The central role of VEGF (vascular endothelial growth factor A) in angiogenesis is dependent upon its ability to co-ordinately regulate multiple endothelial functions. The multifunctionality of VEGF at the cellular level results from its ability to initiate a diverse, complex and integrated network of signalling pathways via its major receptor, kinase-insert-domain-containing receptor (KDR). Activation of phospholipase C-γ, protein kinase C, Ca2+, ERK (extracellular-signal-regulated protein kinase), Akt, Src, focal adhesion kinase and calcineurin pathways has been implicated in mediating multiple VEGF functions, including survival, proliferation, migration, vascular permeability, tubulogenesis, NO and prostanoid synthesis, and gene expression. NO and prostanoids in turn play paracrine and autocrine roles in linking post-receptor signalling to biological functions. Integration between biologically important signalling cascades occurs at several points. Akt and ERK, for example, are key junction points linking together signal transduction involved in survival and NO generation, and proliferation and prostanoid biosynthesis. Together, the multiplicity, functional versatility and integration of VEGF signalling provide a useful framework for understanding the mechanisms underlying the endothelial biological response to this key factor.
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December 2003
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Conference Article|
December 01 2003
VEGF signalling: integration and multi-tasking in endothelial cell biology
I. Zachary
I. Zachary
1
Department of Medicine, University College London, 5 University Street, London WC1E 6JJ, U.K.
1To whom correspondence should be addressed (e-mail I.Zachary@ucl.ac.uk).
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Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2003 Biochemical Society
2003
Biochem Soc Trans (2003) 31 (6): 1171–1177.
Citation
I. Zachary; VEGF signalling: integration and multi-tasking in endothelial cell biology. Biochem Soc Trans 1 December 2003; 31 (6): 1171–1177. doi: https://doi.org/10.1042/bst0311171
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