Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

A gain-of-function mutation in STAT6.

C Daniel1, A Salvekar, U Schindler

  • 1Tularik Inc., South San Francisco, California 94080, USA.

The Journal of Biological Chemistry
|April 5, 2000
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

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

Sort by
Same author

Localization of O₂‑sensing ADO‑RGS pathway components in mouse and human kidneys under normoxia, hypoxia and renal fibrosis.

Pflugers Archiv : European journal of physiology·2026
Same author

Anti-BAFF treatment modulates intragraft fibrosis and DKK3 expression in a non-adherence model of experimental kidney transplantation.

Transplant immunology·2026
Same author

Determining Barriers to Dietary Change Among Medically Underserved Men With Prostate Cancer.

Health education & behavior : the official publication of the Society for Public Health Education·2026
Same author

Multimodal identification of a rare head and neck cancer patient cohort in the clinical data warehouse of Greater Paris Teaching Hospital.

ESMO real world data and digital oncology·2026
Same author

[Influence of smoking on the efficacy of immunotherapy in advanced lung cancers].

Revue des maladies respiratoires·2025
Same author

Real-world effectiveness and tolerability of sotorasib in patients with KRAS G12C-mutated metastatic non-small cell lung cancer: The IFCT-2102 Lung KG12Ci study.

European journal of cancer (Oxford, England : 1990)·2025
Same journal

Correction: Characterization of Mast2 kinase defines structural features, regulation, and substrates.

The Journal of biological chemistry·2026
Same journal

Isotope-Edited ESEEM: A New Method for Probing Copper Binding Sites in Neurodegenerative Proteins.

The Journal of biological chemistry·2026
Same journal

Introduction to the Thematic Review Series on Intracellular Protein Degradation. The ubiquitous biology of intracellular protein degradation: a tribute to Alfred L. ("Fred") Goldberg.

The Journal of biological chemistry·2026
Same journal

Correction: Aromatic residue-rich amino-terminal segments of temporin L self-assemble into collagen-mimetic peptides with cell-adhesion properties.

The Journal of biological chemistry·2026
Same journal

YhbO is a DJ-1 family glyoxalase and α-oxoaldehyde hydratase that confers resistance to reactive carbonyl stress (112).

The Journal of biological chemistry·2026
Same journal

ARMH3 acts as a central scaffold at the Golgi/TGN through interactions with Arl5, GBF1, and PI4KB.

The Journal of biological chemistry·2026
See all related articles

A novel STAT6 mutant (STAT6VT) activates genes without Interleukin-4 (IL-4) stimulation. This discovery suggests mutations in STAT6 could predispose individuals to atopic diseases like asthma.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Interleukin-4 (IL-4) is a key cytokine in asthma and allergic disease pathogenesis.
  • IL-4 signaling primarily involves the Signal Transducer and Activator of Transcription 6 (STAT6) pathway.
  • STAT6 activation is critical for IL-4-induced gene expression.

Purpose of the Study:

  • To identify and characterize a STAT6 mutant activated independently of IL-4.
  • To investigate the mechanism of STAT6 mutant activation.
  • To explore the potential role of such mutations in atopic disease predisposition.

Main Methods:

  • Site-directed mutagenesis to create STAT6VT mutant with two amino acid changes in the SH2 domain.
  • Overexpression of STAT6VT in mammalian cells.

Related Experiment Videos

  • Assessment of STAT6VT tyrosine phosphorylation, DNA binding, and transcriptional activity.
  • Utilizing a Jak1- and Jak3-deficient fibroblast cell line (U4A) to identify the responsible kinase.

    • Main Results:

    • STAT6VT exhibits constitutive activation, including tyrosine phosphorylation, DNA binding, and transcription, independent of IL-4.
    • The STAT6VT mutant is phosphorylated by an IL-4-independent tyrosine kinase not capable of activating wild-type STAT6.
    • Mutations in the STAT6 SH2 domain alter protein structure and stability, leading to hyperactivation.

    Conclusions:

    • Specific mutations in STAT6 can lead to its hyperactivation and constitutive downstream gene expression.
    • This hyperactivation mechanism, driven by IL-4-independent kinases, offers a potential explanation for genetic predisposition to atopic diseases.
    • Further in vivo studies are warranted to confirm the role of STAT6 mutations in the etiology of allergic conditions.