Phospho ZAP70 (Y493_Y494) Blocking Peptide
- Known as:
- Phospho ZAP70 (Y493_Y494) Blocking Peptide
- Catalog number:
- BP302-009P
- Product Quantity:
- 50 ug
- Category:
- Peptides
- Supplier:
- Beth
- Gene target:
- Phospho ZAP70 (Y493_Y494) Blocking Peptide
Related genes to: Phospho ZAP70 (Y493_Y494) Blocking Peptide
- Gene:
- ZAP70 NIH gene
- Name:
- zeta chain of T cell receptor associated protein kinase 70
- Previous symbol:
- SRK
- Synonyms:
- ZAP-70, STD
- Chromosome:
- 2q11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1995-05-16
- Date modifiied:
- 2019-04-23
Related products to: Phospho ZAP70 (Y493_Y494) Blocking Peptide
Related articles to: Phospho ZAP70 (Y493_Y494) Blocking Peptide
- Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by antibody-mediated platelet destruction and impaired regulatory T-cell (Treg) function, yet its molecular basis remains poorly defined. Here, we show that CD4+ naive T cells from patients with ITP exhibit diminished T-cell receptor (TCR) signaling and impaired in vitro Treg induction relative to healthy controls. RNA-sequencing revealed widespread alternative splicing dysregulation, most notably exon 8 skipping in LCK, a kinase central to TCR signaling and Treg differentiation. Using an LCK minigene combined with RNA pull-down mass spectrometry and RNA immunoprecipitation assays, we identified the splicing factor SRSF1 as a direct upstream regulator of LCK exon 8 skipping. Notably, SRSF1 expression was reduced in CD4+ naive T cells from ITP patients, and its overexpression restored in vitro Treg induction capacity. Antisense oligonucleotide (ASO)-mediated blockade of SRSF1 binding to LCK enhanced exon 8 skipping and attenuated TCR activation in Jurkat cells. Although murine Lck lacks the human-specific recursive splicing sites required for exon 8 exclusion, adoptive transfer of CD4+ naive T cells expressing the exon 8-skipped murine Lck into CD61-knockout mice significantly reduced Treg proportions and platelet counts in an active ITP model. Mechanistically, Jurkat cells engineered to express only the exon 8-skipped LCK variant showed markedly reduced binding to ZAP70 and CD3ζ, which may partly account for the attenuated TCR signaling and downstream FOXP3 induction. Together, these findings define a novel SRSF1-LCK splicing axis that may regulate Treg development in ITP. - Source: PubMed
Publication date: 2026/08/17
Hu XiangLeng ShaoqiuLiu YanZhao RuxiaLiu XinyueLi JuZhang ChengMeng CaiyunLiu HaoranZhang YanqiLi ChaoyangWang YuxinFeng QiJiang NanXu ShuqianWang ShuwenPeng Jun - T-cell receptor (TCR) signaling is essential for adaptive immunity in vertebrates, with the tyrosine kinases Fyn, Lck, and Zap-70 playing central roles in signal transduction. In the present study, the full cDNA sequences of Fyn, Lck, and Zap-70 from golden pompano (Trachinotus ovatus) were obtained by RT-PCR and RACE-PCR and their expression patterns in normal tissues and head kidney (HK) following lipopolysaccharide (LPS), polyinosinic-polycytidylic acid (polyI:C) stimulation and Vibrio alginolyticus infection were examined by qPCR. The open reading frames of trFyn, trLck, and trZap-70 respectively encoded 537, 513, and 609 amino acids, all containing conserved similar functional domains as their mammalian counterparts. qPCR analysis revealed that all three genes were ubiquitously expressed in examined tissues, with high expression in immune-related tissues. trFyn, trLck, and trZap-70 were significantly induced in HK after LPS, polyI:C stimulation and V. alginolyticus infection. Co-immunoprecipitation (co-IP) assay demonstrated that both trFyn and trLck could interact with trZap-70 in HEK-293T cells. These findings provide molecular basis for further study of the TCR signaling and T-cell mediated immunity in golden pompano. - Source: PubMed
Publication date: 2026/08/12
Wei YouchuanGan DongqiangQi WenruiXie YushuaiTian JingyunPan MingzhuQi Zhitao - This study examines sulfamethoxazole (SMX), a sulfonamide antibiotic strongly associated with severe cutaneous adverse effects, as a potential regulator of invariant natural killer T (iNKT) cells. This work combines molecular docking (to evaluate the likelihood of SMX binding to residues within a conventional binding pocket), molecular dynamics (to assess the stability of SMX binding and the forces that may destabilize the interaction), flow cytometry (to evaluate iNKT-cell activation in the presence of SMX within the context of established antigen presentation models), and particularly Raman spectroscopy (to investigate whether SMX-associated spectral features are retained after co-incubation and interaction) directly on sorted