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Mol Biol Cell. 2010 Mar 1;21(5):687-90. doi: 10.1091/mbc.E09-07-0590.

Binding to the extracellular matrix and proteolytic processing: two key mechanisms regulating vascular endothelial growth factor action.

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1
Genentech, Inc., South San Francisco, CA 94080, USA. nf@gene.com

Abstract

Vascular endothelial growth factor (VEGF, VEGF-A) is a major regulator of physiological and pathological angiogenesis. One feature of VEGF is the existence of multiple isoforms arising from alternative exon splicing. Our initial biochemical and biological studies indicated that such isoforms are uniquely suited to generate angiogenic gradients by virtue of their differential ability to interact with the extracellular matrix (ECM). Although ECM-bound VEGF was bioactive, processing by physiologically relevant proteases such as plasmin was identified as a key mechanism to convert ECM-bound VEGF into freely diffusible forms. This retrospective article examines the early studies and also emphasizes the subsequent progress in our understanding of these processes in health and disease.

PMID:
20185770
PMCID:
PMC2828956
DOI:
10.1091/mbc.E09-07-0590
[Indexed for MEDLINE]
Free PMC Article
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