Src family kinases promote vessel stability by antagonizing the Rho/ROCK pathway.
Src family kinases (SFKs) are one of the signaling enzymes that contribute to angiogenesis, but their precise input to the various phases of the angiogenic program has not been defined. Using an in vitro model system, we discovered that SFKs promoted the formation of tubes and prevented their regression. They suppressed regression by activating the ERK pathway that antagonized the Rho/ROCK pathway, which was essential for regression. These studies reveal that SFKs contribute to several phases of the angiogenic program and identify the downstream effectors by which SFKs stabilize tubes.
Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts 02114, USA.
Eunok
E
Im
Andrius
A
Kazlauskas
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D009389:Neovascularization, Pathologic; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054460:rho-Associated Kinases; D019061:src-Family Kinases / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D019061:src-Family Kinases; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020741:rho GTP-Binding Proteins