TF/FVIIa transactivate PDGFRbeta to regulate PDGF-BB-induced chemotaxis in different cell types: involvement of Src and PLC.
Arterioscler Thromb Vasc Biol
; 28(1): 135-41, 2008 Jan.
Article
em En
| MEDLINE
| ID: mdl-17991872
ABSTRACT
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 ANDRESULTS:
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Derivado de Plaquetas
/
Tromboplastina
/
Fator VIIa
/
Quimiotaxia
/
Quinases da Família src
/
Receptor beta de Fator de Crescimento Derivado de Plaquetas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Suécia