Joshi, Manjunath B. and Kyriakakis, Emmanouil and Pfaff, Dennis and Rupp, Katharina and Philippova, Maria and Erne, Paul and Resink, Thérèse J.. (2009) Extracellular cadherin repeat domains EC1 and EC5 of T-cadherin are essential for its ability to stimulate angiogenic behavior of endothelial cells. The FASEB Journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 23. pp. 4011-4021.
Full text not available from this repository.
Official URL: http://edoc.unibas.ch/dok/A6003722
Downloads: Statistics Overview
Abstract
T-cadherin (T-cad) promotes survival, proliferation, and migration of endothelial cells and induces angiogenesis. We aimed to identify domains of T-cad functionally relevant to its effects on endothelial cell behavior. To specifically target the functional properties of the 5 cadherin repeat domains (EC1-EC5) of T-cad, endothelial cells were transduced with lentivectors containing specific T-cad-domain-deletion mutant constructs (DeltaI, DeltaII, DeltaIII, DeltaIV, DeltaV). Empty (E) lentivector-transduced cells served as control. Similarly to overexpression of native T-cad, cells expressing DeltaII, DeltaIII, or DeltaIV displayed elevated levels of p-Akt and p-GSK3beta and increased proliferation rates (for DeltaII, DeltaIII) vs. E. DeltaI- and DeltaV-transduced cells exhibited reduced levels of p-Akt and p-GSK3beta and retarded growth rates vs. E. Stimulatory effects of native T-cad overexpression on Akt and GSK3beta phosphorylation were dose dependently inhibited by coexpression of DeltaI or DeltaV. Subsequent functional analyses compared only DeltaI-, DeltaII-, and DeltaV-mutant constructs with E as a negative control. Unlike DeltaII cells, DeltaI and DeltaV cells failed to exhibit homophilic ligation and deadhesion responses on a substratum of T-cad protein. In the wound assay, migration was increased for DeltaII cells but impaired for DeltaI and DeltaV cells. In endothelial cell-spheroid assay, angiogenic sprouting was augmented for DeltaII cells but inhibited for DeltaI and DeltaV cells. We conclude that EC1 and EC5 domains of T-cad are essential for its proangiogenic effects. DeltaI and DeltaV constructs may serve as dominant-negative mutants and as potential tools targeting excessive angiogenesis.
Faculties and Departments: | 03 Faculty of Medicine > Departement Biomedizin > Further Research Groups at DBM > Signal Transduction (Resink/Erne) |
---|---|
UniBasel Contributors: | Resink, Thérèse J. and Erne, Paul |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
Publisher: | FASEB |
ISSN: | 0892-6638 |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Related URLs: | |
Identification Number: |
|
Last Modified: | 24 May 2013 09:21 |
Deposited On: | 24 May 2013 09:02 |
Repository Staff Only: item control page