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Tyrosine phosphatase SHP-2 is a regulator of p27(Kip1) tyrosine phosphorylation

Irini Tossidou1, Marc Dangers, Alexandra Koch

  • 1Nephrologie, Medizinische Hochschule Hannover (MHH), Hannover, Germany.

Cell Cycle (Georgetown, Tex.)
|December 11, 2008
PubMed

Insights

The tyrosine phosphatase SHP-2 dephosphorylates the cell cycle regulator p27(Kip1), impacting its stability and cell cycle progression. This study identifies SHP-2 as a key regulator of p27(Kip1) tyrosine phosphorylation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Tyrosine phosphorylation of p27(Kip1) is critical for cell cycle regulation.
  • Src and Bcr-Abl mediate p27(Kip1) phosphorylation, but the dephosphorylation process remains uncharacterized.

Purpose of the Study:

  • To identify the tyrosine phosphatase responsible for p27(Kip1) dephosphorylation.
  • To investigate the role of SHP-2 in regulating p27(Kip1) activity and cell cycle progression.

Main Methods:

  • Co-immunoprecipitation assays to detect protein interactions.
  • Western blotting to assess phosphorylation status.
  • Small interfering RNA (siRNA) to inhibit SHP-2 expression.
  • In vitro phosphatase assays.

Main Results:

  • SHP-2 associates with p27(Kip1) and the G-CSF receptor, translocating to the nucleus upon G-CSF stimulation.
  • SHP-2 mediates the tyrosine dephosphorylation of p27(Kip1) in promyelocytic leukemia cells.
  • SHP-2 activation by G-CSF leads to specific in vitro dephosphorylation of p27(Kip1).
  • SHP-2 modulates p27(Kip1) stability and promotes cell cycle progression.

Conclusions:

  • SHP-2 is a critical phosphatase regulating p27(Kip1) tyrosine phosphorylation.
  • SHP-2 plays a significant role in G-CSF-mediated cell cycle control via p27(Kip1) modulation.

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