Affinage

CLK2

Dual specificity protein kinase CLK2 · UniProt P49760

Length
499 aa
Mass
60.1 kDa
Annotated
2026-06-09
41 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CLK2 is a nuclear dual-specificity kinase that controls alternative pre-mRNA splicing by phosphorylating SR splicing factors and redistributing them from nuclear speckles (PMID:9637771, PMID:38009092). Its catalytic output and subnuclear positioning are governed by autophosphorylation: a conserved Ser141 site sets subnuclear localization (PMID:9852100), while autophosphorylation at T343 sustains kinase activity and, by suppressing liquid-liquid phase separation of an N-terminal intrinsically disordered region, prevents CLK2 condensates from sequestering splicing factors and driving intron retention (PMID:39119950). Through SR-protein phosphorylation CLK2 directs specific splicing programs, including tau exon 10 (PMID:16371011), the EMT-associated ENAH/MENA switch in breast cancer (PMID:25670169), the Hippo regulator AMOTL2 (PMID:38126343), RAE1 (PMID:39526400), and the SRSF9-dependent ARV7 splice variant in prostate cancer (PMID:39258426), making it an oncogenic kinase whose loss restrains tumor growth across multiple cancers (PMID:25670169, PMID:39526400). Beyond splicing, CLK2 functions as a signaling kinase: it is bound and phosphorylated by AKT at Ser34/Thr127 to promote cell survival after ionizing radiation (PMID:20682768), activates the phosphatase PTP-1B via Ser50 phosphorylation (PMID:10480872), and terminates NF-κB signaling by phosphorylating RelA/p65 at Ser180 to trigger its degradation and nuclear export (PMID:38724505). It modulates PP2A-dependent processes—suppressing CREB dephosphorylation to support UCP1-driven thermogenesis in brown adipose tissue (PMID:28089567) and restraining PP2A/B56β-mediated suppression of AKT/mTORC1 at synapses (PMID:26847545)—and stabilizes KEAP1 while downregulating p53 to suppress NRF2-driven ferroptosis in colorectal cancer (PMID:40882016). CLK2 kinase function is conserved, as human or murine CLK2 rescues the Drosophila DOA mitosis-to-meiosis switch defect in a manner requiring an intact catalytic domain (PMID:23376537).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1998 High

    Established CLK2 as a functional kinase by showing it is a nuclear dual-specificity enzyme that redistributes SR proteins and alters splicing, defining its core molecular role.

    Evidence Overexpression, nuclear localization assays, in vitro kinase and in vivo splicing assays

    PMID:9637771

    Open questions at the time
    • Endogenous physiological splicing targets not yet defined
    • No structural basis for SR-protein substrate recognition
  2. 1998 High

    Showed CLK2's own localization is self-regulated, linking autophosphorylation at Ser141 to subnuclear distribution and revealing kinase activity as a positioning switch.

    Evidence Site-directed mutagenesis, DRB inhibitor treatment, subcellular fractionation, endogenous protein analysis

    PMID:9852100

    Open questions at the time
    • Functional consequence of relocalization for splicing output not quantified
    • Other autophosphorylation sites not mapped here
  3. 1999 High

    Extended CLK2 substrates beyond splicing factors by identifying PTP-1B as a direct substrate activated through Ser50 phosphorylation, implicating CLK2 in tyrosine-phosphatase signaling.

    Evidence In vitro kinase/phosphatase assay, HEK293 co-expression, mutagenesis of Ser50

    PMID:10480872

    Open questions at the time
    • Physiological contexts where CLK2 activates PTP-1B unclear
    • Magnitude of effect modest (2-5 fold)
  4. 2003 Medium

    Connected CLK2 to cell cycle progression, apoptotic sensitivity, and telomere length, broadening its cellular role beyond splicing.

    Evidence Overexpression, siRNA, cell cycle/apoptosis assays, telomere length measurement

    PMID:12670948

    Open questions at the time
    • Molecular targets mediating cell-cycle and telomere effects unidentified
    • Reported pan-cellular and membrane-associated localization not mechanistically explained
  5. 2005 Medium

    Linked CLK2-dependent splicing to disease by correlating an inactive CLK2 isoform with altered tau exon 10 splicing in Alzheimer's brain.

