Ask about this productRelated genes to: TNK1 antibody
- Gene:
- TNK1 NIH gene
- Name:
- tyrosine kinase non receptor 1
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 17p13.1
- Locus Type:
- gene with protein product
- Date approved:
- 1998-12-03
- Date modifiied:
- 2018-07-17
Related products to: TNK1 antibody
Related articles to: TNK1 antibody
- The intestine is both a driver and a target of posttraumatic organ dysfunction. However, it remains unclear whether, and to what extent an extra-abdominal trauma, such as thoracic trauma with transient hemorrhagic shock and hind-limb ischemia (THS), provokes remote intestinal alterations. - Source: PubMed
Publication date: 2026/09/18
Meisen SophieDoerfer LenaMannes MarcoPalmer AnnetteHildebrand FrankKleger AlexanderHalbgebauer RebeccaHuber-Lang Markus - Deregulated inflammatory signaling via STAT family transcription factors, particularly STAT1, underlies a variety of immune-related diseases, including inflammatory bowel disease. Whereas activation of STATs by JAKs via canonical receptor-driven JAK-STAT signaling is well understood, little is known about JAK-independent mechanisms of STAT activation. Here, we identify the understudied nonreceptor tyrosine kinase TNK1 as a therapeutically targetable, JAK-independent activator of STAT signaling. Using a multiomics approach, we mapped a network of TNK1 substrates associated with protein condensates and proinflammatory signaling, including STAT1. We found that TNK1, but not its sister kinase ACK1, directly phosphorylates STATs at well described STAT-activating JAK sites. In cells, TNK1-mediated STAT1 phosphorylation and activation occurs independently of JAKs. Imaging and interactomics data suggest that TNK1 interacts with STAT1 in cytosolic condensates, which likely compartmentalize TNK1-substrate interactions. We show that an intrinsically disordered proline-rich region in TNK1, which includes a 14-3-3 docking phosphorylation site, is required for the formation of kinase-active TNK1 condensates and STAT1 phosphorylation. Mutations within the proline-rich region that eliminate 14-3-3 binding increase formation of TNK1 condensates, suggesting a model in which 14-3-3 acts as a clamp that constrains the flexible PRR to inhibit condensate formation and STAT1 activation. Finally, we show that TNK1 is a targetable driver of STAT1-mediated inflammation in the gut as inhibition of TNK1 reduces active STAT1 in the colon and ameliorates colitis symptoms in mice. - Source: PubMed
Publication date: 2026/08/26
López-Palacios Tania PMadhusanka DeshanScott Samuel MVaughan Alec JEgbert Christina MChan Tsz-YinBustos YaphetAshworth Spencer WTruman Jacob MPer Moreno AngelaTsang Tsz-MingJayatunge Dasun NYang JingshuNelson PaigeAl-Sudani FatimaTarara MadelynKohler EmmaleePereira Mendiola Nelson ESoderblom Erik JStubben Chris JStewart Paul AKolasangiani RezaDobish Kasidy KKnobel BeateBuckley Shannon MBidone Tamara CSmoot Rory LUchida Amiko MMorawe MareenArmacki MilenaAndersen Joshua L - The activated Cdc42-associated kinase (ACK) family, comprising TNK1 and ACK1/TNK2, are critical regulators of oncogenic signaling and epigenetic reprogramming. Their unique structural architecture, including ubiquitin-association domain, sterile alpha motif domain, and Mig6 homology regions, distinguishes them from other non-receptor kinases. ACK1 often, elevated in diverse malignancies, functions as a cytoplasmic transducer and nuclear epigenetic modifier, phosphorylating histones H4 at Tyr88 and H3 at Tyr54 driving cell survival, therapy resistance, and immune evasion. Conversely, TNK1 predominantly operates via ubiquitin‑mediated signaling, P activation, and STAT-dependent pathways in hematological cancers. Hence, understanding these mechanisms is crucial for developing targeted therapeutic strategies. - Source: PubMed
Publication date: 2026/07/28
