Angiogenesis

, Volume 7, Issue 4, pp 313–322

VEGF treatment induces signaling pathways that regulate both actin polymerization and depolymerization

  • Chunhong Gong
  • Konstantin V. Stoletov
  • Bruce I. Terman
Article

DOI: 10.1007/s10456-004-7960-2

Cite this article as:
Gong, C., Stoletov, K.V. & Terman, B.I. Angiogenesis (2004) 7: 313. doi:10.1007/s10456-004-7960-2

Abstract

The angiogenic growth factor vascular endothelial growth factor (VEGF) enhances endothelial cell migration through the activation of multiple signaling transduction pathways. Actin reorganization is an important component in VEGF-induced migration, yet the signaling pathways mediating this process remain unclear. Actin reorganization involves both actin polymerization and depolymerization, and in this study we demonstrate that VEGF-treatment regulates both of these activities. With respect to actin polymerization, our results indicate that the actin nucleation promoting factors (NPF) neural Wiskott–Aldrich syndrome protein (N-WASP) binds the SH2- plus SH3-domain containing adaptor protein Nck in both control and VEGF-treated cells. We had previously showed that VEGF treatment leads to the recruitment of Nck to activated receptor, and our current results indicate a VEGF-dependent redistribution of N-WASP to the cell surface. A Nck dominant-negative blocked Nck recruitment to receptor, blocked N-WASP cellular redistribution and attenuated actin stress fiber formation. With respect to actin depolymerization, VEGF-treatment led to the rapid phosphorylation of the actin depolymerization factor cofilin, and its upstream regulator, LIM-kinase (LIMK). Unlike what is observed in certain other cell types, the p21-activated kinase (PAK), a Nck binding protein, does not mediate VEGF-induced LIMK phosphorylation, as a PAK dominant-negative had no effect on this activity. The PAK dominant-negative also did not affect VEGF-induced actin reorganization. Pharmacological inhibitors of phosphoinositide-3 kinase (PI3-K) and the rho-activated kinase (ROCK) attenuated VEGF-induced LIMK phosphorylation, indicating a role for (PI3-K) and ROCK in the signaling pathways leading to regulation of LIMK activity.

Keywords

LactinangiogenesiscofilinKDRNckN-WASPVEGF

Copyright information

© Springer 2005

Authors and Affiliations

  • Chunhong Gong
    • 1
  • Konstantin V. Stoletov
    • 1
  • Bruce I. Terman
    • 1
  1. 1.Cardiology Division, Department of Medicine, Department of PathologyAlbert Einstein College of MedicineBronxUSA
  2. 2.Cardiology Division, Department of MedicineAlbert Einstein College of MedicineUSA