Related Experiment Video

Updated: May 18, 2026

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
11:38

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Published on: September 14, 2021

Signal transduction pathways in chronic inflammatory autoimmune disease: small GTPases

Kris A Reedquist1, Paul P Tak

  • 1Division of Clinical Immunology and Rheumatology, Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, The Netherlands.

The Open Rheumatology Journal
|October 3, 2012
PubMed

Insights

Small GTPases are vital signaling proteins regulating immune cell responses. Dysregulation of these proteins is implicated in chronic inflammatory diseases like rheumatoid arthritis and lupus, suggesting new therapeutic targets.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cellular Signaling

Background:

  • Ras superfamily small GTPases are conserved intracellular signaling proteins.
  • They act as critical checkpoints linking receptor stimulation to cellular responses.
  • These proteins regulate diverse cellular processes including proliferation, survival, and trafficking.

Purpose of the Study:

  • To review the role of Ras, Rap, and Rho family GTPases in chronic inflammatory diseases.
  • To highlight recent advances in understanding GTPase pathway alterations in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).
  • To discuss potential therapeutic strategies targeting small GTPases.

Main Methods:

  • Literature review of small GTPase function in immune and stromal cells.
  • Analysis of evidence linking GTPase signaling to RA and SLE pathology.
  • Exploration of emerging therapeutic approaches for GTPase-related diseases.

Main Results:

  • Small GTPases critically coordinate immune and stromal cell interactions during inflammation.
  • Altered small GTPase signaling contributes to the pathogenesis of RA and SLE.
  • Specific Ras, Rap, and Rho family members are key players in these inflammatory conditions.

Conclusions:

  • Small GTPases are central to cellular responses in chronic inflammatory diseases.
  • Targeting small GTPase pathways offers promising therapeutic avenues for RA and SLE.
  • Further research into GTPase biology can lead to novel treatments for autoimmune disorders.
Keywords:
GTPasesfarnesyltransferase inhibitors.matrix metalloproteinasessystemic lupus erythematosus

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

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...
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...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

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 the...
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...
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:
GTPases and their Regulation02:14

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...