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 journalArticle

35 Citations (Scopus)

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

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Fibroblast Growth Factor 1
Platelet-Derived Growth Factor Receptors
Fibroblast Growth Factor Receptors
Fibroblast Growth Factor 2
Cells
Endothelial cells
Phosphorylation
Endothelial Cells
Ligands
Human Umbilical Vein Endothelial Cells
Vascular Smooth Muscle
Smooth Muscle Myocytes
Muscle
Rats
platelet-derived growth factor BB
Experiments

ASJC Scopus subject areas

  • Hematology

Cite this

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. / Faraone, Debora; Aguzzi, Maria S.; Ragone, Gianluca; Russo, Katia; Capogrossi, Maurizio C.; Facchiano, Antonio.

In: Blood, Vol. 107, No. 5, 01.03.2006, p. 1896-1902.

Research output: Contribution to journalArticle

Faraone, Debora ; Aguzzi, Maria S. ; Ragone, Gianluca ; Russo, Katia ; Capogrossi, Maurizio C. ; Facchiano, Antonio. / 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. In: Blood. 2006 ; Vol. 107, No. 5. pp. 1896-1902.
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