    Evidence RT-PCR of postmortem human brain across regions

    PMID:16371011

    Open questions at the time
    • Correlative only, no direct CLK2 manipulation in this study
    • Causality between CLK2 isoform and tau splicing not established
  6. 2010 High

    Placed CLK2 downstream of AKT, showing direct AKT phosphorylation at Ser34/Thr127 drives radiation-induced survival and positioning CLK2 in a pro-survival signaling axis.

    Evidence In vitro kinase assay, Co-IP, AKT siRNA, CLK2 mutants, survival assays after irradiation

    PMID:20682768

    Open questions at the time
    • Downstream CLK2 substrates mediating survival not defined
    • Whether AKT phosphorylation alters CLK2 splicing activity unknown
  7. 2015 High

    Defined CLK2 as an oncogenic SR kinase in breast cancer whose loss triggers EMT splice-switching, providing a therapeutic rationale.

    Evidence shRNA, lentiviral viability screen, xenografts, RNA-seq splicing analysis

    PMID:25670169

    Open questions at the time
    • Direct SR-protein substrates driving ENAH switch not pinpointed
    • Generalizability across breast cancer subtypes partial
  8. 2016 High

    Revealed a CLK2-PP2A/B56β-AKT/mTORC1 axis at synapses, implicating CLK2 in Shank3-related neurodevelopmental dysfunction and as a drug target.

    Evidence Phosphoproteomics, CLK2 inhibition/knockdown, electrophysiology, mouse behavior

    PMID:26847545

    Open questions at the time
    • Direct CLK2 substrate on the PP2A pathway not fully resolved
    • Relationship to CLK2 splicing function unclear
  9. 2017 High

    Identified a CLK2-PP2A-CREB pathway controlling UCP1 transcription, establishing a metabolic thermogenic role in brown adipose tissue.

    Evidence Adipose-specific CLK2 knockout mice, oxygen consumption, p-CREB/UCP1 westerns, PP2A inhibitor rescue

    PMID:28089567

    Open questions at the time
    • Direct CLK2 phosphorylation target within the PP2A/CREB axis not mapped
    • Whether the same axis operates outside adipose tissue unknown
  10. 2019 High

    Showed CLK2 (with DYRK1A) modulates SR-protein phosphorylation, Wnt signaling, and chondrogenesis, extending its regulatory reach to MSC differentiation and inflammation.

    Evidence Kinase assays, siRNA in hMSCs/BEAS-2B, qPCR, rat OA model

    PMID:31132406

    Open questions at the time
    • Mechanism linking CLK2 to Wnt without β-catenin unresolved
    • Direct CLK2 targets in chondrogenesis unidentified
  11. 2019 High

    Demonstrated cross-species conservation of CLK2 kinase function by rescuing the Drosophila DOA mitosis-to-meiosis switch with human/murine CLK2 requiring an intact catalytic domain.

    Evidence Drosophila genetics, cell-autonomy, rescue with human/murine CLK2, catalytic mutant

    PMID:23376537

    Open questions at the time
    • Substrates governing the meiotic switch not identified
    • Mammalian germline relevance not directly tested
  12. 2019 Medium

    Implicated Xenopus Clk2 in neural-versus-epidermal fate decisions via BMP/Smad and FGF/MAPK modulation, adding a developmental dimension.

    Evidence Overexpression in Xenopus explants/embryos, qPCR, p-Smad/p-MAPK westerns

    PMID:31270814

    Open questions at the time
    • No loss-of-function confirmation
    • Direct CLK2 substrates in the signaling cascade undefined
  13. 2020 Medium

    Identified 14-3-3τ as a CLK2 interactor protected from ubiquitination, linking CLK2 to PP2A/PI3K-AKT/FOXO3a signaling in glioma stem cells.

    Evidence IP partner identification, in vitro ubiquitination, PP2A activity, in vivo GSC growth

    PMID:33294266

    Open questions at the time
    • Whether CLK2 phosphorylates 14-3-3τ not established
    • Single-lab Co-IP without reciprocal structural validation
  14. 2023 High

    Defined CLK2 as a negative regulator of NF-κB by phosphorylating RelA/p65 at Ser180 to drive its degradation and nuclear export, establishing an IκBα-independent termination mechanism.

    Evidence Phosphosite mapping, knockdown/overexpression, ubiquitination and nuclear export assays, murine inflammation models

    PMID:38724505

    Open questions at the time
    • Ubiquitin ligase coupling Ser180 phosphorylation to degradation not identified
    • Kinetics relative to canonical IκBα feedback unclear
  15. 2023 High

    Linked CLK2 splicing control to the Hippo pathway by showing CLK2 inhibition produces an exon-skipped AMOTL2 isoform that activates YAP transcription.

