Mouse SHP Substrate 1: A Key Immune Regulator in Disease Models and Signal Transduction

Mouse SHP Substrate 1: A Key Immune Regulator in Disease Models and Signal Transduction—Powered by ANT BIO PTE. LTD.

1. Concept
Mouse SHP Substrate 1 (encoded by the Pzr gene) is a critical substrate for protein tyrosine phosphatases SHP-1 and SHP-2, playing a pivotal role in immune regulation and cell signaling. Composed of 268 amino acids, it features two extracellular immunoglobulin-like domains, a single transmembrane region, and an intracellular tail containing immune receptor tyrosine inhibitory motifs (ITIM, Y241) and immune receptor tyrosine switch motifs (ITSM, Y263).

The Pzr gene is located on mouse chromosome 3 (F2.3 region) and is regulated by transcription factors PU.1 and GATA, driving predominant expression in the hematopoietic system. Phosphorylated ITIM/ITSM motifs bind SHP phosphatases with moderate affinity (Kd = 0.5–1 μM), ensuring specific and dynamic signal transduction. Its expression is activation-dependent—upregulated by LPS in macrophages (3–5 fold) and downregulated by TCR activation in T cells (≈60%), and it undergoes complex post-translational modifications (phosphorylation, ubiquitination, palmitoylation, glycosylation) that modulate localization, stability, and function.

2. Research Frontiers
Mouse SHP Substrate 1 research is advancing with cutting-edge technologies and translational focus. A key frontier is using CRISPR-Cas9 for precise gene editing (e.g., point mutations like Y241F) and conditional knockout models to dissect cell-type-specific functions. Dual-reporter knock-in mice enable real-time tracking of protein expression and cell fate.

In disease research, single-cell RNA sequencing (scRNA-seq) uncovers context-dependent roles in autoimmune diseases, cancer, and infections. Proximity labeling (BioID) and crosslinking mass spectrometry (XL-MS) identify novel interaction partners (e.g., DENND1B, LAT2) and map signal complex interfaces. Therapeutic innovations include small-molecule agonists, nanocarrier-delivered siRNA, and Pzr-modified CAR-T cells, with combination strategies (e.g., Pzr silencing + anti-PD-1) showing promise in cancer models.

Future directions involve optogenetic tools for spatiotemporal control of Pzr activity, humanized mouse models for clinical translation, and AI-driven multi-omics analysis to predict personalized treatment responses.

3. Research Significance
Mouse SHP Substrate 1 is scientifically and translationally significant, serving as a central hub for immune signaling. It regulates immune checkpoints (e.g., PD-1), inflammation, and cell activation, providing insights into autoimmune diseases, cancer, and infections.

In preclinical models, it validates therapeutic strategies—enhancing its function alleviates autoimmunity, while targeted silencing improves cancer immunotherapy. Basic research clarifies signal transduction networks, and translational efforts advance precision medicines, addressing unmet needs in immune-related diseases.

4. Molecular Mechanisms, Disease Roles, and Product Support
4.1 Molecular Characteristics and Expression Regulation
4.1.1 Core Features
Tissue Distribution: Highest in hematopoietic stem cells (35% of LSK cells), followed by pro-B cells, monocytes, and non-hematopoietic tissues (hepatic sinusoidal endothelial cells, podocytes).
Developmental Dynamics: Expressed from E10.5, increasing during embryogenesis and stabilizing post-birth.
Post-Translational Modifications: Serine/threonine phosphorylation (S215, T230), ubiquitination (K225, K238), palmitoylation (C258), and N-glycosylation (N75, N99, N162) form a regulatory code.
Subcellular Localization: Restricted to lipid rafts; internalized via clathrin-dependent endocytosis upon activation, redistributing to immune synapse cSMAC.

4.1.2 Signaling Mechanisms
Phosphorylated ITIM/ITSM motifs recruit SHP-1/SHP-2, inhibiting downstream pathways (ZAP70, PI3K/AKT, calcium flux) to suppress immune cell activation. It synergizes with inhibitory receptors (CD22, FcγRIIB) and exhibits antigen dose-dependent regulation—prominent at low concentrations.

