negative regulation of macrophage colony-stimulating factor signaling pathway

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of macrophage colony-stimulating factor signaling pathway. [GOC:TermGenie, PMID:16705167]

Negative regulation of macrophage colony-stimulating factor (M-CSF) signaling pathway is a complex process that involves a series of molecular events that suppress the activation of the M-CSF signaling pathway. M-CSF is a growth factor that stimulates the proliferation, differentiation, and survival of macrophages. The M-CSF signaling pathway is initiated when M-CSF binds to its receptor, c-Fms, on the surface of macrophages. This binding event triggers a cascade of intracellular signaling events, ultimately leading to the activation of transcription factors that regulate the expression of genes involved in macrophage function.

The negative regulation of this pathway is crucial for maintaining normal macrophage homeostasis and preventing excessive inflammation. Several mechanisms contribute to the negative regulation of M-CSF signaling, including:

**1. Desensitization of the c-Fms receptor:** Prolonged exposure to M-CSF can lead to desensitization of the c-Fms receptor. This occurs through receptor downregulation, where the receptors are internalized and degraded, or through receptor phosphorylation, which can inhibit receptor signaling.

**2. Inhibitory signaling pathways:** Several intracellular signaling pathways can negatively regulate M-CSF signaling. These pathways include the PI3K/AKT pathway, the MAPK pathway, and the STAT pathway. These pathways can act at different levels in the signaling cascade, inhibiting the activation of downstream signaling molecules.

**3. Expression of inhibitory proteins:** Certain proteins can directly inhibit the M-CSF signaling pathway. For example, the protein SHIP1 can dephosphorylate PIP3, a key signaling molecule in the PI3K pathway, thereby inhibiting PI3K signaling.

**4. Feedback loops:** Negative feedback loops can regulate M-CSF signaling. For example, the transcription factor STAT5, which is activated by M-CSF signaling, can also induce the expression of genes that encode inhibitory proteins, creating a negative feedback loop.

Overall, the negative regulation of M-CSF signaling pathway is a critical process for maintaining macrophage homeostasis and preventing excessive inflammation. This complex process involves various mechanisms, including receptor desensitization, inhibitory signaling pathways, expression of inhibitory proteins, and feedback loops. These mechanisms work together to ensure that M-CSF signaling is appropriately regulated and that macrophages function correctly.'
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Proteins (1)

Compounds (30)