TF/FVIIa transactivate PDGFRbeta to regulate PDGF-BB-induced chemotaxis in different cell types: involvement of Src and PLC
2008 (English)In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 28, no 1, 135-41 p.Article in journal (Refereed) Published
BACKGROUND: We have previously reported the potentiation of PDGF-BB-induced chemotaxis of fibroblasts, vascular smooth muscle cells, and endothelial cells by FVIIa. Here we studied the role of TF/FVIIa and the induced signaling pathways in regulation of chemotaxis of human monocytes, fibroblasts, and porcine aorta endothelial cells. METHODS AND RESULTS: Human monocytes were obtained by using Ficoll-Paque gradient and the MACS system (for highly purified population), fibroblasts and PAE cells have been characterized previously. Inhibitors of selected signaling intermediates were used, and the effect of TF/FVIIa on the migratory response of all cells to chemotactic agents was analyzed. The induced signaling was studied by immunoprecipitation and Western blotting. TF/FVIIa complex selectively enhanced PDGF-BB-induced chemotaxis in a Src-family, PLC, and PAR-2-dependent manner. Using PAE cells we identified c-Src and c-Yes as the Src-family members activated by TF/FVIIa. We report for the first time the PAR-2 and Src family-dependent transactivation of PDGFRbeta by TF/FVIIa involving phosphorylation of a subset of PDGFRbeta tyrosines. CONCLUSIONS: The described transactivation is a likely mechanism of TF/FVIIa-mediated regulation of PDGF-BB-induced chemotaxis. Similar behavior of 3 principally different cell types in our experimental setup may reflect a general function of TF in regulation of cell migration.
Place, publisher, year, edition, pages
2008. Vol. 28, no 1, 135-41 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-97675DOI: 10.1161/ATVBAHA.107.155754ISI: 000252159500020PubMedID: 17991872OAI: oai:DiVA.org:uu-97675DiVA: diva2:172706