Ask about this productRelated genes to: ZAP70 protein
- 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: ZAP70 protein
Related articles to: ZAP70 protein
- Pulmonary fibrosis (PF) is a life-threatening interstitial lung disease characterized by scarring and inflammation in lung tissues. Aberrant activation of the JAK/STAT and NF-κB signaling pathways is critical in initiating and sustaining the inflammatory processes that drive fibrotic progression. In this study, we identify a novel small-molecule compound, T4015, a 4-indolyl-2-phenylaminopyrimidine derivative, as a dual-pathway inhibitor targeting both JAK/STAT and NF-κB signaling. Dual-luciferase reporter assays demonstrate the potent inhibitory activity of T4015 against these pathways. T4015 effectively suppresses the phosphorylation of STAT3, JAK1, and TYK2 induced by IL-6 and IFN-β, while suppressing LPS-induced NF-κB activation in macrophages. Transcriptome sequencing and pathway enrichment analyses further confirm that T4015 downregulates multiple inflammation-related signaling cascades, including the JAK/STAT, NF-κB, TNF, IL-17, and Toll-like receptor pathways. In a mouse model of bleomycin-induced PF, T4015 treatment significantly improves survival, attenuates collagen deposition, and reduces the expression of pro-inflammatory and profibrotic markers such as IL-6, CCL2, and COL1. Molecular docking and target prediction analyses suggest that T4015 exhibits strong binding affinity for multiple kinases within the JAK/STAT and NF-κB networks, including JAK1, TYK2, JAK2, JAK3, RIPK1, IRAK1/4, TAB1, and ZAP70. Collectively, these results highlight T4015 as a promising therapeutic candidate for PF through its simultaneous inhibition of the JAK/STAT and NF-κB signaling pathways. - Source: PubMed
Publication date: 2026/04/25
Zhang MinghuiXu HangLiu ShanXu XiaohanYin JiayiZhang XinxinZhang XiaonanYang XiaopingLiu XiaochunYin BinZhou MingmingWang LeweiZhang MengLiu HuiyingJiang WenqingSong QiaolingYang Jinbo - Actin-rich protrusions densely cover the surface of T cells and are well characterised for their role in migration. Recent studies have uncovered their contribution to antigen surveillance and immune signalling. To further explore how protrusions initiate signalling pathways mediating T-cell activation, we performed live-cell imaging of endogenously tagged proteins in HER2-specific chimeric antigen receptor (CAR) T cells targeting HER2⁺ breast-cancer cells. Quantitative STED microscopy allowed us to monitor protein rearrangement and to correlate it with membrane topology over time. Before activation, key signalling proteins (including Lck, CD45, LAT, and the CAR) were not enriched in protrusions. Upon contact with target cells, rapid protein reorganisation occurred preferentially within protrusions, initiating signalling. HER2-CAR clustering, accompanied by ZAP-70 and LAT recruitment, was enhanced in protrusions. While Lck distribution remained unchanged, exclusion of the phosphatase CD45 was enhanced at protrusion-cell contacts, independently of the CAR signalling domain. Overall, signalling machinery rearranged faster and more effectively at protrusive contacts than at main plasma membrane regions. Together, our data re-frame protrusions as sites of enhanced receptor activation by exclusion and clustering dynamics rather than by pre-enrichment of the signalling machinery. - Source: PubMed
Publication date: 2026/04/21
Rodilla-Ramirez CarmenCarai GiorgiaFox EleanorZehtabian AminAdam HelenDallio KatjaLazki-Hagenbach PiaEwers HelgeSu XiaoleiBottanelli Francesca - Gastric cancer (GC) remains one of the most prevalent and lethal malignancies worldwide. Natural flavonoids are increasingly recognized for their therapeutic potential due to their multi-target actions and favourable safety profiles. Morin, a dietary flavonol found in several plants of the Rosaceae, Moraceae, and Fagaceae families, has not been well explored in GC. In this study, network pharmacology analysis identified ten major morin-associated hub genes (PIK3R3, PIK3CA, PIK3CB, PIK3CD, PIK3R2, PLCG1, JAK2, IGF1R, ZAP70, and ERBB4), several of which are key regulators of the PI3K-Akt signalling axis. Molecular docking showed strong binding affinities of morin toward PIK3CD (-11.01 kcal/mol), ZAP70 (-10.72 kcal/mol), JAK2 (-10.53 kcal/mol), IGF1R (-9.99 kcal/mol), PIK3CA (-9.79 kcal/mol), and ERBB4 (-8.83 kcal/mol). Molecular dynamics simulations of 500 ns, along with PCA, DCCM, FEL, and MM-GBSA analyses further confirmed stable interaction of morin with PIK3CA. In vitro, morin demonstrated selective cytotoxicity, with low IC values in AGS (15.16 ± 0.02 μM) and NCI-N87 (15.85 ± 0.8 μM) GC cells, compared to a significantly higher IC in normal MCF10A cells (101.97 ± 2.61 μM). Wound-healing assays showed that morin inhibits AGS cell migration in a dose- and time-dependent manner. Integrating in silico and in vitro evidence, we propose that morin primarily targets PIK3CA leading to modulation of the PI3K-Akt pathway, thereby contributing to reduced proliferation and migration of GC cells. Together, these findings highlight morin as a promising natural molecule with therapeutic potential against gastric cancer. - Source: PubMed
Publication date: 2026/04/10
Naskar NileshKumar SunilMamgai DeepanshuVishwakarma Harish ChandraKumar Guru SantoshMathew BijoMaliyakkal NaseerKumar Uday RShrivastava ShwetaJeengar Manish Kumar - Rheumatoid arthritis (RA) is a chronic autoimmune disease that drives progressive joint destruction and functional disability. Current therapies are often limited by inadequate efficacy and risks of broad immunosuppression. Immunoglobulin D (IgD) is a conserved antibody isotype with poorly understood functions. We previously reported aberrant IgD secretion in RA and its capacity to activate T cells, yet the putative IgD receptor (FcδR) remained unidentified. - Source: PubMed
Publication date: 2026/04/06
Hu XiaoxiHan ChenchenHuang DongliangXu JingHe JingjingWu TiantianDong ManlingZhao JieminLi TaoWu YujingWei Wei - This study aimed to identify key molecular signatures and therapeutic targets in early sepsis through integrated bioinformatics analysis. - Source: PubMed
Publication date: 2026/03/23
Gai XiaoweiLi YaqingWang YananGao DanWu ShanshanGeng YananZhang JiaminYao MinghuiYao GaiqiWang Qiuyan