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

Research output: Contribution to journalArticlepeer-review

199 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)329-337
Number of pages9
JournalNature Cell Biology
Issue number3
Publication statusPublished - 03-2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology


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