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Blood, 1 March 2006, Vol. 107, No. 5, pp. 1896-1902. Prepublished online as a Blood First Edition Paper on December 1, 2005; DOI 10.1182/blood-2005-04-1524. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-04-1524v1 107/5/1896    most recent Alert me when this article is cited 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Faraone, D. Articles by Facchiano, A. Search for Related Content PubMed PubMed Citation Articles by Faraone, D. Articles by Facchiano, A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Heterodimerization of FGF-receptor 1 and PDGF-receptor-: a novel mechanism underlying the inhibitory effect of PDGF-BB on FGF-2 in human cells Debora Faraone, Maria S. Aguzzi, Gianluca Ragone, Katia Russo, Maurizio C. Capogrossi, and Antonio Facchiano From the Laboratorio di Patologia Vascolare and the Laboratorio di Oncologia Molecolare, Istituto Dermopatico della Immacolata, IDI-IRCCS, Rome, Italy. Previous evidence has shown that platelet-derived growth factor-BB (PDGF-BB) and fibroblast growth factor-2 (FGF-2) directly interact with high affinity, leading to potent reciprocal inhibitory effects on bovine endothelial cells and rat vascular smooth muscle cells. In this study, we report that PDGF-BB inhibits a series of FGF-2–induced events, such as proliferation of human umbilical vein endothelial cells (HUVECs), FGF-2 cellular internalization, phosphorylation of intracellular signaling factors including p38, rac1/cdc42, MKK4, and MKK3/6, and phosphorylation of FGF-receptor 1 (FGF-R1). PDGF-receptor- (PDGF-R) was found to mediate PDGF-BB inhibitory effects because its neutralization fully restored FGF-2 mitogenic activity and internalization. Additional biochemical analyses, coimmunoprecipitation experiments, and FRET analysis showed that FGF-R1 and PDGF-R directly interact in vitro and in vivo and that this interaction is somehow increased in the presence of the corresponding ligands FGF-2 and PDGF-BB. These results suggest that FGF-R1/PDGF-R heterodimerization may represent a novel endogenous mechanism to modulate the action of these receptors and their ligands and to control endothelial cell function. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Mottet, A. Bellahcene, S. Pirotte, D. Waltregny, C. Deroanne, V. Lamour, R. Lidereau, and V. Castronovo Histone Deacetylase 7 Silencing Alters Endothelial Cell Migration, a Key Step in Angiogenesis Circ. Res., December 7, 2007; 101(12): 1237 - 1246. [Abstract] [Full Text] [PDF] L. S. Chaturvedi, H. M. Marsh, X. Shang, Y. Zheng, and M. D. Basson Repetitive Deformation Activates Focal Adhesion Kinase and ERK Mitogenic Signals in Human Caco-2 Intestinal Epithelial Cells through Src and Rac1 J. Biol. Chem., January 5, 2007; 282(1): 14 - 28. [Abstract] [Full Text] [PDF] W. Lederle, H.-J. Stark, M. Skobe, N. E. Fusenig, and M. M. Mueller Platelet-Derived Growth Factor-BB Controls Epithelial Tumor Phenotype by Differential Growth Factor Regulation in Stromal Cells Am. J. Pathol., November 1, 2006; 169(5): 1767 - 1783. [Abstract] [Full Text] [PDF]

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