This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 28/1/135    most recent ATVBAHA.107.155754v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Siegbahn, A. Articles by Velling, T. Search for Related Content PubMed PubMed Citation Articles by Siegbahn, A. Articles by Velling, T.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:135.)
© 2008 American Heart Association, Inc.

Cell Biology/Signaling

TF/FVIIa Transactivate PDGFRβ to Regulate PDGF-BB–Induced Chemotaxis in Different Cell Types

Involvement of Src And PLC

Agneta Siegbahn; Matilda Johnell; Anna Nordin; Mikael Åberg; Teet Velling

From the Department of Medical Sciences, Clinical Chemistry, Uppsala University, Sweden.

Correspondence to Agneta Siegbahn or Teet Velling, Department of Medical Sciences, Clinical Chemistry, Academic Hospital, SE-751 85 Uppsala, Sweden. E-mail agneta.siegbahn{at}medsci.uu.se or teet.velling@medsci.uu.se

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 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 PDGFRβ by TF/FVIIa involving phosphorylation of a subset of PDGFRβ 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.

TF/FVIIa was found to selectively potentiate the PDGF-BB–induced chemotaxis of 3 principally different cell types. We provide data concerning the signaling pathways involved in this potentiation, and describe the TF/FVIIa-induced, PAR-2, c-Src, and c-Yes–dependent transactivation of PDGFRβ as a likely mechanism of its regulation.

Key Words: TF/FVIIa • PDGFRβ • transactivation • cell signaling • chemotaxis

This article has been cited by other articles:

				H. Lei, G. Velez, P. Hovland, T. Hirose, D. Gilbertson, and A. Kazlauskas Growth Factors Outside the PDGF Family Drive Experimental PVR Invest. Ophthalmol. Vis. Sci., July 1, 2009; 50(7): 3394 - 3403. [Abstract] [Full Text] [PDF]

				H. Lei and A. Kazlauskas Growth Factors Outside of the Platelet-derived Growth Factor (PDGF) Family Employ Reactive Oxygen Species/Src Family Kinases to Activate PDGF Receptor {alpha} and Thereby Promote Proliferation and Survival of Cells J. Biol. Chem., March 6, 2009; 284(10): 6329 - 6336. [Abstract] [Full Text] [PDF]

				S.K. Payeli, R. Latini, C. Gebhard, A. Patrignani, U. Wagner, T.F. Luscher, and F.C. Tanner Prothrombotic Gene Expression Profile in Vascular Smooth Muscle Cells of Human Saphenous Vein, but Not Internal Mammary Artery Arterioscler. Thromb. Vasc. Biol., April 1, 2008; 28(4): 705 - 710. [Abstract] [Full Text] [PDF]