Ask about this productRelated genes to: PRAK antibody
- Gene:
- MAPKAPK5 NIH gene
- Name:
- MAPK activated protein kinase 5
- Previous symbol:
- -
- Synonyms:
- PRAK
- Chromosome:
- 12q24.12-q24.13
- Locus Type:
- gene with protein product
- Date approved:
- 1999-03-26
- Date modifiied:
- 2019-04-12
Related products to: PRAK antibody
Related articles to: PRAK antibody
- AMP-activated protein kinase (AMPK) serves as a crucial energy sensor, maintaining organismal energy homeostasis through the regulation of diverse metabolic pathways. However, the association between the AMPK signaling pathway and hypoxia adaptation in yak lung tissue has not yet been elucidated. Consequently, this study focused on the lung tissues of yaks and cattle residing at the same altitude (2600 m). Morphological analysis demonstrated that, compared to cattle, yak lung tissue possessed significantly thicker alveolar septa (P < 0.05), a greater abundance of elastic fibers (P < 0.05), and a reduced blood-air barrier thickness (P < 0.05), suggesting substantial structural adaptations in the yak lung under identical altitudinal conditions. RNA-seq analysis identified 3684 genes with significant differential expression between yaks and cattle. KEGG pathway enrichment analysis showed significant enrichment for the AMPK signaling pathway under the "Environmental Information Processing" category, and Gene Set Enrichment Analysis (GSEA) further confirmed the activation of the AMPK signaling pathway in yak lung tissue. Despite qRT-PCR indicating reduced mRNA levels of key AMPK pathway genes (PRKAA1, PRKAA2, PRKAB1, PRKAG2) in yak lung tissue, Western blot analysis demonstrated a marked upregulation in the relative abundance of phosphorylated AMPK (P-AMPK α1 + α2), implying potential activation of the AMPK signaling pathway via phosphorylation in yak lung tissue. Further analysis of downstream gene expression within the AMPK signaling pathway indicated significant downregulation of genes associated with glucose metabolism (PCK2, G6PC1), lipid metabolism (FASN, ACACA), protein metabolism (MAPKAPK5, MTOR), cell proliferation and apoptosis (RPTOR, MTOR), and autophagy (TXNIP, NLRP3) in yak lung tissue. These findings suggest that, relative to cattle, the yak lung may adapt to hypoxic conditions by minimizing energy expenditure, suppressing aberrant cell proliferation, mitigating oxidative stress, and reducing inflammatory responses. In summary, the activation of the AMPK signaling pathway in yak lung tissue may play a crucial role in hypoxic adaptation by enhancing oxygen utilization and energy supply capacity. - Source: PubMed
Publication date: 2026/04/04
Zhang XunDing WeiqinWang HuizhenLi JingyiChen JiaruiWei Qing - Alternative splicing plays a crucial role in the development and progression of hepatocellular carcinoma (HCC), yet the underlying regulatory mechanisms and therapeutic potential remain largely unexplored. Here, we identified the RNA-binding protein FMR1 autosomal homolog 1 (FXR1) as a key driver of HCC pathogenesis through the regulation of alternative splicing. FXR1 was highly expressed in HCC tissues, and its elevated expression was associated with a poor prognosis. Mechanistically, high FXR1 induced the retention of exon 6 in mitogen-activated protein kinase-activated protein kinase 5 (MK5), generating a long, kinase-competent isoform (termed MK5-L). This isoform acted as an important oncogenic factor for HCC progression by phosphorylating GSK3β and subsequently activating the Wnt/β-catenin pathway. Functional studies showed that the FXR1/MK5-L axis is critical for HCC cell proliferation and metastasis, both in vivo and in vitro. Importantly, therapeutic intervention using an FXR1-targeting antisense oligonucleotide (ASO) effectively suppresses tumor progression and metastasis in preclinical models by shifting splicing toward the inactive MK5-S isoform. Overall, our study unveils a novel splicing-mediated oncogenic pathway and establishes FXR1 and its downstream target MK5-L as promising prognostic biomarkers and therapeutic targets for HCC. - Source: PubMed
Publication date: 2026/04/09
Li YutongXiang JinCheng BinLi ChenhaoWang KaiTang NiHuang Luyi - Skeletal muscle plays a central role in whole-body energy expenditure and metabolic homeostasis, and improving its mitochondrial function and oxidative fiber profile is considered an effective strategy to counteract diet-induced metabolic impairments, although the molecular regulators of these adaptations are not yet fully understood. Erk3 has been implicated in myotube differentiation and in skeletal muscle adaptations to aerobic exercise; however, its potential role in skeletal muscle during diet-induced metabolic dysfunction remains to be determined. - Source: PubMed
