| First Author | Lee NY | Year | 2012 |
| Journal | Mol Biol Cell | Volume | 23 |
| Issue | 13 | Pages | 2412-23 |
| PubMed ID | 22593212 | Mgi Jnum | J:198766 |
| Mgi Id | MGI:5499091 | Doi | 10.1091/mbc.E11-12-0993 |
| Citation | Lee NY, et al. (2012) Endoglin regulates PI3-kinase/Akt trafficking and signaling to alter endothelial capillary stability during angiogenesis. Mol Biol Cell 23(13):2412-23 |
| abstractText | Endoglin (CD105) is an endothelial-specific transforming growth factor beta (TGF-beta) coreceptor essential for angiogenesis and vascular homeostasis. Although endoglin dysfunction contributes to numerous vascular conditions, the mechanism of endoglin action remains poorly understood. Here we report a novel mechanism in which endoglin and Galpha-interacting protein C-terminus-interacting protein (GIPC)-mediated trafficking of phosphatidylinositol 3-kinase (PI3K) regulates endothelial signaling and function. We demonstrate that endoglin interacts with the PI3K subunits p110alpha and p85 via GIPC to recruit and activate PI3K and Akt at the cell membrane. Opposing ligand-induced effects are observed in which TGF-beta1 attenuates, whereas bone morphogenetic protein-9 enhances, endoglin/GIPC-mediated membrane scaffolding of PI3K and Akt to alter endothelial capillary tube stability in vitro. Moreover, we employ the first transgenic zebrafish model for endoglin to demonstrate that GIPC is a critical component of endoglin function during developmental angiogenesis in vivo. These studies define a novel non-Smad function for endoglin and GIPC in regulating endothelial cell function during angiogenesis. |
