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VEGF treatment induces signaling pathways that regulate both actin polymerization and depolymerization
Chunhong Gong1, Konstantin V Stoletov, Bruce I Terman
1Cardiology Division, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
Angiogenesis
|May 12, 2005
Summary
Vascular endothelial growth factor (VEGF) drives cell migration by reorganizing actin. This study reveals VEGF controls actin polymerization via N-WASP and Nck, and depolymerization through cofilin and LIM-kinase, regulated by PI3-K and ROCK.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Vascular endothelial growth factor (VEGF) is crucial for angiogenesis and endothelial cell migration.
- Actin cytoskeleton reorganization is vital for cell migration but the underlying signaling pathways for VEGF-induced changes are not fully understood.
- VEGF influences multiple signaling pathways to regulate cell behavior.
Purpose of the Study:
- To elucidate the signaling pathways mediating actin reorganization in response to VEGF.
- To investigate the roles of N-WASP, Nck, cofilin, LIM-kinase, PAK, PI3-K, and ROCK in VEGF-induced actin dynamics.
- To understand the mechanisms of actin polymerization and depolymerization during VEGF-stimulated endothelial cell migration.
Main Methods:
- Dominant-negative protein expression to block specific signaling molecules.
- Cellular redistribution assays to track protein localization.
- Western blotting to detect protein phosphorylation.
- Pharmacological inhibition of key signaling enzymes (PI3-K, ROCK).
Main Results:
- VEGF treatment promotes redistribution of N-WASP to the cell surface, dependent on Nck.
- Nck plays a role in actin stress fiber formation.
- VEGF induces rapid phosphorylation of cofilin and LIM-kinase.
- PAK does not mediate VEGF-induced LIM-kinase phosphorylation or actin reorganization.
- PI3-K and ROCK signaling pathways are involved in regulating LIM-kinase activity.
Conclusions:
- VEGF regulates both actin polymerization and depolymerization through distinct signaling pathways.
- Nck and N-WASP are key mediators of VEGF-induced actin polymerization and stress fiber formation.
- VEGF-induced actin depolymerization involves cofilin and LIM-kinase, with PI3-K and ROCK playing regulatory roles.
- The PAK pathway is not involved in VEGF-induced actin reorganization in this context.