Ask about this productRelated genes to: MAP2K4 antibody
- Gene:
- MAP2K4 NIH gene
- Name:
- mitogen-activated protein kinase kinase 4
- Previous symbol:
- SERK1
- Synonyms:
- MEK4, JNKK1, PRKMK4, MKK4
- Chromosome:
- 17p12
- Locus Type:
- gene with protein product
- Date approved:
- 1997-11-11
- Date modifiied:
- 2015-02-03
Related products to: MAP2K4 antibody
Related articles to: MAP2K4 antibody
- High-grade serous ovarian carcinoma (HGSC) is the sixth leading cause of cancer-related death among women. Most tumors arise from the Fallopian tubal epithelium (TE), exhibit numerous mutations, and present heterogenous pathological features. However, the contribution of specific mutation combinations to cellular transformation, pathological phenotype and chemotherapeutic responses remains unclear. We used a mouse TE organoid platform for combinatorial CRISPR mutagenesis of 20 candidate HGSC driver genes. Besides Trp53, mutations in Nf1, Cdkn2a and Map2k4 were the most prevalent in phenotypically transformed organoids. Map2k4 mutant organoids transplanted into mice predominantly yielded papillary-glandular carcinomas, whereas those with Nf1 mutations were more mesenchymal-like. Map2k4 mutant cells were particularly sensitive to paclitaxel, and Rho kinase inhibitor (ROCKi) increased trametinib sensitivity in both Map2k4- and Nf1-mutant organoids. This organoid mutagenesis strategy is powerful for unraveling the genetic and phenotypic complexity of HGSC, and identified Map2k4 as a potential therapeutic target in select HGSC cases. - Source: PubMed
Publication date: 2026/04/15
Phuong Daryl JRalston Coulter QEzzat Tony MAshe Christopher SArmstrong Amanda PFlesken-Nikitin AndreaYamulla Robert JNikitin Alexander YuSchimenti John C - Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment (TME) that contribute to tumor progression and therapeutic resistance in non-small cell lung cancer (NSCLC). However, effective strategies targeting CAF regulation remain limited. Here, we investigated the effects of the plant-derived compound 20(S)-Ginsenoside Rg3 on CAFs using an integrated network pharmacology and experimental validation approach. Network pharmacology analysis identified 107 overlapping targets between Rg3 and NSCLC. PPI network analysis highlighted EGFR, JUN, TP53, and STAT3 as key hub genes. KEGG enrichment analysis indicated that these targets were significantly enriched in the IL-17 and MAPK signaling pathways. These genes and pathways have been associated with fibroblast activation and tumor stromal remodeling, suggesting a potential role of Rg3 in regulating CAF-related processes within the tumor microenvironment. Functional experiments demonstrated that Rg3 inhibited CAF proliferation, colony formation and migration, while inducing apoptosis and mitochondrial dysfunction. Mechanistically, Rg3 upregulated IL-17RD and suppressed FGFR1-MAP2K4-JNK-c-Jun signaling. Furthermore, co-culture experiments revealed that Rg3-treated CAFs exhibited reduced pro-tumorigenic effects on NSCLC cells, indicating impaired tumor-stroma communication. Collectively, these findings demonstrate that 20(S)-Ginsenoside Rg3 suppresses CAF activation and function associated with the IL-17RD-FGF-MAP2K4-JNK-c-Jun signaling pathway, highlighting its potential as a tumor microenvironment-targeted therapeutic agent in NSCLC. - Source: PubMed
Publication date: 2026/04/06
Zhang XinyuXia LeiCheng FengZhuang JihongRao RuiyingMeng JiaqiXu JinheZhang WentingYu Zongyang - To evaluate targeted therapy for Langerhans cell histiocytosis (LCH) with maxillofacial manifestations, we conducted a retrospective study of 20 children admitted from January 2016 to June 2021. - Source: PubMed
Publication date: 2026/03/26
Jiang YangLi ZhigangYang YingZhang RuiWang TianyouYu Guoxia - Standardized salvage treatments for refractory/relapse Langerhans cell histiocytosis (LCH) remain to be established. Trametinib (TRA) has shown marked efficacy in LCH, but cohort studies regarding efficacy and safety of TRA monotherapy in refractory/relapse LCH were scarce. - Source: PubMed
Publication date: 2026/03/13
Wang WenqianFang ZishiGe JianZhao YunzeWang DongCui LeiZhou ChenxinLi ZhigangWang TianyouZhang Rui - The c-Jun N-terminal kinase (JNK) pathway is a central driver of fibrosis, inflammation, and neurodegeneration. While direct JNK inhibitors have shown therapeutic promise, achieving high isoform selectivity remains a significant medicinal chemistry challenge. Furthermore, targeting the upstream 'gatekeepers' MKK4 and MKK7 offers a distinct mechanism to modulate pathway output with greater precision. Consequently, medicinal chemistry efforts have shifted upstream to the dual-specificity kinases MKK4 and MKK7. This review critically evaluates the structural biology and pharmacological evolution of small-molecule inhibitors targeting these nodes. We contrast the distinct therapeutic landscapes of the two kinases: while MKK4 inhibition has emerged as a breakthrough strategy for unlocking liver regeneration (exemplified by the first-in-class clinical candidate HRX215), MKK7 inhibition is primarily pursued for its anti-fibrotic and anti-inflammatory potential. Special attention is given to structure-based design strategies, including the exploitation of the unique hinge-region cysteine (Cys218) for MKK7-specific covalent targeting and the optimization of scaffold selectivity against off-targets like BRAF. Finally, we discuss emerging modalities, such as PROTACs and dual inhibitors, outlining a roadmap for the next generation of precision therapeutics targeting the MKK-JNK axis. - Source: PubMed
Publication date: 2026/02/15
Zhao MinLi BaojianGao YingLiang YanShao NanqiShi XinboLi Jie