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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
- 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.
- Subjects :
- Vascular Endothelial Growth Factor A
Sus scrofa
p38 Mitogen-Activated Protein Kinases
Medical and Health Sciences
Extracellular matrix
Mice
0302 clinical medicine
Protein Isoforms
Internalization
Cells, Cultured
Research Articles
media_common
0303 health sciences
Cultured
biology
Integrin beta1
Biological Sciences
Endocytosis
Cell biology
Extracellular Matrix
Vascular endothelial growth factor A
Protein Transport
030220 oncology & carcinogenesis
Phosphorylation
Collagen
Signal transduction
Signal Transduction
Protein Binding
CD29
Protein Structure
media_common.quotation_subject
Cells
1.1 Normal biological development and functioning
Integrin
Article
Focal adhesion
03 medical and health sciences
Animals
Humans
Antigens
030304 developmental biology
Focal Adhesions
Endothelial Cells
Kinase insert domain receptor
Cell Biology
Vascular Endothelial Growth Factor Receptor-2
Protein Structure, Tertiary
Enzyme Activation
Kinetics
biology.protein
Tyrosine
Tertiary
Developmental Biology
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- The Journal of cell biology, vol 188, iss 4, The Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....237420459fd86d7b4fe17636b7e7f241