Protein Kinase D1 Regulates VEGF-A-Induced αvβ3 Integrin Trafficking and Endothelial Cell Migration

Di Blasio, L., Droetto, S., Norman, J. , Bussolino, F. and Primo, L. (2010) Protein Kinase D1 Regulates VEGF-A-Induced αvβ3 Integrin Trafficking and Endothelial Cell Migration. Traffic, 11(8), pp. 1107-1118. (doi:10.1111/j.1600-0854.2010.01077.x)

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Publisher's URL: http://dx.doi.org/10.1111/j.1600-0854.2010.01077.x

Abstract

The bidirectional communication between integrin alpha v beta 3 and vascular endothelial growth factor (VEGF) receptors acts to integrate and coordinate endothelial cell (EC) activity during angiogenesis. However, the molecular mechanisms involved in this signaling crosstalk are only partially revealed. We have found that protein kinase D1 (PKD1) was activated by VEGF-A, but not by other angiogenic factors, and associated with alpha v beta 3 integrin. Moreover, knockdown of PKD1 increased endocytosis of alpha v beta 3 and reduced its return from endosomes to the plasma membrane leading to accumulation of the integrin in Rab5- and Rab4-positive endosomes. Consistent with this, PKD1 knockdown caused defects in focal complex formation and reduced EC migration in response to VEGF-A. Moreover, knockdown of PKD1 reduced EC motility on vitronectin, whereas migration on collagen I was not PKD1 dependent. These results suggest that PKD1-regulated alpha v beta 3 trafficking contributes to the angiogenesis process by integrating VEGF-A signaling with extracellular matrix interactions.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Norman, Professor James
Authors: Di Blasio, L., Droetto, S., Norman, J., Bussolino, F., and Primo, L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Traffic
ISSN:1398-9219

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