    Evidence ReFRAME chemical screen, splicing analysis, YAP localization/phosphorylation, AMOTL2 mutants

    PMID:38126343

    Open questions at the time
    • SR factor mediating AMOTL2 exon skipping not specified
    • Direct vs indirect effect on YAP not fully dissected
  16. 2023 Medium

    Showed CLK2 inhibition induces RAE1 exon-9 skipping and NMD via reduced SRSF phosphorylation, defining a targetable splicing dependency in multiple myeloma.

    Evidence Knockdown/inhibitor, SRSF westerns, exon-skipping RT-PCR, NMD and RAE1 rescue, xenograft

    PMID:39526400

    Open questions at the time
    • Specific SRSF protein acting on RAE1 not identified
    • Single-lab validation
  17. 2023 Medium

    Established a translational control loop where USP10-driven PABPC1 deubiquitination enhances CLK2 mRNA translation to promote pancreatic cancer growth, identifying upstream regulation of CLK2 abundance.

    Evidence Co-IP, deubiquitination assay, PABPC1-CLK2 mRNA-eIF4G1 binding, ubiquitination mutants, xenografts

    PMID:37757903

    Open questions at the time
    • Generality of CLK2 translational regulation beyond PDAC unknown
    • Single-lab mechanism
  18. 2024 High

    Revealed that CLK2 undergoes heat-shock-induced LLPS in nuclear speckles via an N-terminal IDR, with T343 autophosphorylation sustaining activity and suppressing condensation—coupling phase behavior to splicing and intron retention.

    Evidence Phase separation assays, IDR/T343 mutants, speckle imaging, intron retention RNA analysis, glioma stem cell model

    PMID:39119950

    Open questions at the time
    • Physiological triggers of CLK2 LLPS beyond heat shock unclear
    • Quantitative link between condensate size and global splicing output incomplete
  19. 2024 Medium

    Confirmed that selective chemical inhibition of CLK2 reversibly reduces SR-protein phosphorylation and relocalizes both SR proteins and CLK2, validating kinase activity as the driver of nuclear distribution.

    Evidence Selective CLK1/2/4 probe SGC-CLK-1, phosphorylation/localization imaging, washout experiments

    PMID:38009092

    Open questions at the time
    • Probe is not CLK2-selective (CLK1/2/4)
    • Off-target contributions not fully excluded
  20. 2024 Medium

    Defined a CLK2/SRSF9/ARV7 axis showing CLK2 inhibition lowers SRSF9 and reduces oncogenic ARV7 splice variant in prostate cancer.

    Evidence CLK inhibitors, SRSF9 RNA-binding and splicing reporter assays, ARV7 and proliferation analysis

    PMID:39258426

    Open questions at the time
    • Whether CLK2 directly phosphorylates SRSF9 vs regulates its expression unclear
    • Inhibitors target multiple CLKs
  21. 2024 Medium

    Connected CLK2 to ferroptosis resistance by stabilizing KEAP1 to suppress NRF2 and downregulating p53/SLC7A11, identifying a redox-survival role in colorectal cancer.

    Evidence Knockdown/overexpression, KEAP1/NRF2/p53/SLC7A11 westerns, ferroptosis assays, organoids, xenografts

    PMID:40882016

    Open questions at the time
    • Mechanism by which CLK2 stabilizes KEAP1 (direct phosphorylation?) unresolved
    • Single-lab study
  22. 2024 Medium

    Proposed a conserved CLK2-WTAP phosphorylation event enhancing m6A methyltransferase activity, linking CLK2 to epitranscriptomic regulation and splicing-coupled dosage compensation.

