CLK3 Mouse Monoclonal Antibody
- Known as:
- CLK3 Mouse Monoclonal Antibody
- Catalog number:
- BIN-001198-M01
- Product Quantity:
- 0.1mg
- Category:
- -
- Supplier:
- Zyagen
- Gene target:
- CLK3 Mouse Monoclonal Antibody
Related genes to: CLK3 Mouse Monoclonal Antibody
- Gene:
- CLK3 NIH gene
- Name:
- CDC like kinase 3
- Previous symbol:
- -
- Synonyms:
- clk3
- Chromosome:
- 15q24.1
- Locus Type:
- gene with protein product
- Date approved:
- 1998-02-11
- Date modifiied:
- 2016-10-05
Related products to: CLK3 Mouse Monoclonal Antibody
Related articles to: CLK3 Mouse Monoclonal Antibody
- Nuclear speckles (NS) are membraneless nuclear organelles that act as critical hubs for pre-messenger RNA splicing. Defects in splicing are linked to several human diseases, including cancer, Alzheimer's disease, and dystrophies. While CLK kinases regulate the mobilization of splicing factors from NS, the molecular mechanisms underlying NS assembly and dissolution remain unclear. Using an adaptation of the Biotinylation by Antibody Recognition technique, we identified polyphosphate (polyP) as a novel and essential regulator of NS dynamics. Polyphosphate, a highly conserved polyanion composed of a chain of phosphate molecules, is involved in several functions in mammalian cells. Here, we show that polyP interacts with the NS core component SRRM2, and its depletion disrupts NS organization releasing splicing factors into the nucleoplasm. RNA-seq analysis reveals that polyP depletion increases exon exclusion, particularly in transcripts with multiple isoforms, highlighting its role in splicing regulation. Mechanistically, we demonstrate that polyP acts as a physiological inhibitor of CLK3 kinase, preventing the phosphorylation of SR proteins and thereby maintaining NS stability. Our findings not only expand our understanding of NS biology but also provide new insights into the polyP involvement in splicing-related diseases. - Source: PubMed
Lázaro BlancaTadeo Francisco JRodríguez AndreaAyuso-Molina LucíaMartínez-Láinez Joan MarcQuandt EvaBernard MaribelBorghi FilipySaiardi AdolfoJuan-Mateu JonàsJiménez JavierClotet JosepBru Samuel - Dysregulated epigenetic control and DNA-repair defects are hallmarks of many cancers and neurodevelopmental disorders. ZMYM3, a chromatin-associated zinc-finger protein, orchestrates histone deacetylation, BRCA1-dependent homologous recombination (HR), and cytoskeletal organisation, yet the post-translational mechanisms that govern its activity remain largely unknown. Here we integrate global phosphoproteomics data to define the regulatory landscape of ZMYM3, with a focus on the highly recurrent phosphosite S464 located in its zinc-finger domain. S464 is detected in > 50% of curated human-cell-line datasets and is co-regulated with four upstream kinases (CDK13, HIPK1, CDK9, CLK3) and 15 binary interactors including BRCA1, HDAC6, and SWI/SNF components. Positively co-phosphorylated networks are enriched for chromatin remodelling, mitotic segregation, DNA-damage response, and cytoskeletal dynamics. cProSite analysis of patient tumours reveals striking S464 hyper-phosphorylation in breast and ovarian cancers, correlating with HR-deficiency signatures. ZMYM3 S464 emerges as a phospho-regulatory hub that coordinates epigenetic silencing, HR repair, and mitotic fidelity. Its cancer-type-specific upregulation offers a novel biomarker for HR-deficiency stratification and a therapeutic entry point for modulating BRCA1 function or epigenetic drug sensitivity; functional validation in HR-deficient models is now warranted. - Source: PubMed
Publication date: 2026/01/06
Pai ApoorvaMahin AlthafUmmar SamseeraGopalakrishnan Athira PerunellyShivamurthy Prathik BasthikoppaRajeev Athira CRaju Rajesh - Alternative splicing is a key regulator of immune regulation by enabling rapid and context-specific responses. However, the role of splicing regulators such as CDC-like kinase 1 (CLK1) in monocyte biology remains poorly defined. Here, we identify and characterize distinct CLK1-splice isoforms in human CD14 monocytes using long-read RNA sequencing. In resting monocytes, we observe predominant expression of a truncated isoform lacking exon 4 (CLK1Δ4), which undergoes nonsense-mediated decay resulting in minimal protein output. Lipopolysaccharide (LPS) stimulation induces a shift toward the full-length isoform (CLK1+4), associated with increased transcript stability and protein expression. This splicing switch was confirmed by RT-qPCR, short-read RNA sequencing, and Western blot analysis. Pharmacological inhibition of CLK1 selectively reduced TNFα production without affecting cell viability, implicating that the isoform shift enhances pro-inflammatory signaling. These findings uncover a stimulus-dependent splicing mechanism that modulates monocyte activation through differential CLK1 isoform expression and suggest a potential therapeutic avenue by targeting splicing regulators in immune-related disease with an established role of activated monocytes. - Source: PubMed
