Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

NF-κB-dependent Signaling Pathway

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...

Inflammatory Bowel Disease III: Crohn's Disease

Inflammatory Bowel Disease III: Crohn's Disease

Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...

Inflammatory Response

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...

The JAK-STAT Signaling Pathway

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...

Covalently Linked Protein Regulators

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.

Nitric Oxide Signaling Pathway

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Beyond PVR: dynamic physiologic assessment enhances prognostic evaluation in pulmonary hypertension associated with chronic obstructive pulmonary disease.

BMJ open respiratory research·2026

Same author

Stiff Left Atrial Syndrome: Hemodynamic Insights and a Noninvasive Diagnostic Approach.

Annals of the American Thoracic Society·2026

Same author

Right Ventricular End-Ejection Pressure Predicts Mortality in Patients With Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction.

Comprehensive Physiology·2026

Same author

Comparative Pulmonary Artery Pressure Response between Large-Bore Thrombectomy and Catheter-Directed Thrombolysis in Patients with Intermediate-High- and High-Risk Pulmonary Embolism.

Journal of vascular and interventional radiology : JVIR·2026

Same author

Reply to Sbarra et al.

American journal of physiology. Heart and circulatory physiology·2026

Same author

Pre-capillary Pulmonary Hypertension in a Patient with Interlobular Septal Thickening and Prominent Mediastinal Lymphadenopathy.

Annals of the American Thoracic Society·2026

Search research articles

Related Experiment Video

Updated: May 7, 2026

Chemiluminescence-based Assays for Detection of Nitric Oxide and its Derivatives from Autoxidation and Nitrosated Compounds

Chemiluminescence-based Assays for Detection of Nitric Oxide and its Derivatives from Autoxidation and Nitrosated Compounds

Published on: February 16, 2022

STAT3 regulation by S-nitrosylation: implication for inflammatory disease.

Jinsu Kim¹, Je-Seong Won, Avtar K Singh

¹1 Department of Pediatrics, Medical University of South Carolina , Charleston, South Carolina.

Antioxidants & Redox Signaling

|September 26, 2013

Summary

Nitric oxide (NO) regulates the Janus-activated kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway by modifying STAT3. This S-nitrosylation of STAT3 inhibits its phosphorylation, impacting immune responses and cell proliferation.

Related Experiment Videos

Last Updated: May 7, 2026

Chemiluminescence-based Assays for Detection of Nitric Oxide and its Derivatives from Autoxidation and Nitrosated Compounds

Chemiluminescence-based Assays for Detection of Nitric Oxide and its Derivatives from Autoxidation and Nitrosated Compounds

Published on: February 16, 2022

Area of Science:

Biochemistry
Cell Biology
Immunology

Background:

Redox-based modifications, including S-nitrosylation and S-glutathionylation, are emerging as critical signaling mechanisms.
The Janus-activated kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway is crucial in immune responses, inflammation, and tumorigenesis.

Purpose of the Study:

To investigate the S-nitrosylation-based regulation of the JAK2/STAT3 pathway.
To determine the role of nitric oxide (NO) in modulating STAT3 activity in microglia.

Main Methods:

Stimulation of microglia to induce S-nitrosylation and S-glutathionylation of STAT3.
Assessment of STAT3 phosphorylation (Tyr(705)) and downstream gene expression.
Cell-free kinase assays using purified JAK2 and STAT3.
Site-directed mutagenesis to identify the target cysteine residue (Cys(259)) in STAT3.

Main Results:

STAT3 undergoes both S-nitrosylation and S-glutathionylation in stimulated microglia.
S-nitrosylation, mediated by inducible nitric oxide synthase (iNOS)-produced NO or S-nitrosoglutathione (GSNO), inhibits STAT3 phosphorylation at Tyr(705).
GSNO inhibits STAT3 phosphorylation via S-nitrosylation at Cys(259), not by affecting JAK2 activity.
Inhibition of STAT3 phosphorylation leads to reduced microglial proliferation and associated gene expression, including IL-6 signaling.

Conclusions:

STAT3 activity is regulated by NO-mediated S-nitrosylation, specifically at Cys(259).
This post-translational modification of STAT3 impacts inflammatory and immune responses, as well as cell proliferation.
Targeting STAT3 S-nitrosylation presents a potential therapeutic strategy for diseases involving inflammation, immune dysregulation, and cancer.