    Evidence Drosophila DOA genetics, Sxl splicing/m6A assays, in vitro CLK2 phosphorylation of WTAP, phosphomimetics (preprint)

    PMID:bio_10.1101_2024.11.25.625202

    Open questions at the time
    • Not yet peer-reviewed
    • Functional impact of WTAP phosphorylation on m6A in human cells needs confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CLK2's diverse roles—splicing-factor phosphorylation, condensate formation, and direct phosphorylation of signaling substrates (PTP-1B, RelA, WTAP)—are integrated, prioritized, and selectively engaged in different tissues remains unresolved.
  • No unifying model coordinating splicing vs non-splicing substrate selection
  • Structural basis for substrate discrimination unknown
  • Tissue-specific determinants of CLK2 output undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016740 transferase activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 4 GO:0005654 nucleoplasm 2
Pathway
R-HSA-8953854 Metabolism of RNA 6 R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
AKT1PTPN1RELAWTAPYWHAQ

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Human CLK2 is a nuclear dual-specificity kinase that causes redistribution of SR proteins from nuclear speckles and regulates alternative splicing of a model pre-mRNA substrate in vivo. The truncated inactive isoform CLK2(T) colocalizes with SR proteins in nuclear speckles. Overexpression in cells, nuclear localization assays, in vitro kinase assay, in vivo splicing assay Experimental cell research High 9637771
1998 CLK2 cellular localization is regulated by autophosphorylation at serine 141 (a conserved site among all CLK proteins); site-directed mutagenesis of Ser141 alters subnuclear localization, and treatment with kinase inhibitor DRB causes CLK2 to change its nuclear distribution. Endogenous CLK2 is differentially phosphorylated in vivo compared to overexpressed protein. Site-directed mutagenesis, kinase inhibitor treatment, subcellular fractionation/localization assays, endogenous protein biochemical characterization The Journal of biological chemistry High 9852100
1999 CLK2 (and CLK1) directly phosphorylate and activate the protein-tyrosine phosphatase PTP-1B in vitro and in vivo. CLK2 phosphorylation of PTP-1B at Ser50 activates its phosphatase activity approximately 3–5-fold. Co-expression of CLK2 with PTP-1B in HEK293 cells stimulates phosphatase activity ~2-fold. In vitro kinase/phosphatase assay, co-expression in HEK293 cells, site-directed mutagenesis identifying Ser50 The Journal of biological chemistry High 10480872
2003 Human CLK2 (hCLK2) overexpression decreases cell cycle length, while inhibition of hCLK2 expression arrests the cell cycle reversibly. hCLK2 overexpression renders cells hypersensitive to apoptosis by oxidative stress or DNA replication block and gradually increases telomere length. hCLK2 is present in all cellular compartments and exists as both membrane-associated and soluble forms. Overexpression, siRNA knockdown, cell cycle analysis, apoptosis assays, telomere length measurement, subcellular fractionation The Journal of biological chemistry Medium 12670948
2005 CLK2 regulates alternative splicing of tau exon 10 in the brain. In sporadic Alzheimer's disease postmortem brain tissue, the amount of an inactive CLK2 isoform mRNA is increased in affected areas, correlating with altered tau exon 10 splicing patterns. RT-PCR analysis of postmortem human brain tissue for alternative splicing patterns of tau, htra2-beta, presenilin 2, and clk2 Journal of neurochemistry Medium 16371011
2010 AKT directly binds to and phosphorylates CLK2 at serine 34 and threonine 127, both in vitro and in vivo. Ionizing radiation induces CLK2 phosphorylation via AKT activation. CLK2 overexpression promotes cell survival after ionizing radiation in a manner dependent on phosphorylation at Ser34 and Thr127. In vitro kinase assay, co-immunoprecipitation, siRNA knockdown of AKT, overexpression of CLK2 mutants, cell survival assays after irradiation The Journal of biological chemistry High 20682768
2015 CLK2 acts as an oncogenic kinase in breast cancer: it phosphorylates SR proteins involved in splicing, and its downregulation inhibits breast cancer growth in cell culture and xenograft models. Loss of CLK2 in luminal breast cancer cells leads to upregulation of EMT-related genes and a switch to mesenchymal splice variants including ENAH/MENA. shRNA knockdown, lentiviral cell viability screen, xenograft models, splicing analysis by RNA-seq Cancer research High 25670169
2016 In Shank3-deficient neurons, elevated CLK2 levels lead to enhanced phosphorylation and activation of PP2A regulatory subunit B56β, which in turn suppresses AKT/mTORC1 signaling. Pharmacological inhibition or genetic knockdown of CLK2 relieves synaptic deficits in Shank3-deficient and PMDS patient-derived neurons, and restores sociability in Shank3-deficient mice. Quantitative phosphoproteomics, pharmacological CLK2 inhibition, genetic CLK2 knockdown, synaptic electrophysiology, mouse behavioral assays Science High 26847545
2017 CLK2 is expressed in brown adipose tissue (BAT) and upregulated upon refeeding. Adipose-specific CLK2 knockout mice exhibit decreased energy expenditure and reduced UCP1 protein levels. CLK2 promotes CREB phosphorylation by inhibiting PP2A-mediated CREB dephosphorylation, thereby supporting UCP1 transcription and diet-induced thermogenesis. Adipose-specific CLK2 knockout mice, tissue oxygen consumption assay, western blot for UCP1 and p-CREB, PP2A inhibitor rescue experiment Cell metabolism High 28089567
2019 CLK2 inhibits CLK2-mediated phosphorylation of SR splicing factors and DYRK1A-mediated phosphorylation of SIRT1 and FOXO1. siRNA knockdown of CLK2 modulates the Wnt pathway (without affecting β-catenin) and induces early chondrogenesis in hMSCs. Combined CLK2/DYRK1A knockdown enhances anti-inflammatory effects beyond either alone. Biochemical kinase activity assays, western blot for SR protein phosphorylation, siRNA knockdown in hMSCs and BEAS-2B cells, qPCR for Wnt pathway and chondrogenic genes, in vivo rat OA model Osteoarthritis and cartilage High 31132406
