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Decorin regulates endothelial cell motility on collagen I through activation of insulin-like growth factor I receptor and modulation of α2β1 integrin activity

Fiedler, Lorna, Schonherr, Elke Helga, Waddington, Rachel J. ORCID: https://orcid.org/0000-0001-5878-1434, Niland, Stephan, Seidler, Daniela G., Aeschlimann, Daniel ORCID: https://orcid.org/0000-0003-0930-7706 and Eble, Johannes A. 2008. Decorin regulates endothelial cell motility on collagen I through activation of insulin-like growth factor I receptor and modulation of α2β1 integrin activity. Journal of Biological Chemistry 283 (25) , pp. 17406-17415. 10.1074/jbc.M710025200

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Abstract

The proteoglycan decorin is expressed by sprouting but not quiescent endothelial cells, and angiogenesis is dysregulated in its absence. Previously, we have shown that decorin core protein can bind to and activate insulin-like growth factor-I receptor (IGF-IR) in endothelial cells. In this study, we show that decorin promotes α2β1 integrin-dependent endothelial cell adhesion and migration on fibrillar collagen type I. We provide evidence that decorin modulates cell-matrix interaction in this context by stimulating cytoskeletal and focal adhesion reorganization through activation of the IGF-IR and the small GTPase Rac. Further, the glycosaminoglycan moiety of decorin interacts with α2β1, but not α1β1 integrin, at a site distinct from the collagen I-binding A-domain, to allosterically modulate collagen I-binding activity of the integrin. We propose that induction of decorin expression in angiogenic, as opposed to quiescent, endothelial cells promotes a motile phenotype in an interstitial collagen I-rich environment by both signaling through IGF-IR and influencing α2β1 integrin activity.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Subjects: Q Science > QD Chemistry
Q Science > QH Natural history > QH301 Biology
Publisher: American Society for Biochemistry and Molecular Biology
ISSN: 0021-9258
Last Modified: 02 Mar 2024 16:30
URI: https://orca.cardiff.ac.uk/id/eprint/5940

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