RRC ID 39923
Author Hayashi H, Ishisaki A, Suzuki M, Imamura T.
Title BMP-2 augments FGF-induced differentiation of PC12 cells through upregulation of FGF receptor-1 expression.
Journal J Cell Sci
Abstract When exposed to various neurotrophic factors, including fibroblast growth factors (FGF)-1 and -2, rat pheochromocytoma-derived PC12 cells differentiate into sympathetic neuron-like cells possessing elongated neurites. We found that while bone morphogenetic protein-2 (BMP-2) exerted little effect by itself on the differentiation of PC12 cells, in combination with FGF it strongly induced neurite outgrowth, even at subthreshold concentrations of FGF. Analysis of gene expression revealed that FGF receptor-1 (FGFR-1) mRNA was abundantly expressed in PC12 cells and that its expression was upregulated by pretreating the cells with BMP-2. Crosslinking the receptors with (125)I-FGF-2 and then immunoprecipitating them confirmed that expression of FGFR-1, but not other FGF receptor types, was enhanced by BMP-2. Furthermore, Scatchard analyses revealed that the numbers of FGF-2 binding sites were increased by approximately 40% after BMP-2 treatment. Pretreatment with BMP-2 also enhanced peak and sustained levels of FGF-induced ERK1/2 phosphorylation in PC12 cells. Finally, the augmentation of neurotrophic activity by BMP-2 was inhibited by SU5402, an FGFR-1 inhibitor. These findings indicate that BMP-2 augments FGF-induced differentiation of PC12 cells through selective upregulation of FGFR-1 expression, and suggest that BMP-2 and FGF act in concert to regulate cell differentiation in the nervous system.
Volume 114(Pt 7)
Pages 1387-95
Published 2001-4-1
DOI 10.1242/jcs.114.7.1387
PMID 11257004
MeSH Animals Bone Morphogenetic Protein 2 Bone Morphogenetic Proteins / metabolism* Bone Morphogenetic Proteins / pharmacology Cell Differentiation* DNA-Binding Proteins / pharmacology Enzyme Activation Enzyme Inhibitors / pharmacology Fibroblast Growth Factor 1 Fibroblast Growth Factor 2 / metabolism Fibroblast Growth Factor 2 / pharmacology Humans Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases / metabolism Nerve Growth Factor / pharmacology Neurites / physiology PC12 Cells Peptides / pharmacology Pyrroles / pharmacology RNA, Messenger Rats Receptor Protein-Tyrosine Kinases / antagonists & inhibitors Receptor Protein-Tyrosine Kinases / genetics Receptor Protein-Tyrosine Kinases / metabolism* Receptor, Fibroblast Growth Factor, Type 1 Receptors, Fibroblast Growth Factor / antagonists & inhibitors Receptors, Fibroblast Growth Factor / genetics Receptors, Fibroblast Growth Factor / metabolism* Signal Transduction / physiology* Smad7 Protein Trans-Activators / pharmacology Transforming Growth Factor beta* Up-Regulation*
IF 4.573
Times Cited 26
Human and Animal Cells PC-12(RCB0009)