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Regulation of VEGF-mediated angiogenesis by the Akt/PKB substrate Girdin.
- Source :
-
Nature cell biology [Nat Cell Biol] 2008 Mar; Vol. 10 (3), pp. 329-37. Date of Electronic Publication: 2008 Feb 10. - Publication Year :
- 2008
-
Abstract
- The serine/threonine protein kinase Akt is involved in a variety of cellular processes including cell proliferation, survival, metabolism and gene expression. It is essential in vascular endothelial growth factor (VEGF)-mediated angiogenesis; however, it is not known how Akt regulates the migration of endothelial cells, a crucial process for vessel sprouting, branching and the formation of networks during angiogenesis. Here we report that Akt-mediated phosphorylation of Girdin, an actin-binding protein, promotes VEGF-dependent migration of endothelial cells and tube formation by these cells. We found that exogenously delivered adenovirus harbouring Girdin short interfering RNA in Matrigel embedded in mice, markedly inhibited VEGF-mediated angiogenesis. Targeted disruption of the Girdin gene in mice impaired vessel remodelling in the retina and angiogenesis from aortic rings, whereas Girdin was dispensable for embryonic vasculogenesis. These findings demonstrate that the Akt/Girdin signalling pathway is essential in VEGF-mediated postneonatal angiogenesis.
- Subjects :
- Animals
Aorta metabolism
Cell Movement
Endothelial Cells metabolism
Humans
Mice
Mice, Transgenic
Models, Biological
RNA, Small Interfering metabolism
Microfilament Proteins metabolism
Neovascularization, Pathologic
Proto-Oncogene Proteins c-akt metabolism
Vascular Endothelial Growth Factor A metabolism
Vesicular Transport Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4679
- Volume :
- 10
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Nature cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 18264090
- Full Text :
- https://doi.org/10.1038/ncb1695