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Fibroblast growth factor receptor 3 induces gene expression primarily through Ras-independent signal transduction
D Y Choi1, J J Toledo-Aral, H Y Lin
1Department of Molecular Genetics and Microbiology, Institute of Cell and Developmental Biology, State University of New York at Stony Brook, Stony Brook, NY 11794-5222, USA.
The Journal of Biological Chemistry
|November 21, 2000
Summary
Fibroblast growth factor receptor-1 (FGFR-1) strongly induces neuronal phenotypes via Ras-dependent pathways. Fibroblast growth factor receptor-3 (FGFR-3) elicits neuronal changes through Ras-independent pathways, demonstrating distinct signaling mechanisms.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Signaling
Background:
- Fibroblast growth factors (FGFs) and their receptors (FGFRs) are crucial for development.
- Four FGFRs (FGFR-1-4) exist, and their signaling is key to cell differentiation.
- Understanding FGFR signaling pathways is vital for developmental biology.
Purpose of the Study:
- To compare the neuronal differentiation capabilities of FGFR-1 and FGFR-3.
- To investigate the signaling pathways utilized by FGFR-1 and FGFR-3 in PC12 cells.
- To determine if FGFR-3 can induce neuronal markers via Ras-independent pathways.
Main Methods:
- Utilized FGF-1 stimulation in PC12 cells.
- Compared neurite outgrowth induced by FGFR-1 and FGFR-3.
- Analyzed activation of Ras-dependent mitogen-activated protein kinase (MAPK) pathways.
- Assessed induction of Ras-independent neuronal markers (sodium channels, peripherin, Thy-1).
Main Results:
- FGFR-1 potently induced neurite outgrowth and sustained Ras-dependent MAPK activation.
- FGFR-3 showed weaker Ras-dependent signaling.
- FGFR-3 effectively induced Ras-independent neuronal gene expression (sodium channels, peripherin, Thy-1).
- FGFR-3's induction of these markers was equivalent to FGFR-1.
Conclusions:
- FGFR-1 elicits neuronal phenotypes primarily through robust, sustained Ras-dependent signaling.
- FGFR-3 induces neuronal phenotypic changes mainly via Ras-independent pathways.
- FGFRs utilize distinct signaling routes to control neuronal differentiation.
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