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#fibroblast growth factor

2 public questions tagged with this topic.

Paracrine Factor

Which pathway is primarily activated by the binding of FGFs to their receptors?

FGFR activation recruits adaptor FRS2α leading to Grb2-SOS complex activating Ras-MAPK cascade, PI3K-AKT survival, plus direct PLCγ calcium release and STAT activation via scaffolds and direct phosphorylation. JAK-STAT pathway becomes engaged via STAT1,3,5 phosphorylation by FGFR kinase activity or associated Jak1/2 kinases, regulating chondrocyte growth arrest and immune genes SOCS3, p21. Although MAPK is primary developmental route for proliferation and patterning, JAK-STAT mediates FGFR3 dwarfism through STAT1 nuclear accumulation inhibiting cell cycle progression via Cip/Kip inhibitors. Wn

Ref: Powers et al., Endocrine Reviews: FGFR activation engages JAK-STAT downstream of FRS2 adaptor in chondrocytes.

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Paracrine Factor

Which receptor type is commonly associated with Fibroblast Growth Factor (FGF) signaling?

Fibroblast Growth Factors bind high-affinity Receptor Tyrosine Kinases FGFRs composed of extracellular three immunoglobulin loops, single transmembrane helix, intracellular split tyrosine kinase domain requiring dimerization. Ligand plus heparan sulfate proteoglycan induces dimerization and trans-autophosphorylation of activation loop tyrosines Y653/654 recruiting adaptor FRS2, activating Ras-MAPK, PI3K-AKT, PLCγ calcium release, and JAK-STAT effectors promoting survival, mitogenesis, migration. This RTK nature distinguishes FGF from Hedgehog which uses Patched-Smoothened seven-transmembrane,

Ref: Ornitz & Itoh, Genome Biology 2001: FGFs signal through receptor tyrosine kinases FGFR1-4 requiring heparan sulfate.

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