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Ubiquitination of fibroblast growth factor receptor 1 is required for its intracellular sorting but not for its

Ellen Margrethe Haugsten1, Jedrzej Malecki, Sunniva Maria Stordal Bjørklund

  • 1Centre for Cancer Biomedicine, Faculty Division Norwegian Radium Hospital, University of Oslo, 0310 Oslo, Norway.

Molecular Biology of the Cell
|May 16, 2008
PubMed

Insights

Receptor ubiquitination is not essential for fibroblast growth factor receptor (FGFR) internalization but is crucial for its lysosomal degradation. Impaired ubiquitination leads to sustained signaling due to altered receptor sorting.

Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • Endocytosis and lysosomal degradation of growth factor receptors are critical cellular processes.
  • Ubiquitination of the intracellular domain of receptors is implicated in these pathways.

Purpose of the Study:

  • To investigate the role of fibroblast growth factor receptor (FGFR) ubiquitination in its internalization and intracellular sorting.
  • To determine if ubiquitination is required for FGFR endocytosis and lysosomal targeting.

Main Methods:

  • Construction and analysis of multiple fibroblast growth factor receptor 1 (FGFR1) mutants with lysine residues in the intracellular domain substituted with arginines.
  • Assessment of tyrosine kinase activity, ubiquitination status, endocytosis, and lysosomal degradation of FGFR1 mutants.

Main Results:

  • Mutants with all intracellular lysines substituted lost tyrosine kinase activity.
  • Active multilysine FGFR1 mutants showed reduced ubiquitination but normal internalization.
  • These mutants were poorly degraded and sorted to recycling endosomes, leading to sustained signaling.

Conclusions:

  • Receptor ubiquitination is not required for FGFR endocytosis.
  • Ubiquitination is essential for the efficient lysosomal degradation and termination of FGFR signaling.
  • Altered receptor sorting due to impaired ubiquitination results in prolonged signaling duration.

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