Related Experiment Video

Updated: Oct 5, 2025

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

6.3K

Protein phosphatase 2A catalytic subunit β suppresses PMA/ionomycin-induced T-cell activation by negatively

Rui Gao1, Xin Li2, Huiying Gao1

  • 1State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, China.

The FEBS Journal
|January 24, 2022
PubMed

Insights

The catalytic subunit beta isoform of protein phosphatase 2A (PPP2CB) is not essential for T-cell development. However, its absence specifically enhances T-cell activation stimulated by phorbol myristate acetate plus ionomycin.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Precise regulation of T-cell activation is crucial for immune homeostasis.
  • Protein phosphatase 2A (PP2A) is vital for T-cell development and function.
  • The specific role of the PPP2CB catalytic subunit of PP2A in T-cells was previously unknown.

Purpose of the Study:

  • To investigate the function of the PPP2CB catalytic subunit of PP2A in T-cell development and activation.
  • To elucidate the mechanisms underlying PPP2CB's role in T-cell responses.

Main Methods:

  • Generation of T cell-specific PPP2CB knockout mice (PPP2CBfl/fl Lck-Cre+).
  • Analysis of T-cell development in thymus and peripheral lymphoid organs.
  • Assessment of T-cell activation via T-cell receptor (TCR) stimulation, cytokine stimulation, and phorbol myristate acetate (PMA) plus ionomycin stimulation.
  • Mechanistic studies involving phosphoinositide 3-kinase/Akt signaling pathway and calcium (Ca2+) flux analysis.
  • Inhibition studies using a PI3K inhibitor.
  • Mass spectrometry-based phospho-peptide analysis to identify PPP2CB substrates.

Main Results:

  • PPP2CB is dispensable for T-cell development in both thymus and peripheral lymphoid organs.
  • PPP2CB deletion did not affect TCR-induced T-cell activation or cytokine-induced T-cell responses.
  • PPP2CB deficiency specifically enhanced PMA plus ionomycin-induced T-cell activation, characterized by increased proliferation, CD69 and CD25 expression, and cytokine production (IFN-γ, IL-2, TNF).
  • Mechanistically, PPP2CB deletion enhanced phosphoinositide 3-kinase/Akt signaling and Ca2+ flux upon PMA plus ionomycin stimulation.
  • A PI3K inhibitor reversed the augmented T-cell activation in PPP2CB-deficient T cells.
  • Potential substrates of PPP2CB in T-cell activation were identified.

Conclusions:

  • PPP2CB plays a specific role in regulating T-cell activation, particularly in response to combined PMA and ionomycin stimulation.
  • The absence of PPP2CB potentiates T-cell activation by enhancing the PI3K/Akt pathway and Ca2+ flux.
  • These findings reveal a novel regulatory mechanism in T-cell activation controlled by PPP2CB.
Keywords:
PI3K/Akt signalingPMA plus ionomycinPPP2CBT-cell activation

More Related Videos

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

9.2K
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

6.8K

Related Concept Videos

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...
4.1K
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...
9.5K
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...
4.7K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
12.3K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.9K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.6K