>2</sub>, thereby releasing β-catenin from the plasma membrane, and concurrently inc"],"journal":["Science advances"],"pagination":["eadd6911"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10065449"],"repository":["biostudies-literature"],"pubmed_title":["PI(4,5)P<sub>2</sub>-dependent regulation of endothelial tip cell specification contributes to angiogenesis."],"pmcid":["PMC10065449"],"pubmed_authors":["Le KQ","Roan KTT","Schwarz Q","Mitchell CA","Davies EM","Gurung R","Harvey RP","Mitchell GM"],"additional_accession":[]},"is_claimable":false,"name":"PI(4,5)P<sub>2</sub>-dependent regulation of endothelial tip cell specification contributes to angiogenesis.","description":"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<sub>2</sub> to PI(3,4,5)P<sub>3</sub>, activating AKT; however, PI3K/AKT does not direct tip cell specification. We report that PI(4,5)P<sub>2</sub> 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)P<sub>2</sub> generated by PIP5K1C phosphorylation of PI(4)P in endothelial cells. INPP5K ablation increased PI(4,5)P<sub>2</sub>, thereby releasing β-catenin from the plasma membrane, and concurrently inc","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Mar","modification":"2025-04-04T21:09:39.655Z","creation":"2025-04-04T21:09:39.655Z"},"accession":"S-EPMC10065449","cross_references":{"pubmed":["37000875"],"doi":["10.1126/sciadv.add6911"]}}