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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
Published on: June 15, 2017
Down-regulation of platelet-derived growth factor receptor signaling during myogenesis
T Fiaschi1, P Chiarugi, F Buricchi
1Dipartimento di Scienze Biochimiche, Università di Firenze, viale Morgagni 50, 50134 Firenze, Italy.
Abstract:
Cell differentiation is often associated with a block in the cell cycle. Growth factor signaling has been reported to be impaired in differentiated cells, due to the withdrawal of growth factors or to transcriptional down-regulation of their receptors. Our proposal is that the down regulation of growth factor signaling may be achieved through an alternative pathway: the decrease of growth factor receptor activation and the ensuing inhibition of intracellular pathways leading the cell to division. Here we report that platelet-derived growth factor receptor (PDGFr) signaling is down-regulated during muscle differentiation, although its expression level remains unchanged. PDGFr signaling inhibition is achieved through a decrease in the receptor tyrosine phosphorylation level, in particular of Tyr716, Tyr751, Tyr857 and Tyr1021, leading to down-regulation of intracellular signaling pathways. Furthermore, during myogenesis, the expression level of several phosphotyrosine phosphatases (PTPs) increases and most of them shift toward the reduced/activated state. We propose a causal link between the down-regulation of PDGFr tyrosine phosphorylation and the increases in PTP specific activity during myogenesis.
Insights
Muscle cell differentiation involves decreased platelet-derived growth factor receptor (PDGFr) signaling, not by changing receptor levels, but by reducing receptor phosphorylation. This is linked to increased phosphotyrosine phosphatase (PTP) activity.
Area of Science:
- Cell biology
- Molecular signaling
Background:
- Cell differentiation often halts cell cycle progression.
- Growth factor signaling impairment in differentiated cells is known.
- Mechanisms include growth factor withdrawal or receptor downregulation.
Purpose of the Study:
- Investigate alternative pathways for growth factor signaling downregulation during differentiation.
- Propose that decreased receptor activation inhibits cell division pathways.
- Focus on platelet-derived growth factor receptor (PDGFr) signaling in muscle differentiation.
Main Methods:
- Studied PDGFr signaling during muscle differentiation (myogenesis).
- Assessed PDGFr expression levels and tyrosine phosphorylation.
- Examined phosphotyrosine phosphatase (PTP) expression and activity.
Main Results:
- PDGFr signaling decreased during myogenesis without changing receptor expression.
- Inhibition occurred via reduced PDGFr tyrosine phosphorylation (Tyr716, Tyr751, Tyr857, Tyr1021).
- Increased PTP expression and activation were observed during myogenesis.
Conclusions:
- PDGFr signaling is downregulated during muscle differentiation through reduced receptor phosphorylation.
- Increased PTP activity is causally linked to PDGFr dephosphorylation.
- This provides an alternative mechanism for inhibiting cell division signaling during differentiation.
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