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Cell cycle-dependent phosphorylation of Disabled-2 by cdc2

Junqi He1, Jianguo Xu, Xiang-Xi Xu

  • 1Department of Pharmacology, Rollins Research Center, Emory University School of Medicine, Atlanta, GA 30322, USA.

Oncogene
|July 26, 2003
PubMed

Insights

Disabled-2 (Dab2) phosphorylation increases during mitosis, regulated by cyclin-dependent kinases like cdc2. This process impacts cell growth control and involves interactions with Pin1 for dephosphorylation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Disabled-2 (Dab2) is a signal transduction protein involved in cell growth control.
  • Dab2 is a phosphoprotein, but the kinases responsible for its phosphorylation are not well understood.

Purpose of the Study:

  • To identify the kinases that phosphorylate Dab2 during the cell cycle.
  • To elucidate the functional consequences of Dab2 phosphorylation by specific kinases.

Main Methods:

  • Cell cycle analysis of Dab2 phosphorylation.
  • Inhibition studies using roscovitine, a cyclin-dependent kinase inhibitor.
  • Coimmunoprecipitation assays to identify interacting kinases.
  • In vitro kinase assays using purified cdc2 and Dab2 fusion proteins.
  • Analysis of Dab2-Pin1 interactions.

Main Results:

  • Dab2 phosphorylation significantly increases during mitosis.
  • Roscovitine treatment blocks this increased phosphorylation.
  • Dab2 robustly coimmunoprecipitates with cyclin-dependent kinase cdc2.
  • Purified cdc2 phosphorylates Dab2 in vitro on multiple sites.
  • Mitotic phosphorylation of Dab2 by cdc2 promotes its association with Pin1, a peptidylprolyl isomerase.

Conclusions:

  • Dab2 is differentially phosphorylated during the cell cycle by cdc2.
  • This phosphorylation event by cdc2 influences Dab2 dephosphorylation via Pin1 interaction.
  • These findings suggest a regulatory feedback mechanism controlling Dab2's role in cell growth and proliferation.

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