Article
- The EMBO Journal (2006) 25, 2075 - 2082
- doi:10.1038/sj.emboj.7601100
Published online: 20 April 2006
Subject Category:
Regulating angiogenesis at the level of PtdIns-4,5-P2
Eunok Im and Andrius Kazlauskas
- Schepens Eye Research Institute, Harvard Medical School, Boston, MA, USA
Correspondence to:
Andrius Kazlauskas, Schepens Eye Research Institute, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA. Tel.: +1 617 912 2517; Fax: +1 617 912 0111; E-mail: ak@eri.harvard.edu
Received 21 November 2005; Accepted 27 March 2006
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 C
(PLC). Using an in vitro angiogenesis model, we discovered that PI3K was essential for tube formation, whereas PLC promoted regression. The underlying mechanism by which PLC 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:
- angiogenesis,
- PI3K,
- PLC,
- PtdIns-4,5-P2,
- tube regression
