Protein phosphatase 2A (PP2A) is increased in old murine B cells and mediates p38 MAPK/tristetraprolin

Related Experiment Video

Updated: Jun 15, 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

Daniela Frasca1, Maria Romero, Ana Marie Landin

  • 1Department of Microbiology and Immunology, University of Miami Miller School of Medicine, P.O. Box 016960 (R-138), Miami, FL 33101, USA.

Mechanisms of Ageing and Development
|March 12, 2010
PubMed

Insights

Aging B cells show decreased immunoglobulin class switch due to reduced E47 mRNA stability. Increased protein phosphatase 2A (PP2A) activity in aged cells enhances tristetraprolin (TTP) binding to E47 mRNA, promoting its degradation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Aging Research

Background:

  • Immunoglobulin class switch is crucial for B cell function.
  • Age-related decline in B cell function is a significant health concern.
  • E47 transcription factor and tristetraprolin (TTP) regulate mRNA stability and B cell responses.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying age-related E47 mRNA instability in B cells.
  • To investigate the role of protein phosphatase 2A (PP2A) in regulating TTP activity and E47 mRNA stability in aging B cells.

Main Methods:

  • Analysis of E47 mRNA stability in young and aged murine splenic B cells.
  • Measurement of TTP expression, phosphorylation, and binding to E47 mRNA.
  • Assessment of PP2A activity and its effect on p38 MAPK and TTP phosphorylation.

Main Results:

  • E47 mRNA stability is reduced in aged B cells.
  • TTP mRNA and protein levels are elevated in aged B cells, with decreased phosphorylation.
  • PP2A activity is increased in aged B cells, leading to hypophosphorylation of p38 MAPK and TTP.
  • Hypophosphorylated TTP exhibits increased binding to E47 mRNA, accelerating its degradation.

Conclusions:

  • Increased PP2A activity in aged B cells contributes to E47 mRNA instability via enhanced TTP binding.
  • This mechanism partially explains the age-related decrease in immunoglobulin class switch in B cells.
  • Targeting PP2A or TTP phosphorylation may offer strategies to restore B cell function in aging individuals.

More Related Videos

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

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

Protein Transfection of Mouse Lung04:21

Protein Transfection of Mouse Lung

Published on: May 15, 2013

Related Concept Videos

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...
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...
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.
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...
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...
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...