Tie-2-dependent activation of RhoA and Rac1 participates in endothelial cell motility triggered by angiopoietin-1.
Angiopoietin-1 is implicated in the maturation and remodeling of the 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, dramatically 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.
Cascone
Ilaria
I
Department of Oncological Sciences, University of Torino, Candiolo, Italy.
Audero
Enrica
E
Giraudo
Enrico
E
Napione
Lucia
L
Maniero
Fabrizio
F
Philips
Mark R
MR
Collard
John G
JG
Serini
Guido
G
Bussolino
Federico
F
D000199:Actins / Q000378:metabolism; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D042683:Angiopoietin-1; D000818:Animals; D019556:COS Cells; D002451:Cell Compartmentation / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D042787:Receptor, TIE-2; D020837:SOS1 Protein / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014680:Veins / Q000166:cytology; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; D008562:Membrane Glycoproteins; D020837:SOS1 Protein; D019869:Phosphatidylinositol 3-Kinases; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein