MAP4K5 antibody - middle region (ARP33101_P050)
- Known as:
- MAP4K5 (anti-) - middle region (ARP33101_P050)
- Catalog number:
- arp33101_p050
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Aviva Systems Biology
- Gene target:
- MAP4K5 antibody - middle region (ARP33101_P050)
Related genes to: MAP4K5 antibody - middle region (ARP33101_P050)
- Gene:
- MAP4K5 NIH gene
- Name:
- mitogen-activated protein kinase kinase kinase kinase 5
- Previous symbol:
- -
- Synonyms:
- KHS1, GCKR, KHS
- Chromosome:
- 14q22.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-09-07
- Date modifiied:
- 2016-01-15
Related products to: MAP4K5 antibody - middle region (ARP33101_P050)
Related articles to: MAP4K5 antibody - middle region (ARP33101_P050)
- Apigenin, a naturally occurring flavonoid with low toxicity, exhibits anticancer activity, yet its effects on microRNAs (miRNAs) and downstream gene networks in esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we evaluated apigenin's antitumor effects in TE-1 and Eca-109 cells, assessing proliferation, apoptosis, colony formation, and invasion. Differentially expressed miRNAs were identified via small RNA sequencing, and candidate target genes were predicted, annotated using GO and KEGG analyses, and validated by qRT-PCR, revealing miRNA-mediated regulatory mechanisms underlying apigenin's inhibitory effects in ESCC. Apigenin markedly suppressed cell proliferation, clonogenic growth, wound closure, and invasive capacity, while promoting apoptosis in a dose-dependent manner. In TE-1 cells, apigenin upregulated hsa-let-7c-3p, hsa-miR-374c-3p, hsa-miR-3177-3p hsa-miR-4454, and hsa-miR-4728-3p, while downregulating hsa-miR-573, hsa-miR-548az-5p, hsa-miR-33b-5p, hsa-miR-4479, and hsa-miR-3198. Correspondingly, tumor-associated target genes including , , , and were upregulated, whereas , , , and were suppressed. In Eca-109 cells, apigenin altered the expression of distinct miRNAs, including the upregulation of hsa-miR-891-5p, hsa-miR-3170, hsa-miR-4421, and hsa-miR-675-5p and the downregulation of hsa-miR-153, hsa-miR-3188, and hsa-miR-4435, thereby modulating key oncogenic targets such as , , and . Functional enrichment analyses indicated that apigenin-regulated genes are involved in multiple cancer-related pathways across cytoplasmic and nuclear compartments. Overall, these results suggest that apigenin suppresses ESCC progression via coordinated miRNA-mRNA regulation, highlighting its potential as a therapeutic agent. - Source: PubMed
Publication date: 2026/02/28
Amjad NoumanMajid MuhammadSun ZhaojianBasnet RajeshRasool KashafWu LinpingLi Zhiyuan - Mammalian cardiomyocytes become terminally-differentiated during the perinatal period. In rodents, cytokinesis ceases after a final division cycle immediately after birth. Nuclear division continues and most cardiomyocytes become binucleated by ∼11 days. Subsequent growth results from an increase in cardiomyocyte size. The mechanisms involved remain under investigation. Mitogen-activated protein kinases (MAPKs) regulate cell growth/death: extracellular signal-regulated kinases 1/2 (ERK1/2) promote proliferation, whilst c-Jun N-terminal kinases (JNKs) and p38-MAPKs respond to cellular stresses. We assessed their regulation in rat hearts during postnatal development (2, 7, 14, and 28 days, 12 weeks) during which time there was rapid, substantial downregulation of mitosis/cytokinesis genes (Cenpa/e/f, Aurkb, Anln, Cdca8, Orc6) with lesser downregulation of DNA replication genes (Orcs1-5, Mcms2-7). MAPK activation was assessed by immunoblotting for total and phosphorylated (activated) kinases. Total ERK1/2 was downregulated, but not JNKs or p38-MAPKs, whilst phosphorylation of all MAPKs increased relative to total protein albeit transiently for JNKs. These profiles differed from activation of Akt (also involved in cardiomyocyte growth). Dual-specificity phosphatases, upstream MAPK kinase kinases (MAP3Ks), and MAP3K kinases (MAP4Ks) identified in neonatal rat cardiomyocytes by RNASeq were differentially regulated during postnatal cardiac development. The MAP3Ks that we could assess by immunoblotting (RAF kinases and Map3k3) showed greater downregulation of the protein than mRNA. MAP3K2/MAP3K3/MAP4K5 were upregulated in human failing heart samples and may be part of the "foetal gene programme" of re-expressed genes in disease. Thus, MAPKs, along with kinases and phosphatases that regulate them, potentially play a significant role in postnatal remodelling of the heart. - Source: PubMed
Publication date: 2024/09/07
