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Related Concept Videos

MAPK Signaling Cascades01:07

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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...
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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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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.
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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...
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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.
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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
Summary
This summary is machine-generated.

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.

Keywords:
ERKJNKMAP kinaseTNFp38 MAP kinase

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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.