Critical role of protein kinase D in VEGF-induced vascular permeability and angiogenesis

Vascular endothelial growth factor (VEGF) is not only a powerful angiogenic factor but also a potent vascular permeability factor, which disrupts vascular barrier function in diseased tissues. In inflammatory and ischemia tissues, through impairing endothelial cell-cell junctions VEGF causes vascular permeability and edema, resulting in extensive injury to ischemic tissues after stroke or myocardial infarction. In cancer, VEGF-mediated disruption of the vascular barrier may potentiate tumour cell extravasation, resulting in widespread metastatic disease. All of these pathological conditions are also associated with increased angiogenesis. The OBJECTIVE of this study is to elucidate the signaling pathways whereby VEGF induces vascular permeability and angiogenesis. Emerging evidence from my group and others supports a crucial role of protein kinase D (PKD) in VEGF signaling and angiogenesis. PKD1 is a member of a novel family of serine/threonine protein kinases,which are potential druggable targets for the...