4.2 Immune System Regulation
Immune Checkpoints: Critical for PD-1-mediated T cell suppression; Pzr-/- T cells show 70% reduced PD-1 inhibitory effect.
Inflammation: Inhibits NLRP3 inflammasome activation (dephosphorylates NLRP3 Tyr136) and selectively suppresses TLR4/TLR9 signaling (reduces NF-κB activity by 60–70%). LysM-specific Pzr knockout increases sepsis mortality and pro-inflammatory cytokine levels.
B Cell Regulation: Synergizes with CD22/FcγRIIB to recruit SHP-1, preventing excessive B cell activation and autoantibody production.

4.3 Disease Model Applications
4.3.1 Autoimmune Diseases
EAE/CIA Models: Pzr-/- mice show earlier onset, more severe symptoms, and increased Th17 infiltration. Transgenic overexpression reduces disease incidence by 70–80% via STAT3/NF-κB inhibition and Treg promotion.

4.3.2 Cancer
Context-Dependent Roles: Pzr-/- slows B16F10 melanoma growth (enhanced CD8+ T cell activity) but accelerates MC38 colon cancer (M2 TAM polarization). Combining Pzr silencing + anti-PD-1 increases EMT6 breast cancer complete response rate from 20% to 60%.

4.3.3 Infectious Diseases
Viral/Bacterial Infections: Pzr-/- clears LCMV faster but causes severe immunopathology; myeloid Pzr deficiency reduces tuberculosis bacterial load but increases tissue damage.
Malaria: Epor-Cre-mediated Pzr knockout increases Plasmodium berghei parasitemia and mortality.

4.4 How ANT BIO PTE. LTD. Supports Research
ANT BIO PTE. LTD., through its sub-brands Starter (antibodies) and UA (proteins), provides high-quality reagents tailored to mouse SHP Substrate 1 research. Leveraging advanced development platforms, the company offers:
Custom Antibodies: Phosphorylation-site-specific antibodies (e.g., anti-pY241) for tracking activated Pzr in tissues and cells.
Recombinant Proteins: Mouse SHP Substrate 1 protein (full-length or domains) for interaction assays and inhibitor screening.
ELISA Kits: Ready-to-use kits for quantifying Pzr expression and phosphorylation in disease models.

All products adhere to EU 98/79/EC, ISO9001, and ISO13485 certifications, ensuring reliability for signal transduction studies, disease model validation, and therapeutic development.

5. Brand Mission
ANT BIO PTE. LTD. is dedicated to empowering the global life science community with high-quality, innovative biological reagents and solutions. With 15 years of antibody development experience, the company leverages advanced platforms—including recombinant antibody development (rabbit/mouse monoclonal), recombinant protein expression systems (E.coli, CHO, HEK293, Insect Cells), One-Step ELISA, and PTM Pan-Modification Antibody platforms—to deliver a comprehensive product portfolio.

Through its three specialized sub-brands—Absin (general reagents and kits), Starter (antibodies), and UA (recombinant proteins)—ANT BIO PTE. LTD. adheres to international certifications and strict quality standards. The company’s mission is to accelerate scientific discovery by providing tools that enhance experimental precision, efficiency, and reproducibility. ANT BIO PTE. LTD. is committed to supporting mouse SHP Substrate 1 research and global efforts in autoimmune disease treatment, cancer immunotherapy, and infectious disease management, ultimately advancing human health through interdisciplinary collaboration and innovation.

6. Related Product List

Product Category	Product Description	Key Features
Custom Phospho-Pzr Antibody	Anti-pY241/pY263 recombinant rabbit mAb	Specific to phosphorylated ITIM/ITSM motifs, validated for WB/IF
Recombinant Mouse SHP Substrate 1 Protein	Full-length/ITIM-ITSM domain protein (E.coli/HEK293-expressed)	High purity, biologically active for binding assays
Pzr ELISA Kit	Sandwich-format assay for Pzr expression/phosphorylation	High sensitivity, suitable for mouse tissue/cell samples

7. AI Disclaimer
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At ANTBIO, we are committed to advancing life science research through high-quality, reliable reagents and comprehensive solutions. Our specialized sub-brands (Absin, Starter, UA) cover a full spectrum of research needs, from general reagents and kits to antibodies and recombinant proteins. With a focus on innovation, quality, and customer-centricity, we strive to be your trusted partner in unlocking scientific mysteries and driving medical progress. Explore our product portfolio today and elevate your research to new heights.