Mittal RadhikaPriya PriyaBanerjee JyotirmoyDixit Aparna Banerjee - Lung cancer is a leading cause of cancer-related mortality, with current therapies limited by drug resistance and immunosuppressive tumor microenvironment (TME). Cuproptosis offers new therapeutic prospects, but effective induction and targeted delivery remain challenging. Herein, we developed xanthohumol (XN)-coordinated copper oxide/hyaluronic acid (XN@CuO/HA) nanobipyramids as a novel cuproptosis inducer for non-small cell lung cancer (NSCLC) therapy. XN@CuO/HA exhibited good colloidal stability, and potent antitumor activity by inducing mitochondrial dysfunction, reactive oxygen species (ROS) accumulation, and cuproptosis. Mechanistically, transcriptomic and functional analyses identified the FOXO1-GADD45G axis as a critical mediator of XN@CuO/HA-induced cuproptosis. , XN@CuO/HA significantly suppressed LLC xenograft growth in C57BL/6 mice with excellent biosafety. Moreover, it remodeled the immunosuppressive TME by enhancing CD8 T/NK1.1 cell infiltration and reducing MDSCs, synergizing with anti-PD-1 antibody to achieve superior antitumor efficacy. Collectively, our findings highlight XN@CuO/HA as a safe and effective nano-therapeutic that induces FOXO1-GADD45G-mediated cuproptosis and potentiates immunotherapy, providing a promising combinatorial strategy for NSCLC treatment. - Source: PubMed
Publication date: 2026/02/25
Jiang RuiyangHuang XiangmingOuyang YiranLuo BichongWan HongYangShou FangyangWu XiahuiFan JuntingZhang JingyuanSun DongdongXu ChangliangFang Zhijun - Fibrosis is a major challenge in glaucoma management, particularly following surgical interventions like trabeculectomy. In this study, we explored the therapeutic potential of a fibrosis-modulating peptide (VRF2019) and its mitomycin conjugate by evaluating their transcriptomic impact on primary Tenon fibroblast cells isolated from post-trabeculectomy tissues. To the best of our knowledge, this is the first comprehensive transcriptomic mapping of glaucoma-associated fibrotic fibroblasts, incorporating targeted drug delivery mechanisms. Fibroblasts were subjected to three conditions: Control (untreated), peptide treatment, conjugate treatment, and gene expression changes were analyzed through pairwise comparisons. Peptide-treated cells exhibited dysregulation in 231 transcripts, whereas conjugate-treated cells demonstrated more pronounced changes with 553 dysregulated transcripts. Comparisons between peptide- and conjugate-treated cells revealed 267 differentially expressed transcripts. Bioinformatic analysis highlighted key pathways affected by the treatments, including upregulation of IL-17, TNF-alpha, NF-kappa B, and Hippo signaling pathways, as well as suppression of protein phosphorylation and cell communication pathways. Kinase profiling revealed distinct and overlapping dysregulations across the conditions, with TGFBR1, EPHA2, and NUAK2 upregulated in peptide-treated cells, while conjugate treatment downregulated kinases such as PIM1, RET, and CAMKK1. Weighted gene coexpression network analysis identified significant hub genes, including TGFBR1 in the peptide-treated cells and TNK1 in conjugate-treated cells, elucidating key molecular players in fibrosis modulation. These findings demonstrate that the peptide and its conjugate exert significant antifibrotic effects by modulating transcriptional, signaling, and apoptotic pathways. The conjugate exhibited enhanced regulation of extracellular signaling and fibrotic pathways, suggesting its superior therapeutic potential. This study provides a foundational transcriptomic framework for advancing targeted therapies in glaucoma-associated fibrosis. - Source: PubMed
Publication date: 2025/09/26
Suresh Babu JayavigneeswariGaikwad Kiran BharatArumugam PavithraSharma JyotiElchuri Sailaja VGeorge RonnieJanakiraman Narayanan