Related Experiment Video

Updated: Aug 21, 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

Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A

Aaron A Goodarzi1, Jyoti C Jonnalagadda, Pauline Douglas

  • 1Department of Biological Sciences, University of Calgary, Calgary, AB, Canada.

The EMBO Journal
|October 29, 2004
PubMed

Insights

Okadaic acid triggers ataxia-telangiectasia mutated (ATM) kinase autophosphorylation by inhibiting protein phosphatase 2A (PP2A). This suggests PP2A regulates ATM activity in undamaged cells, independent of DNA damage.

Area of Science:

  • Cellular biology
  • Molecular oncology
  • DNA damage response

Background:

  • The precise mechanisms regulating ataxia-telangiectasia mutated (ATM) protein kinase activation remain incompletely understood.
  • Ionizing radiation (IR) is known to induce ATM autophosphorylation on serine 1981.

Purpose of the Study:

  • To investigate the role of protein phosphatases in regulating ATM activation in the absence of DNA damage.
  • To elucidate the interaction between ATM and protein phosphatase 2A (PP2A).

Main Methods:

  • Treatment of cells with okadaic acid (OA), a protein phosphatase inhibitor.
  • Assessment of ATM autophosphorylation and gamma-H2AX foci formation.
  • Co-immunoprecipitation assays to study protein interactions.
  • Measurement of protein phosphatase activity in ATM immunoprecipitates.

Main Results:

  • Okadaic acid induced ATM autophosphorylation on serine 1981 in unirradiated cells.
  • OA did not induce gamma-H2AX foci, indicating ATM activation independent of DNA double-strand breaks.
  • ATM was shown to interact with both scaffolding (A) and catalytic (C) subunits of PP2A in undamaged cells.
  • IR treatment led to the dissociation of PP2A from ATM, accompanied by a loss of associated protein phosphatase activity.

Conclusions:

  • Protein phosphatase 2A (PP2A) plays a significant role in regulating ATM autophosphorylation and activity in vivo.
  • PP2A may act as a negative regulator of ATM in undamaged cells.
  • Understanding PP2A-ATM interactions provides new insights into the control 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

Development and Application of Rapamycin-regulated Tyrosine Phosphatases06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

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...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
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,...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...