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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
Summary
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.