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Updated: Feb 3, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
Greatwall kinase at a glance
1Centre de Recherche de Biologie cellulaire de Montpellier (CRBM), CNRS UMR 5237, Université de Montpellier, 1919 Route de Mende, 34293 Montpellier cedex 5, France Thierry.lorca@crbm.cnrs.fr anna.castro@crbm.cnrs.fr.
Abstract:
Mitosis is controlled by a subtle balance between kinase and phosphatase activities that involve the master mitotic kinase cyclin-B-Cdk1 and its antagonizing protein phosphatase 2A-B55 (PP2A-B55). Importantly, the Greatwall (Gwl; known as Mastl in mammals, Rim15 in budding yeast and Ppk18 in fission yeast) kinase pathway regulates PP2A-B55 activity by phosphorylating two proteins, cAMP-regulated phosphoprotein 19 (Arpp19) and α-endosulfine (ENSA). This phosphorylation turns these proteins into potent inhibitors of PP2A-B55, thereby promoting a correct timing and progression of mitosis. In this Cell Science at a Glance article and the accompanying poster, we discuss how Gwl is regulated in space and time, and how the Gwl-Arpp19-ENSA-PP2A-B55 pathway plays an essential role in the control of M and S phases from yeast to human. We also summarize how Gwl modulates oncogenic properties of cells and how nutrient deprivation influences Gwl activity.
Insights
The Greatwall (Gwl) kinase pathway, through Arpp19 and ENSA proteins, inhibits PP2A-B55 phosphatase, ensuring proper cell division timing. This pathway is crucial for mitosis and is influenced by nutrients and cancer.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Mitosis regulation involves a balance between kinase and phosphatase activities.
- Cyclin-B-Cdk1 and PP2A-B55 are key regulators of mitotic progression.
- The Greatwall (Gwl) kinase pathway modulates PP2A-B55 activity.
Purpose of the Study:
- To elucidate the regulation of Gwl kinase in space and time.
- To understand the role of the Gwl-Arpp19-ENSA-PP2A-B55 pathway in cell cycle control.
- To explore Gwl's influence on oncogenic properties and nutrient deprivation.
Main Methods:
- Review of existing literature and research findings.
- Analysis of signaling pathways involved in mitosis.
- Discussion of Gwl's regulatory mechanisms and cellular functions.
Main Results:
- Gwl phosphorylates Arpp19 and ENSA, inhibiting PP2A-B55.
- This inhibition is critical for the timely progression of M and S phases.
- The Gwl pathway's activity is influenced by nutrient availability and cellular context.
Conclusions:
- The Gwl-Arpp19-ENSA-PP2A-B55 pathway is essential for accurate cell division across species.
- Gwl's modulation of this pathway impacts cell proliferation and oncogenesis.
- Understanding Gwl regulation offers insights into cell cycle control and cancer therapeutics.
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