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.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Kitamura T,Asai N,Enomoto A,Maeda K,Kato T,Ishida M,Jiang P,Watanabe T,Usukura J,Kondo T,Costantini F,Murohara T,Takahashi Mdoi
10.1038/ncb1695subject
Has Abstractpub_date
2008-03-01 00:00:00pages
329-37issue
3eissn
1465-7392issn
1476-4679pii
ncb1695journal_volume
10pub_type
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