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Hrs regulates the endocytic sorting of the fibroblast growth factor receptor 2b

Francesca Belleudi1, Laura Leone, Maddalena Maggio

  • 1Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Medicina Sperimentale, Università di Roma La Sapienza, Rome, Italy. francesca.belleudi@uniroma1.it

Experimental Cell Research
|April 14, 2009
PubMed

Insights

Hrs regulates the degradation pathway of keratinocyte growth factor receptor (KGFR) but not its recycling. Hrs recruitment to KGFR after KGF treatment is crucial for degradation, not ligand-induced phosphorylation.

Area of Science:

  • Cell biology
  • Molecular and cell biology
  • Receptor tyrosine kinase signaling

Background:

  • Keratinocyte growth factor receptor (KGFR/FGFR2b) has distinct endocytic pathways regulated by ligands KGF/FGF7 and FGF10/KGF2.
  • Hrs is known to regulate the degradation of ubiquitinated receptor tyrosine kinases via endocytosis.
  • The role of Hrs in KGFR endocytosis and trafficking remains uninvestigated.

Purpose of the Study:

  • To investigate the role of Hrs in the alternative endocytic pathways of KGFR.
  • To determine if Hrs influences KGFR degradation or recycling.
  • To elucidate the mechanism of Hrs involvement in KGFR trafficking.

Main Methods:

  • Quantitative immunofluorescence microscopy
  • Biochemical analysis
  • Coimmunoprecipitation
  • siRNA interference

Main Results:

  • Hrs overexpression or depletion inhibits KGF-induced KGFR degradation by blocking lysosomal transport and promoting plasma membrane reappearance.
  • FGF10-induced KGFR recycling to the juxtanuclear compartment is unaffected by Hrs manipulation.
  • Hrs is recruited to KGFR upon KGF stimulation, independent of ligand-induced tyrosine phosphorylation.

Conclusions:

  • Hrs specifically regulates the degradative endocytic pathway of KGFR.
  • Hrs does not influence the FGF10-mediated juxtanuclear recycling pathway of KGFR.
  • Hrs recruitment to KGFR, rather than ligand-induced phosphorylation, appears essential for its function in regulating receptor degradation.

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