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 Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

6.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.2K
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

6.8K
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...
6.8K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

7.3K
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...
7.3K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

8.4K
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...
8.4K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

3.9K
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:
3.9K
GTPases and their Regulation02:14

GTPases and their Regulation

8.3K
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,...
8.3K

You might also read

Related Articles

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

Sort by
Same author

Tyrosine kinase inhibitors in Kosaki/Penttinen syndromes: new reports, follow-up of treated individuals and literature review.

European journal of human genetics : EJHG·2026
Same author

A genetic variant of adenylate cyclase 7 associated with ulcerative colitis shows impaired function and G-protein-coupled receptor signaling.

Human genetics·2026
Same author

Decoding splicing variants in high-throughput sequencing: a functional validation approach integrating deep learning tools.

European journal of human genetics : EJHG·2026
Same author

Neurodevelopmental Phenotypes and Brain Anomalies in Individuals With Heterozygous SEMA6A Variants.

Clinical genetics·2026
Same author

ADA2 genotype and enzyme activity may predict vasculitic or hematologic DADA2 phenotype.

Journal of human immunity·2026
Same author

GPR15-guided CD8<sup>+</sup> T regulatory cells control intestinal inflammation.

Nature·2026

Related Experiment Video

Updated: Jun 12, 2025

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
09:37

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Published on: August 25, 2021

1.7K

Germline mutations in a G protein identify signaling cross-talk in T cells.

Hyoungjun Ham1,2,3, Huie Jing1,2, Ian T Lamborn1,2,4

  • 1Human Immunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.

Science (New York, N.Y.)
|September 19, 2024
PubMed
Summary

Germline mutations in GNAI2, encoding Gαi2, cause impaired immunity and cell migration. Activating Gαi2 mutations disrupt T cell receptor signaling, impacting immune responses and cellular growth.

More Related Videos

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay
13:51

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay

Published on: November 11, 2018

9.8K
Studying TGF-&#946; Signaling and TGF-&#946;-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

12.8K

Related Experiment Videos

Last Updated: Jun 12, 2025

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
09:37

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Published on: August 25, 2021

1.7K
Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay
13:51

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay

Published on: November 11, 2018

9.8K
Studying TGF-&#946; Signaling and TGF-&#946;-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

12.8K

Area of Science:

  • Molecular Biology
  • Immunology
  • Genetics

Background:

  • Monogenic inborn errors reveal critical physiological pathways.
  • GNAI2 encodes Gαi2, a key component in G protein signal transduction.
  • Gαi2 is typically associated with adenylyl cyclase-mediated cyclic adenosine monophosphate (cAMP) production.

Purpose of the Study:

  • Investigate germline mutations in GNAI2.
  • Understand the role of Gαi2 in human physiology and disease.
  • Elucidate the impact of GNAI2 mutations on immune function and cell signaling.

Main Methods:

  • Analysis of germline mutations in GNAI2.
  • Assessment of clinical presentations in patients with GNAI2 mutations.
  • Investigation of cellular mechanisms including cell migration and T cell receptor (TCR) signaling.

Main Results:

  • Activating GNAI2 mutations were identified in patients with impaired immunity.
  • Mutant Gαi2 impaired cell migration and augmented TCR stimulation responses.
  • Mutant Gαi2 sequestered RASA2, promoting RAS activation and downstream signaling (ERK/MAPK, PI3K-AKT S6).

Conclusions:

  • Activating GNAI2 mutations disrupt normal immune function.
  • Gαi2 plays a significant role in regulating TCR signaling and cellular processes.
  • These findings highlight GNAI2 as a potential target for understanding and treating immune disorders.