Heterodimerization of FGF-receptor 1 and PDGF-receptor-α: 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, Antonio Facchiano

Research output: Contribution to journalArticlepeer-review

Abstract

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-α (PDGF-Rα) 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-Rα 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-Rα heterodimerization may represent a novel endogenous mechanism to modulate the action of these receptors and their ligands and to control endothelial cell function.

Original languageEnglish
Pages (from-to)1896-1902
Number of pages7
JournalBlood
Volume107
Issue number5
DOIs
Publication statusPublished - Mar 1 2006

ASJC Scopus subject areas

  • Hematology

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