Related Experiment Video
Updated: Jul 8, 2026
09:09
Removal and Replacement of Endogenous Ligands from Lipid-Bound Proteins and Allergens
Published on: February 24, 2021
Essential role for Gab2 in the allergic response.
1Cancer Biology Program, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA hgu@caregroup.harvard.edu.
Nature
|July 13, 2001
Summary
Gab2 is crucial for mast cell responses to IgE receptor activation. Mice lacking Gab2 show impaired allergic reactions, highlighting Gab2 as a key activator of PI(3)K signaling in immunity.
Area of Science:
- Immunology
- Cell signaling
- Molecular biology
Background:
- Dos/Gab family proteins act as scaffolds, binding signal relay molecules like Shp-2 and PI(3)K.
- These adapters are involved in signal transduction pathways initiated by growth factors, cytokines, and antigen receptors.
- While Gab1 knockout mice exhibit embryonic lethality, Gab2 knockout mice are viable.
Purpose of the Study:
- To investigate the role of Gab2 in immune responses, specifically in mast cells.
- To determine Gab2's function in the signaling cascade initiated by the high-affinity IgE receptor (FcεRI).
- To explore the therapeutic potential of targeting Gab2 in allergic diseases.
Main Methods:
- Generation and phenotypic analysis of Gab2 knockout (Gab2-/-) mice.
- Assessment of mast cell degranulation and cytokine gene expression upon FcεRI stimulation.
- Biochemical analysis of PI(3)K signaling pathways in wild-type and Gab2-/- mast cells.
Main Results:
- Gab2-/- mice exhibit normal health but show defective mast cell responses to FcεRI activation.
- Allergic reactions, including passive cutaneous and systemic anaphylaxis, are significantly impaired in Gab2-/- mice.
- FcεRI-dependent PI(3)K signaling pathways are defective in Gab2-/- mast cells, identifying Gab2 as the primary activator of PI(3)K in this context.
Conclusions:
- Gab2 is essential for FcεRI-mediated mast cell activation and allergic responses.
- Gab2 acts as the principal activator of PI(3)K downstream of FcεRI.
- Gab2 and its associated signaling molecules represent potential therapeutic targets for treating allergies.
Related Concept Videos
01:10Antibody Structure
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
02:06Allergic Reactions
Overview
01:22Activation 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...
01:09GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
01:31Immunoglobulin-like Cell Adhesion Molecules
Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
01:27Allergic Drug Reactions
Allergic reactions related to drugs are hypersensitivity responses driven by the immune system and bear no connection to the drug's therapeutic action. While drugs in isolation do not trigger an immune response, they can interact with endogenous proteins to form antigens. These antigens stimulate lymphocytes to produce antibodies. IgE-type antibodies attach themselves to mast cells. Upon subsequent exposure to the same stimulus, the antigen-antibody interaction is initiated, unleashing numerous...