Related Experiment Video

Updated: Jun 25, 2026

NF-κB-dependent Luciferase Activation and Quantification of Gene Expression in Salmonella Infected Tissue Culture Cells
10:57

NF-κB-dependent Luciferase Activation and Quantification of Gene Expression in Salmonella Infected Tissue Culture Cells

Published on: January 12, 2020

RhoA GTPase activation by TLR2 and TLR3 ligands: connecting via Src to NF-kappa B

Maria Manukyan1, Perihan Nalbant, Sylvia Luxen

  • 1Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|March 7, 2009
PubMed

Insights

Toll-like receptor (TLR) signaling activates RhoA, a key regulator of cell responses. This study shows RhoA is crucial for NF-kappaB activation downstream of TLRs and Src kinases, but not for type I IFN production.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Signaling

Background:

  • Rho GTPases, including RhoA, are critical regulators of immune receptor signaling.
  • Toll-like receptors (TLRs) activate host cells upon microbial structure recognition, involving RhoA.
  • The precise signaling pathway linking TLRs to RhoA activation remains unclear.

Purpose of the Study:

  • To elucidate the role of RhoA in TLR2 and TLR3 signaling pathways.
  • To investigate the upstream regulators and downstream effectors of RhoA activation in response to TLR stimulation.
  • To determine RhoA's involvement in specific immune responses, such as NF-kappaB activation and type I interferon generation.

Main Methods:

  • Utilized lung epithelial cells to study TLR2 and TLR3 signaling.
  • Investigated the recruitment and activation of RhoA at receptor-proximal cellular compartments.
  • Assessed the dependency of RhoA activity on Src family kinases and TLR adapters.
  • Examined the requirement of RhoA and Src kinases for NF-kappaB and type I IFN production.

Main Results:

  • Demonstrated TLR2- and TLR3-triggered recruitment and activation of RhoA in lung epithelial cells.
  • Established that RhoA activation is dependent on TLR-mediated stimulation of Src family kinases.
  • Confirmed that both Src family kinases and RhoA are essential for NF-kappaB activation.
  • Found that RhoA is dispensable for type I interferon generation.

Conclusions:

  • RhoA acts downstream of MyD88-dependent and -independent TLR signaling.
  • RhoA functions as a molecular switch in pathways initiated by TLR-Src interactions.
  • RhoA plays a specific role in NF-kappaB activation, distinct from its role in type I IFN production.

More Related Videos

Detection of Neu1 Sialidase Activity in Regulating TOLL-like Receptor Activation09:04

Detection of Neu1 Sialidase Activity in Regulating TOLL-like Receptor Activation

Published on: September 7, 2010

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF311:44

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

Related Concept Videos

Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
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 heterodimer of NF-κB...
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...
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...
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 are of three kinds RI, RII, and RIII. The RI...
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...