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

Tomoya Kitamura, Naoya Asai, Atsushi Enomoto, Kengo Maeda, Takuya Kato, Maki Ishida, Ping Jiang, Takashi Watanabe, Jiro Usukura, Takahisa Kondo, Frank Costantini, Toyoaki Murohara, Masahide Takahashi

研究成果: Article査読

181 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)329-337
ページ数9
ジャーナルNature Cell Biology
10
3
DOI
出版ステータスPublished - 03-2008
外部発表はい

All Science Journal Classification (ASJC) codes

  • Cell Biology

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