2019 Drosophila DOA (CLK2 ortholog) is required cell-autonomously for the mitosis-to-meiosis switch in spermatogenesis. Human or murine CLK2 can rescue germline overproliferation and fertility in Doa mutant flies, and this rescue requires a conserved residue in the kinase catalytic domain. Drosophila genetic screen, cell-autonomy experiments, rescue by human/murine CLK2 expression, catalytic domain mutant analysis Developmental biology High 23376537
2019 Xenopus Clk2 promotes early neural development and inhibits epidermis differentiation. Clk2 overexpression in ectodermal explants induces neural marker genes, expands the neural plate at the expense of epidermal ectoderm, downregulates p-Smad1/5/8 in cooperation with BMP inhibition, and increases activated MAPK together with FGF signaling. Overexpression in Xenopus ectodermal explants and whole embryos, qPCR for neural/epidermal markers, western blot for p-Smad1/5/8 and p-MAPK Development, growth & differentiation Medium 31270814
2020 CLK2 binds to 14-3-3τ isoform and prevents its ubiquitination in glioma stem-like cells (GSCs). CLK2 knockdown increases PP2A activity and activates PI3K signaling. CLK2 knockdown blocks GSC growth in vivo through the AKT/FOXO3a/p27 pathway. Immunoprecipitation to identify binding partners, in vitro ubiquitination assay, PP2A activity assay, in vivo GSC growth assay American journal of cancer research Medium 33294266
2023 CLK2 phosphorylates the RelA/p65 subunit of NF-κB at Ser180 in the nucleus, leading to ubiquitin-proteasome-mediated degradation and cytoplasmic redistribution of RelA/p65, thereby mediating IκBα-independent early termination of NF-κB activation. CLK2 depletion increases inflammatory cytokine production. Phosphorylation site mapping, CLK2 knockdown/overexpression, ubiquitination assays, nuclear export assays, murine in vivo inflammation models Nature communications High 38724505
2023 CLK2 inhibition promotes alternative splicing of the Hippo pathway protein AMOTL2, producing an exon-skipped isoform that cannot associate with membrane-bound proteins, resulting in decreased phosphorylation and membrane localization of YAP and activation of YAP-driven transcription. High-throughput chemical screen (ReFRAME library), splicing analysis, YAP localization and phosphorylation assays, AMOTL2 mutant constructs eLife High 38126343
2023 CLK2 inhibition suppresses SRSF phosphorylation and induces exon 9 skipping of RAE1, resulting in nonsense-mediated mRNA decay (NMD) of RAE1 mRNA, which inhibits multiple myeloma cell proliferation. RAE1 overexpression partially reverses the antitumor effect of CLK2 knockdown. CLK2 knockdown and inhibitor treatment, SRSF phosphorylation western blot, exon-skipping RT-PCR, NMD assay, RAE1 rescue experiment, xenograft model Cancer science Medium 39526400
2023 USP10 deubiquitinates PABPC1 at K27/29-linked ubiquitination in its RRM2 domain. Deubiquitinated PABPC1 associates more efficiently with CLK2 mRNA and eIF4G1, increasing CLK2 translation efficiency and promoting pancreatic ductal adenocarcinoma tumor growth. Co-IP (USP10–PABPC1 interaction), deubiquitination assay, mRNA-protein interaction assay (PABPC1–CLK2 mRNA–eIF4G1), PABPC1 ubiquitination mutant rescue, xenograft models Cancer letters Medium 37757903
2024 CLK2 undergoes liquid-liquid phase separation (LLPS) within nuclear speckles in response to heat shock, dependent on an intrinsically disordered region (IDR) in N-terminal amino acids 1–148. Autophosphorylation at T343 sustains kinase activity and inhibits LLPS of the IDR. CLK2 condensates reorganize nuclear speckles into larger rounded structures, recruit splicing factors, restrict their access to mRNA, and promote intron retention. Phase separation assays, IDR deletion mutants, T343 phosphorylation site mutagenesis, nuclear speckle imaging, intron retention RNA analysis, glioma stem cell model Advanced science High 39119950
2024 CLK2 inhibition by small-molecule CLK inhibitors (cirtuvivint or lorecivivint) reduces expression of SRSF9, which binds the ARV7 3'UTR cryptic exon and promotes its inclusion. Disrupting the CLK2/SRSF9 axis decreases ARV7 splice variant expression in prostate cancer models. CLK inhibitor treatment, SRSF9 RNA-binding assays, splicing reporter assays, ARV7 expression analysis, anti-proliferative assays Molecular oncology Medium 39258426
2024 CLK2 stabilizes KEAP1 protein to suppress NRF2 activity, resulting in downregulation of HMOX1 and SLC7A11. Simultaneously, CLK2 downregulates p53, relieving p53-mediated repression of SLC7A11. Absence of CLK2 leads to excessive HMOX1 activation and sensitization of colorectal cancer cells to ferroptosis. CLK2 knockdown/overexpression, KEAP1/NRF2 pathway western blot, p53 analysis, ferroptosis assays, patient-derived organoids, xenograft models Cancer research Medium 40882016
2024 SGC-CLK-1 (CAF-170) reduces SR protein phosphorylation and reversibly alters SR protein and CLK2 subcellular localization, demonstrating that CLK2 kinase activity regulates its own and SR protein nuclear distribution. Pharmacological inhibition with selective CLK1/2/4 probe, phosphorylation assays, subcellular localization imaging, washout (reversibility) experiments Current research in chemical biology Medium 38009092
2024 Drosophila DOA (CLK2 ortholog) phosphorylates Fl(2)d (human WTAP homolog) at a conserved site in a helical structure to enhance m6A mRNA methyltransferase complex activity. CLK2 phosphorylates WTAP at the same conserved helix. Phosphorylation at this site is required for m6A deposition and correct Sxl alternative splicing for sex determination/dosage compensation. Drosophila genetics (DOA mutants), Sxl splicing assay, m6A deposition measurement, CLK2 in vitro phosphorylation of WTAP, phosphomimetic mutants, human cell dosage compensation gene regulation assay bioRxivpreprint Medium bio_10.1101_2024.11.25.625202

