Related Experiment Video

Updated: Aug 9, 2026

Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays
09:36

Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays

Published on: August 13, 2017

Activation of type-1 protein phosphatase by cdc2 kinase

E Villa-Moruzzi1

  • 1Department of Biomedicine, University of Pisa, Italy.

FEBS Letters
|June 15, 1992
PubMed

Insights

Cell division kinase 2 (cdc2) activates protein phosphatase 1 (PP1) by phosphorylating its inhibitor, inhibitor-2 (I2). This activation is linked to I2 phosphorylation, suggesting a key regulatory mechanism in cell cycle control.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Protein phosphatase 1 (PP1) is a crucial enzyme involved in numerous cellular processes.
  • PP1 activity is tightly regulated by various mechanisms, including regulatory subunits and phosphorylation.
  • The role of cell division kinase 2 (cdc2) in PP1 regulation was not fully understood.

Purpose of the Study:

  • To investigate the mechanism by which cdc2 activates PP1.
  • To determine if cdc2-mediated phosphorylation of inhibitor-2 (I2) is involved in PP1 activation.
  • To compare PP1 activation by cdc2 with activation by other kinases like FA/GSK3.

Main Methods:

  • Purification of cdc2 and PP1-inhibitor-2 complex from HeLa and skeletal muscle cells.
  • Enzymatic assays to measure PP1 activity.
  • Phosphorylation studies using cdc2 and inhibitor-2, and PP1 catalytic subunit.
  • Inhibition studies using EDTA and 5,6-dichlorobenzimidazole riboside.

Main Results:

  • Purified cdc2, alone or with p13suc1, activated inactive PP1 (catalytic subunit.inhibitor-2 complex).
  • PP1 activation by cdc2 was accompanied by phosphorylation of inhibitor-2 (I2).
  • Both PP1 activation and I2 phosphorylation increased in parallel during cdc2 incubation and decreased upon cdc2 inhibition.
  • cdc2 also phosphorylated the catalytic subunit of PP1, independent of I2.

Conclusions:

  • cdc2 directly activates PP1 through phosphorylation of inhibitor-2.
  • Phosphorylation of I2 is a key event mediating cdc2-induced PP1 activation.
  • This mechanism highlights a novel regulatory pathway for PP1 activity by the cell cycle kinase cdc2.

More Related Videos

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...