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

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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.

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Authors and Affiliations

  1. Cardiology Division, Department of Medicine, Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA

    Chunhong Gong, Konstantin V. Stoletov & Bruce I. Terman

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  1. Chunhong Gong
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  2. Konstantin V. Stoletov
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  3. Bruce I. Terman
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Correspondence to Bruce I. Terman.

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Gong, C., Stoletov, K.V. & Terman, B.I. VEGF treatment induces signaling pathways that regulate both actin polymerization and depolymerization. Angiogenesis 7, 313–322 (2004). https://doi.org/10.1007/s10456-004-7960-2

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  • DOI: https://doi.org/10.1007/s10456-004-7960-2

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