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Prepublished online as a Blood First Edition Paper on June 19, 2003; DOI 10.1182/blood-2003-03-0670.

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2003-03-0670v1
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Submitted March 3, 2003
Accepted June 4, 2003

Tie-2 - dependent activation of RhoA and Rac1 participates in endothelial cell motility triggered by angiopoietin-1

Ilaria Cascone, Enrica Audero, Enrico Giraudo, Lucia Napione, Fabrizio Maniero, Mark R Philips, John G Collard, Guido Serini, and Federico Bussolino*

Department of Oncological Sciences, University of Torino, Candiolo, Torino, Italy; Divisiono of Molecular Angiogenesis, Institute for Cancer Research and Treatment, Candiolo, Torino, Italy
Departments of Medicine, Cell Biology and Pharmacology, New York University School Medicine, New York, NY, USA
Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

* Corresponding author; email: federico.bussolino{at}ircc.it.

Angiopoietin-1 is implicated in the maturation and remodeling of vascular network during embryo development and in adult life. Through its tyrosine kinase receptor Tie-2 it stimulates endothelial cells to migrate and change shape. Here we show that angiopoietin-1 elicits chemokinesis of endothelial cells by a phosphoinositide 3-OH kinase / Son of sevenless-dependent modulation of Rac1 and RhoA. The resulting temporal events are associated with cytoskeletal rearrangements and occur in discrete zones of the cell. Endothelial cells carrying dominant negative mutants of RhoA and Rac1 or treated with LY294002, an inhibitor of phosphoinositide 3-OH kinase, drammaticaly decrease their chemokinetic velocity. Taken together, these results further expand our understanding of angiopoietin-1-mediated endothelial cell motility during vascular network assembly and angiogenesis.


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