Regulation of VEGF-mediated angiogenesis by the Akt/PKB substrate Girdin.

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 Biol

journal_title

Nature cell biology

authors

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 M

doi

10.1038/ncb1695

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

329-37

issue

3

eissn

1465-7392

issn

1476-4679

pii

ncb1695

journal_volume

10

pub_type

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