Integrin‐linked kinase is an essential mediator for T‐cadherin‐dependent signaling via Akt and GSK3β in endothelial cells
- 7 May 2007
- journal article
- Published by Wiley in The FASEB Journal
- Vol. 21 (12) , 3083-3095
- https://doi.org/10.1096/fj.06-7723com
Abstract
Glycosylphosphatidylinositol-anchored T-cadherin (T-cad) influences several parameters of angiogenesis including endothelial cell (EC) differentiation, migration, proliferation, and survival. This presupposes signal transduction networking via mediatory regulators and molecular adaptors since T-cad lacks transmembrane and cytosolic domains. Here, using pharmacological inhibition of PI3K, adenoviral-mediated T-cad-overexpression, siRNA-mediated T-cad-depletion, and agonistic antibody-mediated ligation, we demonstrate signaling by T-cad through PI3K-Akt-GSK3β pathways in EC. T-cad-overexpressing EC exhibited increased levels and nuclear accumulation of active β-catenin, which was transcriptionally active as shown by increased Lef/Tcf reporter activity and cyclin D1 levels. Cotransduction of EC with constitutively active GSK3β (S9A-GSK3β) abrogated the stimulatory effects of T-cad on active β-catenin accumulation, proliferation, and survival. Integrin-linked kinase (ILK), a membrane proximal upstream regulat...Keywords
Funding Information
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (3100A0–105406)
- Division of Engineering Education and Centers (LSHM‐CT‐2004)
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