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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.
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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...
NF-kB-dependent Signaling Pathway02:26

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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 are of three kinds RI, RII, and RIII. The RI...
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Related Experiment Video

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Development and Application of Rapamycin-regulated Tyrosine Phosphatases
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Published on: September 6, 2024

SHARPIN negatively associates with TRAF2-mediated NFκB activation.

Yanhua Liang1

  • 1Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, United States of America. liangdoctor@163.com

Plos One
|August 11, 2011
PubMed
Summary
This summary is machine-generated.

SHARPIN’s role in NFκB signaling is complex. While it can activate NFκB (Nuclear Factor kappa B) in vitro, in vivo studies suggest it may also inhibit this pathway by interacting with proteins like TRAF2.

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Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
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Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Nuclear Factor kappa B (NFκB) is a critical transcription factor regulating immunity, inflammation, and development.
  • SHARPIN's role in NFκB activation is contradictory, with in vitro studies showing activation and in vivo findings suggesting inhibition.

Purpose of the Study:

  • To investigate the dual role of SHARPIN in NFκB signaling.
  • To identify SHARPIN-interacting proteins involved in NFκB regulation.

Main Methods:

  • Mass spectrometry to identify SHARPIN-binding proteins in various cell types.
  • Luciferase-based NFκB reporter assays to assess SHARPIN's effect on NFκB activity.
  • Confirmation of SHARPIN-TRAF2 interaction using immunoprecipitation.

Main Results:

  • Identified 17 proteins interacting with SHARPIN, including TRAF2.
  • Confirmed SHARPIN-TRAF2 interaction, consistent with previous reports.
  • Demonstrated that SHARPIN negatively regulates NFκB activation, an effect partially reversed by TRAF2 overexpression.

Conclusions:

  • SHARPIN exhibits a dual role in NFκB signaling, potentially activating it via ubiquitin ligase complexes and inhibiting it through interactions with downstream effectors like TRAF2.
  • These findings reconcile conflicting in vivo and in vitro data on SHARPIN's function in NFκB pathways.