Related Experiment Video

Updated: Aug 8, 2025

A Macrophage Reporter Cell Assay to Examine Toll-Like Receptor-Mediated NF-kB/AP-1 Signaling on Adsorbed Protein Layers on Polymeric Surfaces
07:55

A Macrophage Reporter Cell Assay to Examine Toll-Like Receptor-Mediated NF-kB/AP-1 Signaling on Adsorbed Protein Layers on Polymeric Surfaces

Published on: January 7, 2020

7.5K

p38δ controls Mitogen- and Stress-activated Kinase-1 (MSK1) function in response to toll-like receptor activation in

Ester Díaz-Mora1, Diego González-Romero1, Marta Meireles-da-Silva1

  • 1Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC (CNB-CSIC), Madrid, Spain.

Frontiers in Cell and Developmental Biology
|February 27, 2023
PubMed

Insights

p38δ, another p38 Mitogen-Activated Kinase (MAPK), activates Mitogen- and Stress-activated Kinase (MSK) 1 in macrophages. This activation influences inflammatory molecule production in the innate immune response.

Area of Science:

  • Cellular and Molecular Immunology
  • Signal Transduction Pathways
  • Innate Immune Response

Background:

  • Mitogen- and Stress-activated Kinase (MSK) 1 is a nuclear protein regulating cytokine production in macrophages.
  • MSK1 activation is known to be mediated by p38α Mitogen-Activated Kinase (MAPK) and extracellular signal-regulated kinase (ERK1/2).

Purpose of the Study:

  • To investigate the role of p38δ MAPK in the activation of MSK1 in macrophages.
  • To elucidate the downstream effects of p38δ-mediated MSK1 activation on inflammatory gene expression.

Main Methods:

  • Utilized knockout macrophage cell lines and specific kinase inhibitors.
  • Performed in vitro phosphorylation and activation assays with recombinant kinases.
  • Analyzed the phosphorylation of transcription factors CREB and ATF1.
  • Quantified the expression of MSK-dependent genes, including DUSP1 and IL-1Ra mRNA.

Main Results:

  • Identified p38δ MAPK as a mediator of MSK1 phosphorylation and activation in LPS-stimulated macrophages, alongside p38α and ERK1/2.
  • Demonstrated that recombinant p38δ activates MSK1 in vitro to a similar extent as p38α.
  • Observed impaired phosphorylation of CREB and ATF1, and reduced expression of DUSP1 and IL-1Ra mRNA in p38δ-deficient macrophages.

Conclusions:

  • p38δ MAPK plays a significant role in MSK1 activation within macrophages.
  • MSK1 activation by p38δ contributes to the regulation of inflammatory gene expression involved in the innate immune response.
Keywords:
MAPKMSK1macrophagesp38δ/p38γphosphorylation

More Related Videos

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

7.5K
Isolation of Murine Peritoneal Macrophages to Carry Out Gene Expression Analysis Upon Toll-like Receptors Stimulation08:21

Isolation of Murine Peritoneal Macrophages to Carry Out Gene Expression Analysis Upon Toll-like Receptors Stimulation

Published on: April 29, 2015

36.7K

Related Concept Videos

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...
5.8K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.8K
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...
9.1K
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...
6.4K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.5K
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...
3.8K