negative regulation of fibroblast growth factor receptor signaling pathway

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of fibroblast growth factor receptor signaling pathway activity. [GOC:go_curators]

Negative regulation of fibroblast growth factor receptor (FGFR) signaling pathway is a crucial cellular process that fine-tunes the activity of this essential signaling cascade. FGFRs are transmembrane receptors that bind to fibroblast growth factors (FGFs) and initiate downstream signaling events, which control a wide range of cellular processes, including proliferation, differentiation, migration, and survival. Dysregulation of FGFR signaling can lead to various diseases, including cancer, developmental disorders, and fibrosis.

To ensure proper cellular function, FGFR signaling must be tightly regulated. Negative regulation involves multiple mechanisms that act at different levels of the signaling pathway, from ligand binding and receptor activation to downstream signaling events.

**Key mechanisms of negative regulation:**

* **Ligand sequestration and degradation:** FGFs are sequestered by heparan sulfate proteoglycans (HSPGs) in the extracellular matrix, reducing their availability for binding to FGFRs. FGFs can also be degraded by proteases.
* **Inhibition of receptor dimerization and activation:** Certain proteins, such as Sprouty proteins and Fibroblast growth factor receptor inhibitors (FGFRI), interfere with FGFR dimerization and activation, preventing the formation of active receptor complexes.
* **Internalization and degradation of activated receptors:** After ligand binding, FGFRs undergo endocytosis and are either recycled back to the cell surface or targeted for lysosomal degradation. This process reduces the number of active receptors.
* **Downstream signaling inhibition:** Several intracellular proteins, including phosphatases, ubiquitin ligases, and inhibitors of downstream signaling molecules, act to attenuate the signaling cascade at various points. For example, protein tyrosine phosphatases (PTPs) dephosphorylate activated FGFRs, reducing their activity.
* **Transcriptional regulation of FGFR expression:** The expression of FGFRs is tightly regulated at the transcriptional level by various transcription factors and signaling pathways, ensuring appropriate levels of receptor expression.
* **MicroRNA regulation:** MicroRNAs can target FGFR mRNAs, leading to their degradation or translational repression, further regulating FGFR levels.

**Overall, negative regulation of FGFR signaling pathway involves a complex network of molecular mechanisms that act in concert to fine-tune FGFR signaling activity and ensure appropriate cellular responses.**'
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Proteins (2)

Compounds (6)