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NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

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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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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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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...
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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...
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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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Looking Down on NF-κB.

Leah M Williams1, Thomas D Gilmore2

  • 1Department of Biology, Boston University, Boston, Massachusetts, USA.

Molecular and Cellular Biology
|May 13, 2020
PubMed
Summary
This summary is machine-generated.

The NF-κB signaling pathway

Keywords:
NF-kappaBdevelopmentevolutioninnate immunitysignal transduction

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Area of Science:

  • Evolutionary biology
  • Molecular biology
  • Immunology

Background:

  • The NF-κB transcription factor family is crucial in immunity and development, well-studied in complex organisms.
  • Recent discoveries reveal NF-κB homologs in basal phyla like Cnidaria, Porifera, and protists.
  • Understanding basal NF-κBs offers insights into the pathway's evolutionary origins.

Purpose of the Study:

  • To review current knowledge on NF-κB in basal organisms.
  • To analyze the evolution and conservation of NF-κB sequences, domains, and regulatory mechanisms.
  • To explore the dual roles of NF-κB in development and immunity in simpler life forms.

Main Methods:

  • Comparative analysis of NF-κB sequences and domains across diverse taxa.
  • Review of existing literature on NF-κB function and regulation in basal invertebrates and protists.
  • Examination of structural and DNA-binding similarities between basal and mammalian NF-κBs.

Main Results:

  • Basal NF-κB proteins share structural and DNA-binding similarities with mammalian NF-κB p100.
  • Activation of basal NF-κBs exhibits characteristics of both canonical and noncanonical mammalian pathways.
  • Single NF-κB proteins in basal organisms appear to play dual roles in development and immunity.

Conclusions:

  • Investigating NF-κB in invertebrates illuminates the evolutionary history of this vital signaling pathway.
  • This research sheds light on the origins of regulated innate immunity.
  • Understanding basal NF-κB is relevant for assessing responses of key ecological organisms to environmental changes and diseases.