Alharbi Hajed OSugden Peter HClerk Angela - SARS-CoV-2 3C-like main protease (3CL) is essential for protein excision from the viral polyprotein. 3CL inhibitor drug development to block SARS-CoV-2 replication focuses on the catalytic non-prime (P) side for specificity and potency, but the importance of the prime (P') side in substrate specificity and for drug development remains underappreciated. We determined the P6-P6' specificity for 3CL from >800 cleavage sites that we identified using Proteomic Identification of Cleavage site Specificity (PICS). Cleavage occurred after the canonical P1-Gln and non-canonical P1-His and P1-Met residues. Moreover, P3 showed a preference for Arg/Lys and P3' for His. Essential H-bonds between the N-terminal Ser1 of protomer-B in 3CL dimers form with P1-His, but not with P1-Met. Nonetheless, cleavage occurs at P1-Met456 in native MAP4K5. Elevated reactive oxygen species in SARS-CoV-2 infection oxidize methionines. Molecular simulations revealed P1-Met forms an H-bond with Ser1 and notably, strong positive cooperativity between P1-Met with P3'-His was revealed, which enhanced peptide-cleavage rates. The highly plastic S3' subsite accommodates P3'-His that displays stabilizing backbone H-bonds with Thr25 lying central in a "'threonine trio" (Thr24-Thr25-Thr26) in the P'-binding domain I. Molecular docking simulations unveiled structure-activity relationships impacting 3CL-substrate interactions, and the role of these structural determinants was confirmed by MALDI-TOF-MS cleavage assays of P1'- and P3'-positional scanning peptide libraries carrying a 2nd optimal cut-site as an internal positive control. These data informed the design of two new and highly soluble 3CLquenched-fluorescent peptide substrates for improved FRET monitoring of 3CL activity with 15× improved sensitivity over current assays.IMPORTANCEFrom global proteomics identification of >800 cleavage sites, we characterized the P6-P6' active site specificity of SARS-CoV-2 3CL using proteome-derived peptide library screens, molecular modeling simulations, and focussed positional peptide libraries. In P1', we show that alanine and serine are cleaved 3× faster than glycine and the hydrophobic small amino acids Leu, Ile, or Val prevent cleavage of otherwise optimal non-prime sequences. In characterizing non-canonical non-prime P1 specificity, we explored the unusual P1-Met specificity, discovering enhanced cleavage when in the oxidized state (P1-Met). We unveiled unexpected amino acid cooperativity at P1-Met with P3'-His and noncanonical P1-His with P2-Phe, and the importance of the threonine trio (Thr24-Thr25-Thr26) in the prime side binding domain I in defining prime side binding in SARS-CoV-2 3CL. From these analyses, we rationally designed quenched-fluorescence natural amino acid peptide substrates with >15× improved sensitivity and high peptide solubility, facilitating handling and application for screening of new antiviral drugs. - Source: PubMed
Publication date: 2024/05/14
Cesar Ramos de Jesus HugoSolis NestorMachado YoanPablos IsabelBell Peter AKappelhoff ReinhildGrin Peter MSorgi Carlos AButler Georgina SOverall Christopher M - Signal transduction relies largely on the activity of kinases and phosphatases that control protein phosphorylation. However, we still know very little about phosphorylation-mediated signaling networks. Plant MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE KINASEs (MAP4Ks) have recently gained more attention, given their role in a wide range of processes, including developmental processes and stress signaling. We analyzed MAP4K expression patterns and mapped protein-MAP4K interactions in Arabidopsis (Arabidopsis thaliana), revealing extensive coexpression and heterodimerization. This heterodimerization is regulated by the C-terminal, intrinsically disordered half of the MAP4K, and specifically by the coiled coil motif. The ability to heterodimerize is required for proper activity and localization of the MAP4Ks. Taken together, our results identify MAP4K-interacting proteins and emphasize the functional importance of MAP4K heterodimerization. Furthermore, we identified MAP4K4/TARGET OF TEMPERATURE3 (TOT3) and MAP4K5/TOT3-INTERACTING PROTEIN 5 (TOI5) as key regulators of the transition from cell division to elongation zones in the primary root tip. - Source: PubMed
Pan LixiaFonseca de Lima Cassio FlavioVu Lam Daivan de Cotte BrigitteDe Winne NancyGevaert KrisDe Jaeger GeertDe Smet Ive - Posttranslational modifications (PTMs) are key regulatory events for the majority of signaling pathways. Transcription factors are often phosphorylated on multiple residues, which regulates their trafficking, stability, or transcriptional activity. Gli proteins, transcription factors that respond to the Hedgehog pathway, are regulated by phosphorylation, but the sites and the kinases involved have been only partially described. We identified three novel kinases: MRCKα, MRCKβ, and MAP4K5 which physically interact with Gli proteins and directly phosphorylate Gli2 on multiple sites. We established that MRCKα/β kinases regulate Gli proteins, which impacts the transcriptional output of the Hedgehog pathway. We showed that double knockout of MRCKα/β affects Gli2 ciliary and nuclear localization and reduces Gli2 binding to the Gli1 promoter. Our research fills a critical gap in our understanding of the regulation of Gli proteins by describing their activation mechanisms through phosphorylation. - Source: PubMed
Publication date: 2023/04/03
Baran BKosieradzka KSkarzynska WNiewiadomski P