Publication date: 2026/02/24
Loza-Valdes AngelAcosta-Gallo CarlosKassouf TouficBelykh AndreiStelmach MałgorzataMalińska DominikaEl Ghoz KatiaEl-Merahbi RabihDziaczkowski FilipKolczyńska-Matysiak KatarzynaSumara Grzegorz - Multiple p38 MAP kinase inhibitors have been developed for the treatment of inflammatory diseases such as rheumatoid arthritis, but their effectiveness has been limited due to toxicity and tachyphylaxis, leading to a lack of clinical benefit. Efforts have been made to circumvent this limitation by targeting individual substrates downstream of p38, including MK2 and MK5. This approach has failed to yield clinical benefit despite preclinical evidence of a therapeutic effect. We hypothesized that there is redundancy in the MAPK activating kinase family that would necessitate blocking multiple kinases to sufficiently impact inflammatory processes. We used heterobifunctional protein degraders that either specifically degraded MK2 selectively or degraded MK2/3/5 simultaneously to test the hypothesis, in addition to genetic approaches to enable knockdown. In human PBMCs, elimination of MK2/3/5 with heterobifunctional degraders resulted in full reduction of TLR4 or TLR7/8 induced TNFα, whereas MK2-specific degradation only attenuated TNFα biosynthesis. In contrast, both specific MK2 degradation and broad MK2/3/5 degradation inhibited TGF-β-induced collagen production in human fibroblasts. This observation was consistent with genetic deletions of MK2, MK3 and MK5 (singly and in combination) whereby single deletion of MK2, MK3 or MK5 attenuated lipopolysaccharide (LPS) induced TNFα production and had no effect on R848-induced TNFα production. Double deletion of MK2 and MK3 or MK2 and MK5 or MK2/3/5 triple deletion had a significantly greater effect on TNFα production regardless of stimulus. The combined data suggest cooperativity between MK2 and either MK3 or MK5 for efficient, cell context-dependent modulation of inflammatory responses. - Source: PubMed
Publication date: 2026/01/14
Yang BinFang GuoqiangMarx IsaacLiu GuangSkouras StephanieSharma KirtiWalther Dirk MBollinger Martinez SarahHubeau CedricShi YataoDe Savi ChrisHuang XinHuhn AnnissaSawant RupaProctor William RDixit Vaishali SDong HuijunWeiss Matthew MMainolfi NelloSlavin AnthonyLong Andrew JWilliams Juliet AByrne Fergus R - Chronic cadmium exposure is linked to esophageal squamous cell carcinoma (ESCC) progression, treatment resistance, and poor prognosis, but its molecular mechanisms remain unclear. Based on whole-transcriptome sequencing (RNA-seq) on chronic cadmium-treated (CCT) and untreated human EC109 ESCC cells, we performed lncRNA-mRNA co-expression and protein-protein interaction (PPI) network analyses to screen the hub genes related to cadmium exposure. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses depicted that these genes were mainly enriched in nucleocytoplasmic transport, ferroptosis, Huntington disease, and cellular senescence. Based on the lncRNA-miRNA-mRNA potential interaction, three lncRNAs (AC107068.1, TTN-AS1, MAPKAPK5-AS1) and ten mRNAs (IPO5, NUDCD1, OSTM1, CCNB1, FANCD2, TFRC, POLR2B, HTT, NUP43, NBN) were selected for competitive endogenous RNA (ceRNA) network construction. Connectivity map (CMap) analysis for the target mRNAs showed that JAK3-inhibitor-I was the most promising therapeutic drug for cadmium-induced ESCC progression. The prognostic value and abnormal expression of the candidate mRNAs were then validated in TCGA cohorts, cadmium-treated cancer cells and 41 ESCC specimens. Moreover, migration and invasion assays were performed to assess the effects of the identified gene on cell malignant phenotypes. As a result, IPO5 was identified as the pivotal gene and MAPKAPK5-AS1-hsa-miR-379-5p-IPO5 was deemed as a potential ceRNA regulatory mechanism for cadmium carcinogenesis in ESCC. Using TIMER and EPIC algorithms, IPO5 was correlated with increased infiltration of CD4 T cells and macrophages, while negatively associated with CD8 T cells and NK cells in ESCC tissues. Collectively, our study provides valuable information in understanding the molecular mechanisms involved in cadmium-induced ESCC progression and treatment resistance. Furthermore, we predict potential agents for cadmium carcinogenicity prevention and treatment. - Source: PubMed
Publication date: 2025/12/25
Zhu RuiChen JiongyuZhang XiarongChen QianJin YingmingZeng MingqinLuo JiananHuang YitengPeng Lin