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RSK2 regulates endocytosis of FGF receptor 1 by phosphorylation on serine 789

B Nadratowska-Wesolowska1, E M Haugsten1, M Zakrzewska2

  • 11] Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, Oslo, Norway [2] Department of Biochemistry, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo, Norway.

Oncogene
|October 22, 2013
PubMed

Insights

p90 ribosomal S6 kinase 2 (RSK2) directly interacts with and phosphorylates fibroblast growth factor receptor 1 (FGFR1). This interaction regulates FGFR1 signaling by modulating receptor endocytosis, offering new insights into FGFR1 regulation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Signal Transduction

Background:

  • Fibroblast growth factor receptor 1 (FGFR1) signaling is crucial for cellular functions like proliferation and migration.
  • Dysregulation of FGFR1 signaling is linked to various diseases, including human cancers.
  • Identifying novel regulators of FGFR1 is essential for understanding its role in pathology.

Purpose of the Study:

  • To identify novel regulators of fibroblast growth factor receptor 1 (FGFR1) signaling.
  • To elucidate the interaction between RSK2 and FGFR1 and its functional consequences.

Main Methods:

  • Yeast two-hybrid screens were employed to identify FGFR1 interaction partners.
  • In vitro and in vivo experiments were conducted to confirm the interaction and study its effects.
  • RSK2 activity and FGFR1 phosphorylation at serine 789 were manipulated to assess signaling outcomes.

Main Results:

  • p90 ribosomal S6 kinase 2 (RSK2) was identified as a novel interactor of FGFR1.
  • Phosphorylated RSK2 binds to and phosphorylates FGFR1 at serine 789.
  • Inhibition of RSK2 prolonged FGFR1 tyrosine transphosphorylation, reduced FGFR1 endocytosis and ubiquitination.

Conclusions:

  • RSK2 directly phosphorylates FGFR1 at serine 789, representing a novel regulatory mechanism.
  • RSK2-mediated FGFR1 phosphorylation modulates receptor signaling by regulating endocytosis and ubiquitination.
  • This finding provides a mechanistic explanation for prolonged FGFR1 signaling activity and has implications for cancer research.

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