Letter abstract
Nature Cell Biology 10, 329 - 337 (2008)
Published online: 10 February 2008 | doi:10.1038/ncb1695
Regulation of VEGF-mediated angiogenesis by the Akt/PKB substrate Girdin
Tomoya Kitamura1,8, Naoya Asai2,8, Atsushi Enomoto2,4,8, Kengo Maeda1, Takuya Kato2, Maki Ishida2, Ping Jiang2, Takashi Watanabe3,4, Jiro Usukura5, Takahisa Kondo1, Frank Costantini6, Toyoaki Murohara1 & Masahide Takahashi2,7
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.
- Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
- Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
- Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
- Institute for Advanced Research, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
- Division of Associated Research Projects, EcoTopia Science Institute, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
- Department of Genetics and Development, Columbia University, 701 West 168th Street, New York, NY 10032, USA.
- Division of Molecular Pathology, Center for Neurological Disease and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
- These authors equally contributed to this work.
Correspondence to: Masahide Takahashi2,7 e-mail: mtakaha@med.nagoya-u.ac.jp
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