Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Actins / metabolism
-
Angiogenesis Inducing Agents / pharmacology*
-
Angiopoietin-1
-
Animals
-
COS Cells
-
Cell Compartmentation / physiology
-
Cell Movement / drug effects
-
Cell Movement / physiology*
-
Chemotaxis / drug effects
-
Chemotaxis / physiology
-
Cytoskeleton / metabolism
-
Endothelium, Vascular / cytology
-
Endothelium, Vascular / metabolism*
-
Humans
-
Membrane Glycoproteins / pharmacology*
-
Phosphatidylinositol 3-Kinases / metabolism
-
Receptor Protein-Tyrosine Kinases / metabolism*
-
Receptor, TIE-2
-
SOS1 Protein / metabolism
-
Signal Transduction / drug effects
-
Signal Transduction / physiology
-
Veins / cytology
-
rac1 GTP-Binding Protein / genetics
-
rac1 GTP-Binding Protein / metabolism*
-
rhoA GTP-Binding Protein / genetics
-
rhoA GTP-Binding Protein / metabolism*
Substances
-
Actins
-
Angiogenesis Inducing Agents
-
Angiopoietin-1
-
Membrane Glycoproteins
-
SOS1 Protein
-
Phosphatidylinositol 3-Kinases
-
Receptor Protein-Tyrosine Kinases
-
Receptor, TIE-2
-
rac1 GTP-Binding Protein
-
rhoA GTP-Binding Protein