Regulating angiogenesis at the level of PtdIns-4,5-P2.
Angiogenesis is a coordinated sequence of cellular responses that result in the outgrowth of new blood vessels. The angiogenic program is regulated by extracellular factors, whose input is integrated at least in part at the level of signal transduction pathways driven by phosphoinositide 3 kinase (PI3K) and phospholipase Cgamma (PLCgamma). Using an in vitro angiogenesis model, we discovered that PI3K was essential for tube formation, whereas PLCgamma promoted regression. The underlying mechanism by which PLCgamma antagonized tube formation appeared to be by competing with PI3K for their common substrate, phosphatidylinositol-4,5-bisphosphate. These studies are the first to identify signaling enzymes involved with vessel regression, and reveal that the angiogenic program can be coordinated by the availability of a membrane lipid.
Im
Eunok
E
Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USA.
Kazlauskas
Andrius
A
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004789:Enzyme Activation; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051966:Phospholipase C gamma / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D008563:Membrane Lipids; D019869:Phosphatidylinositol 3-Kinases; D019269:Phosphatidylinositol 4,5-Diphosphate; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051966:Phospholipase C gamma; D051057:Proto-Oncogene Proteins c-akt; D017479:Receptors, Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A