Publication date: 2025/12/03
van Haaren Maurice J HBodelón AlejandraSijbers Lyanne J P MScholman RiannePicavet Lucas WCalis Jorg J AVastert Sebastiaan Jvan Loosdregt Jorg - Compound BHBC-01, a promising multi-target inhibitor of Dyrk1A, Dyrk1B, and Clk1, which is based on 5-hydroxybenzo[b]thiophene-2-carboxylic acid benzylamide scaffold, has demonstrated its potential as a novel anticancer agent. To support its further development, this study investigated its pharmacokinetic and stability profiles. An ultra-high performance liquid chromatography-tandem mass spectrometry method was developed and validated for the analysis of compound BHBC-01. Chromatographic separation was achieved using an ACQUITY UPLC BEH C18 column with gradient elution, employing a mobile phase consisting of 0.1 % formic acid in water and acetonitrile at a flow rate of 0.4 mL/min. Diphenhydramine was used as the internal standard. Electrospray ionization in positive ion mode allowed multiple reaction monitoring detection using parent ions ([M + H]) at m/z 314.096 and m/z 256.14, and daughter ions at m/z 120.94 and m/z 167.04 for compound BHBC-01 and diphenhydramine, respectively. The bioanalytical method was validated according to US-FDA guidelines, demonstrating good linearity (50-1000 ng/mL), accuracy, precision, specificity, and stability, with a lower limit of quantification of 50 ng/mL. This method was applied to evaluate the in vitro metabolic stability of compound BHBC-01 in rat liver S9 fraction, revealing a half-life time of 1.95 h and an intrinsic clearance of 11.94 mL/min/kg, indicating stability against biotransformation. Compound BHBC-01 also exhibited significant stability in human plasma, with a half-life time of 57.7 h. Furthermore, gastrointestinal stability studies in simulated gastric and intestinal fluids demonstrated half-lives of 13.75 and 14.11 h, respectively, supporting its suitability for oral administration. In vivo pharmacokinetic studies were conducted in Sprague-Dawley rats following intravenous (5 mg/kg) and oral (30 mg/kg) administration. According to the findings, the compound demonstrates adequate pharmacokinetic characteristics through both intravenous and oral routes. The intravenous route demonstrated a C of 545.40 ng/mL, an AUC of 434.01 ng*h/mL, and a half-life time of 0.66 h. Oral administration showed higher C (657 ng/mL), and a half-life time of 7.18 h. The oral bioavailability (F) was calculated to be 19.62 %. Collectively, these findings highlight compound BHBC-01's favorable pharmacokinetic and stability profiles, supporting its potential as a drug candidate for further clinical development as a multi-target anticancer agent. - Source: PubMed
Publication date: 2025/12/03
Soliman MaryamMostafa NohaMahmoud Sally TarekEl-Gamil Dalia SAbdel-Halim MohammadFouad Marwa - The family of Cdc2-like kinases (CLKs) plays a critical role in regulating both constitutive and alternative pre-mRNA splicing. Of particular interest, CLKs exhibit unique thermosensitive properties characterized by increased activity at lower physiological temperatures. In this study, we integrate phylogenetic, protein-interaction, and structural analyses to investigate the evolutionary history and functional adaptation of CLKs across protista, fungi, plants, and metazoans. Our phylogenetic analysis, comprising 149 CLK homologs from 86 species, traces this gene back to the last eukaryotic common ancestor. The results reveal lineage-specific patterns of gene duplication and loss, including complete loss of CLKs in seven protist lineages and in microsporidian fungi. Interolog mapping identified 92 conserved CLK-interacting proteins across diverse species. In metazoans, these conserved interactors are primarily involved in complex splicing regulation, whereas in yeast they are associated with simplified RNA-processing mechanisms. Comparative structural modeling shows strong conservation of the kinase domain throughout eukaryotes, although notable divergence occurs in some Fungal and Protista lineages. Intrinsic disorder in the CLK N terminus emerges as a conserved structural property; however, sequence variability in this region modulates kinase activity and substrate specificity. Structural conservation in the activation segment, the core driver of CLK thermosensitivity, is observed across all eukaryotic kingdoms, though deviations were identified in various protist and plant lineages. Deleterious mutations often occur in this region following a duplication or preceding complete gene loss. Finally, species-specific temperature activity profiles underscore the adaptive evolution of CLKs, enabling organisms to thrive in diverse environmental conditions, including extreme temperatures. - Source: PubMed
Publication date: 2025/11/26
Ogle Rachel ANetherton Jacob KRobinson Benjamin RHeyd FlorianBaker Mark A