Related Experiment Video

Updated: May 2, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

951

TNF and MAP kinase signalling pathways

Guadalupe Sabio1, Roger J Davis2

  • 1Department of Vascular Biology and Inflammation, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain.

Seminars in Immunology
|March 21, 2014
PubMed

Insights

Tumor necrosis factor α (TNFα) signaling activates mitogen-activated protein (MAP) kinases, which then regulate inflammatory cytokine production. This review details how MAP kinases function both upstream and downstream in TNFα receptor signaling pathways.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Tumor necrosis factor α (TNFα) is a key cytokine in inflammation and immunity.
  • TNFα binding to its receptor initiates complex intracellular signaling cascades.
  • Mitogen-activated protein (MAP) kinases are crucial mediators of cellular responses to external stimuli.

Purpose of the Study:

  • To review the mechanisms by which MAP kinases are activated by TNFα.
  • To elucidate the role of MAP kinases in regulating inflammatory gene expression downstream of TNFα.
  • To understand the dual role of MAP kinases as both upstream and downstream components of TNFα signaling.

Main Methods:

  • Literature review of studies investigating TNFα signaling pathways.
  • Analysis of research on MAP kinase activation (ERK, JNK, p38) in response to TNFα.
  • Examination of data on cytokine gene expression modulated by MAP kinases.

Main Results:

  • TNFα receptor engagement activates ERK, JNK, and p38 MAP kinase pathways.
  • Activated MAP kinases induce secondary responses, including increased expression of inflammatory cytokines like TNFα.
  • MAP kinases operate both upstream and downstream in the intricate TNFα signaling network.

Conclusions:

  • MAP kinases are central regulators of the cellular response to TNFα.
  • Understanding these mechanisms is vital for targeting inflammatory diseases.
  • The dual role of MAP kinases highlights their importance in feedback loops within TNFα signaling.
Keywords:
ERKJNKMAP kinaseTNFp38 MAP kinase

More Related Videos

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development09:32

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

Published on: June 15, 2017

8.0K
Phospho Flow Cytometry with Fluorescent Cell Barcoding for Single Cell Signaling Analysis and Biomarker Discovery08:38

Phospho Flow Cytometry with Fluorescent Cell Barcoding for Single Cell Signaling Analysis and Biomarker Discovery

Published on: October 4, 2018

20.8K

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...
7.3K
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...
4.7K
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...
7.6K
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...
7.2K
NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

2.0K
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
64.6K