Related Experiment Video
Updated: Jun 12, 2026
08:45
Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
Published on: July 17, 2020
The adaptor protein Sh2d3c is critical for marginal zone B cell development and function
Amin Al-Shami1, Carrie Wilkins, Jeannette Crisostomo
1Lexicon Pharmaceuticals, The Woodlands, TX 77381, USA. aalshami@lexpharma.com
Journal of Immunology (Baltimore, Md. : 1950)
|May 28, 2010
Summary
Sh2d3c adaptor protein is crucial for marginal zone B cell development and function. Mice lacking Sh2d3c show impaired B cell responses, highlighting its role in immunity.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Sh2d3c is an adaptor protein involved in T cell activation and integrin signaling.
- The in vivo role of Sh2d3c in immune response and hematopoietic development is unclear.
Purpose of the Study:
- To investigate the in vivo function of Sh2d3c in immune regulation and hematopoietic cell development.
- To determine the specific role of Sh2d3c in T cell and B cell biology.
Main Methods:
- Generation and analysis of Sh2d3c-deficient mice (Sh2d3c(-/-)).
- Assessment of T cell and B cell populations, maturation, and function in vivo and in vitro.
- Evaluation of humoral immune responses against different antigen types.
Main Results:
- Sh2d3c deficiency primarily impacts marginal zone B (MZB) cell development and function.
- Sh2d3c(-/-) mice exhibit reduced MZB cell numbers and impaired antigen capture.
- B cell proliferation, cytokine production, and migration are reduced in Sh2d3c(-/-) cells, while T cell development and function remain largely normal.
Conclusions:
- Sh2d3c is essential for proper development and function of marginal zone B cells in vivo.
- Sh2d3c plays a critical role in humoral immune responses against thymus-independent antigens.
- The study underscores the specific in vivo importance of Sh2d3c in regulating B cell immunity.
More Related Videos
Related Concept Videos
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:20The 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...
01:30Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
00:50Anaphase Promoting Complex
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
01:15Receptor Downregulation in MVBs
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...