Related Experiment Video

Updated: Jul 8, 2026

Microinjection of Recombinant RCAS(A) Retrovirus into Embryonic Chicken Lens
04:58

Microinjection of Recombinant RCAS(A) Retrovirus into Embryonic Chicken Lens

Published on: September 1, 2023

Regulation of protein serine-threonine phosphatase type-2A by tyrosine phosphorylation

J Chen1, B L Martin, D L Brautigan

  • 1Division of Biology and Medicine, Brown University, Providence, RI 02912.

Science (New York, N.Y.)
|August 28, 1992
PubMed

Insights

Type-2A protein phosphatase (PP2A) deactivates protein kinases. Phosphorylation of PP2A by tyrosine kinases on Tyr307 can transiently deactivate it, potentially enhancing cell signaling.

Area of Science:

  • Cellular Biology
  • Biochemistry
  • Signal Transduction

Background:

  • Extracellular signals initiating cell growth activate protein kinase cascades.
  • Protein kinases are regulated by phosphorylation and dephosphorylation.
  • Type-2A protein phosphatase (PP2A) is a key enzyme that dephosphorylates and deactivates protein kinases.

Purpose of the Study:

  • To investigate the regulation of PP2A activity by phosphorylation.
  • To identify the specific kinases that phosphorylate PP2A.
  • To determine the functional consequence of PP2A phosphorylation on cellular signaling.

Main Methods:

  • In vitro phosphorylation assays using purified PP2A catalytic subunit.
  • Treatment with phosphatase inhibitors like okadaic acid.
  • Use of thioadenosine triphosphate to create a thiophosphorylated protein resistant to autodephosphorylation.
  • Identification of phosphorylation sites using mass spectrometry.
  • Enzymatic assays to measure PP2A activity.
  • In vitro kinase assays using various tyrosine-specific protein kinases.

Main Results:

  • The catalytic subunit of PP2A is phosphorylated by tyrosine-specific protein kinases.
  • Phosphorylation occurs exclusively on tyrosine residue 307 (Tyr307).
  • Phosphorylation by kinases such as p60v-src, p56lck, epidermal growth factor receptor, and insulin receptor was observed.
  • PP2A activity was significantly reduced (>90%) when thiophosphorylated, indicating autodephosphorylation resistance.
  • Okadaic acid enhanced phosphorylation, suggesting an autodephosphorylation component.
  • Transient deactivation of PP2A was proposed as a mechanism.

Conclusions:

  • PP2A activity can be transiently regulated by phosphorylation on Tyr307 by specific tyrosine kinases.
  • This phosphorylation event leads to a loss of PP2A activity.
  • Transient deactivation of PP2A may play a role in modulating kinase cascade signaling pathways.
  • Understanding PP2A regulation provides insights into cellular growth and signal transmission.

More Related Videos

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation08:00

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation

Published on: October 4, 2024

Enzymatic Modification and Flow Cytometry Assessment of Yeast Surface Displayed Proteins10:54

Enzymatic Modification and Flow Cytometry Assessment of Yeast Surface Displayed Proteins

Published on: May 30, 2025

Related Concept Videos

Allosteric Regulation01:08

Allosteric Regulation

Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
Allosteric Regulation01:08

Allosteric Regulation

Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...
RNA Editing02:23

RNA Editing

RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
Regulation of Metabolism01:19

Regulation of Metabolism

Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and...
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,...