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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.
Abstract:
Fibroblast growth factor receptors (FGFR) are widely expressed in many tissues and cell types, and the temporal expression of these receptors and their ligands play important roles in the control of development. There are four FGFR family members, FGFR-1-4, and understanding the ability of these receptors to transduce signals is central to understanding how they function in controlling differentiation and development. We have utilized signal transduction by FGF-1 in PC12 cells to compare the ability of FGFR-1 and FGFR-3 to elicit the neuronal phenotype. In PC12 cells FGFR-1 is much more potent in the induction of neurite outgrowth than FGFR-3. This correlated with the ability of FGFR-1 to induce robust and sustained activation of the Ras-dependent mitogen-activated protein kinase pathways. In contrast, FGFR-3 could not induce strong sustained Ras-dependent signals. In this study, we analyzed the ability of FGFR-3 to induce the expression of sodium channels, peripherin, and Thy-1 in PC12 cells because all three of these proteins are known to be induced via Ras-independent pathways. We determined that FGFR-3 was capable of inducing several Ras-independent gene expression pathways important to the neuronal phenotype to a level equivalent of that induced by FGFR-1. Thus, FGFR-3 elicits phenotypic changes primarily though activation of Ras-independent pathways in the absence of robust Ras-dependent signals.
Insights
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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