Related Experiment Video

Updated: Jul 17, 2026

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

Utilizing protein phosphatase inhibitors to define PP2A as a regulator of ataxia-telangiectasia mutated

Aaron A Goodarzi1, Pauline Douglas, Greg B G Moorhead

  • 1Southern Alberta Cancer Research Institute and Department of Biochemistry & Molecular Biology, University of Calgary, AB, Canada.

Methods in Molecular Biology (Clifton, N.J.)
|January 4, 2007
PubMed

Insights

The study reveals that protein phosphatase 2A-like activity regulates the autophosphorylation of Ataxia-telangiectasia mutated (ATM) kinase, a key player in DNA double-strand break repair after radiation exposure.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Cellular Biology

Background:

  • Ataxia-telangiectasia mutated (ATM) is a critical serine/threonine kinase involved in DNA double-strand break (DSB) repair.
  • Ionizing radiation triggers ATM autophosphorylation at serine 1981, but regulatory mechanisms remain unclear.

Purpose of the Study:

  • To elucidate the specific protein phosphatase activity regulating ATM autophosphorylation at serine 1981.
  • To investigate the role of protein phosphatase 2A (PP2A)-like activity in ATM regulation.

Main Methods:

  • Cell treatment with okadaic acid, a protein phosphatase inhibitor.
  • Assays to quantify specific protein phosphatase activities.
  • Analysis of ATM autophosphorylation in response to phosphatase inhibition.

Main Results:

  • Protein phosphatase 2A-like activity was identified as a key regulator of ATM autophosphorylation on serine 1981.
  • Inhibition of PP2A-like activity affected ATM autophosphorylation dynamics.

Conclusions:

  • ATM autophosphorylation is modulated by a PP2A-like phosphatase activity.
  • This finding provides new insights into the intricate regulation of DNA damage response pathways.

More Related Videos

Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays09:36

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

Published on: August 13, 2017

A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors10:17

A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors

Published on: April 29, 2022

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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...