iNKT cells. Functional activation was assessed through IFN-γ production from sorted iNKT cells and correlated with Raman spectral data to support our hypothesis. The Raman spectroscopy was performed on both CD1d dimer (in isolation) as the presenter molecule of the drug and in sorted iNKT cells (in isolation), to identify spectroscopic evidence of drug-CD1dimer or drug-cell interactions under near-physiological conditions. From the CD1d experiment, we observed spectral features consistent with potential interactions between CD1d and serum-derived lipids, in a manner comparable to the positive control (α-GalCer). From the iNKT experiment, peaks at 1610 and 1663 cm-1 are the representative peaks that emerge under SMX stimulation conditions in iNKT cells (through TCR binding), as identified by second principal component (PC2) analysis. From the complete experiment, (CD1d + iNKT) suggests the possibility of a direct interaction between SMX and iNKT TCRs. Flow cytometry analysis further demonstrated a significant increase in ZAP-70 phosphorylation in sorted iNKT cells exposed to SMX under serum-free conditions, supporting the possibility of proximal TCR-associated signaling in the absence of CD1d. - Source: PubMed
Hernández-Jaimes O AZárate-Reyes J MLópez-Luis M AOrtiz-Sánchez EGallardo-Hernández S - TRAIL is a TNF family ligand that trimerizes TRAIL-R1 (DR4) or TRAIL-R2 (DR5) to induce apoptosis, necroptosis, and/or NF-κB activation in receptor-bearing cells. We previously identified TRAILshort as a splice variant of TRAIL that lacks cysteine 230, cannot trimerize, and acts as a dominant-negative ligand that blocks TRAIL-mediated apoptosis. TRAILshort is expressed on cell surfaces and within extracellular vesicles, enabling it to confer TRAIL resistance to both producing and bystander cells. In this study, we showed that elevated TRAILshort levels were associated with chronic viral infections, cancer, and autoimmune diseases, suggesting a link to impaired immune regulation. Using unbiased phosphoproteomics and mechanistic studies, we demonstrated that TRAILshort binding to DR5 recruited and activated the phosphatase Src homology region 2 domain-containing phosphatase 1 (SHP-1), leading to zeta-chain-associated protein kinase 70 (ZAP-70) dephosphorylation, disruption of ZAP-70-CD3ζ interactions, and impaired T cell receptor signaling, thereby reducing T cell activation, proliferation, and cytokine production in response to antigen or CD3/CD28 ligation. Genetic or pharmacologic SHP-1 inhibition reverses these effects. In humanized mouse models, TRAILshort promoted the persistence of transformed mouse embryonic fibroblasts (MEFs) and L428 and antagonized CD19-directed CAR T cell activity, revealing TRAILshort as an immunomodulator of T cell function with therapeutic implications, including blocking TRAILshort to restore T cell immunity or delivering TRAILshort to enforce tolerance. - Source: PubMed
Publication date: 2026/08/03
Jalali ShahrzadNatesampillai SekarNie ZilinZhang YingCan IsmailChandrasekar Aswath PHameister Brianna MCorreia CristinaZhao Tuantuan VMun Dong-GiGarcia-Rivera EnriqueMatson RobertKrogman AshtonMaynes Mark ABatchelor RobinMonie Dileep DLi HuBehfar AttaKenderian Saad SPandey AkhileshAnsell Stephen MTaner TimucinWeyand CorneliaBilladeau Daniel DBadley Andrew D - Cytotoxic T lymphocytes (CTLs) play a pivotal role in antitumor immunity via inducing apoptosis in cancer cells. However, their effector functions can be compromised by the perturbations in the tumor microenvironment (TME). Among the diverse factors within the TME, the effects of stiffness of the extracellular matrix (ECM) on CTL-mediated responses require greater understanding. To address this gap, we three-dimensionally bioprinted CTLs and targeted cells in polyethylene glycol-based ECM mimics with tunable stiffness and uniform porosity. Our findings reveal that CTLs in stiffer ECMs showed reduced migration speed and impaired antigen-specific cytotoxicity. Synapse formation analysis revealed that stiffer ECMs impair CTL efficacy not by reducing the frequency of CTL-target cell contacts but by shortening the contact time between these cells, a consequence of disrupted immunological synapse formation. Live Ca imaging and expression of phospho-ZAP70 confirmed these findings. Together, these results suggest that ECM stiffness modulates CTL function at multiple levels, from migration to cytotoxicity and synapse quality. - Source: PubMed
Publication date: 2026/07/31
Seyedzadeh Mir HadiTolentino MA KristineGil Peres NewtonDu Eric YBartlett-Tomasetig FlorenceJavier Gaia M NKilian Kristopher AGaus KatharinaGoyette JesseGooding J Justin