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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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Keratinocyte growth factor receptor ligands target the receptor to different intracellular pathways

Francesca Belleudi1, Laura Leone1, Valerio Nobili1

  • 1Dipartimento di Medicina Sperimentale, Università di Roma "La Sapienza", Viale Regina Elena 324, 00161 Roma, Italy.

Traffic (Copenhagen, Denmark)
|October 20, 2007
PubMed

Insights

Keratinocyte growth factor receptor (KGFR) trafficking differs based on ligand. KGF promotes KGFR degradation, while FGF10 directs it to recycling endosomes, impacting cell signaling.

Area of Science:

  • Cell biology
  • Molecular signaling

Background:

  • Keratinocyte growth factor receptor (KGFR)/fibroblast growth factor receptor 2b (FGFR2b) is activated by keratinocyte growth factor (KGF/FGF7) and FGF10/KGF2.
  • These ligands exhibit distinct requirements for heparan sulfate proteoglycans and heparin binding.

Purpose of the Study:

  • To investigate the differential endocytic trafficking of KGFR induced by KGF and FGF10.
  • To elucidate the downstream signaling consequences of ligand-specific receptor trafficking.

Main Methods:

  • Immunofluorescence and immunoelectron microscopy to visualize KGFR internalization and localization.
  • Confocal microscopy with endocytic markers and TSG101 silencing to track receptor fate.
  • Biochemical assays to assess KGFR ubiquitination, degradation, and substrate phosphorylation.

Main Results:

  • KGFR internalization by both KGF and FGF10 occurs via clathrin-coated pits.
  • KGF treatment leads to KGFR ubiquitination and degradation via the degradative pathway.
  • FGF10 treatment directs KGFR to recycling endosomes, associated with higher mitogenic activity.

Conclusions:

  • Ligand-dependent endocytic trafficking regulates KGFR fate.
  • FGF10-induced recycling correlates with enhanced mitogenic signaling compared to KGF.
  • Differential receptor trafficking dictates distinct functional outcomes of KGFR activation.

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