Regulating angiogenesis at the level of PtdIns-4,5-P2
- 20 April 2006
- journal article
- Published by Springer Nature in The EMBO Journal
- Vol. 25 (10) , 2075-2082
- https://doi.org/10.1038/sj.emboj.7601100
Abstract
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.Keywords
This publication has 26 references indexed in Scilit:
- The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesisGenes & Development, 2005
- Cathepsin B Regulates the Intrinsic Angiogenic Threshold of Endothelial CellsMolecular Biology of the Cell, 2005
- MMP-1 activation by serine proteases and MMP-10 induces human capillary tubular network collapse and regression in 3D collagen matricesJournal of Cell Science, 2005
- Microtubule Depolymerization Rapidly Collapses Capillary Tube Networks in Vitro and Angiogenic Vessels in Vivo through the Small GTPase RhoJournal of Biological Chemistry, 2004
- RhoB controls Akt trafficking and stage-specific survival of endothelial cells during vascular developmentGenes & Development, 2003
- A new link between the c-Abl tyrosine kinase and phosphoinositide signalling through PLC-γ1Nature Cell Biology, 2003
- Absence of Erythrogenesis and Vasculogenesis in Plcg1-deficient MiceJournal of Biological Chemistry, 2002
- Vascular Endothelial Growth Factor Regulates Endothelial Cell Survival through the Phosphatidylinositol 3′-Kinase/Akt Signal Transduction PathwayJournal of Biological Chemistry, 1998
- Phospholipase C-γ1 and phosphatidylinositol 3 kinase are the downstream mediators of the PDGF receptor's mitogenic signalCell, 1993
- Culture of retinal capillary cells using selective growth mediaMicrovascular Research, 1983