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Anchorage of VEGF to the extracellular matrix conveys differential signaling responses to endothelial cells

Anchorage of VEGF to the extracellular matrix conveys differential signaling responses to endothelial cells

Authors :
Tatiana Segura
M. Luisa Iruela-Arispe
Sean M. Anderson
Sunyoung Lee
Tom T. Chen
Alfonso Luque
Source :
The Journal of cell biology, vol 188, iss 4, The Journal of Cell Biology
Publication Year :
2010
Publisher :
eScholarship, University of California, 2010.

Abstract

Matrix-bound VEGF elicits more distinct vascular effects than soluble VEGF, including prolonged VEGFR2 activation with altered patterns of tyrosine activation and downstream enhancement of the p38/MAPK pathway.<br />VEGF can be secreted in multiple isoforms with variable affinity for extracellular proteins and different abilities to induce vascular morphogenesis, but the molecular mechanisms behind these effects remain unclear. Here, we show molecular distinctions between signaling initiated from soluble versus matrix-bound VEGF, which mediates a sustained level of VEGFR2 internalization and clustering. Exposure of endothelial cells to matrix-bound VEGF elicits prolonged activation of VEGFR2 with differential phosphorylation of Y1214, and extended activation kinetics of p38. These events require association of VEGFR2 with β1 integrins. Matrix-bound VEGF also promotes reciprocal responses on β1 integrin by inducing its association with focal adhesions; a response that is absent upon exposure to soluble VEGF. Inactivation of β1 integrin blocks the prolonged phosphorylation of Y1214 and consequent activation of p38. Combined, these results indicate that when in the context of extracellular matrix, activation of VEGFR2 is distinct from that of soluble VEGF in terms of recruitment of receptor partners, phosphorylation kinetics, and activation of downstream effectors.

Details

Database :
OpenAIRE
Journal :
The Journal of cell biology, vol 188, iss 4, The Journal of Cell Biology
Accession number :
edsair.doi.dedup.....237420459fd86d7b4fe17636b7e7f241