Source papers

Stage 0 corpus · 41 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Modulation of the Wnt pathway through inhibition of CLK2 and DYRK1A by lorecivivint as a novel, potentially disease-modifying approach for knee osteoarthritis treatment. Osteoarthritis and cartilage 145 31132406
2016 CLK2 inhibition ameliorates autistic features associated with SHANK3 deficiency. Science (New York, N.Y.) 127 26847545
1998 The Clk2 and Clk3 dual-specificity protein kinases regulate the intranuclear distribution of SR proteins and influence pre-mRNA splicing. Experimental cell research 127 9637771
2005 The alternative splicing of tau exon 10 and its regulatory proteins CLK2 and TRA2-BETA1 changes in sporadic Alzheimer's disease. Journal of neurochemistry 118 16371011
2015 CLK2 Is an Oncogenic Kinase and Splicing Regulator in Breast Cancer. Cancer research 95 25670169
2021 A Phase 2b randomized trial of lorecivivint, a novel intra-articular CLK2/DYRK1A inhibitor and Wnt pathway modulator for knee osteoarthritis. Osteoarthritis and cartilage 87 33588087
1999 The CLK family kinases, CLK1 and CLK2, phosphorylate and activate the tyrosine phosphatase, PTP-1B. The Journal of biological chemistry 64 10480872
2001 The C. elegans maternal-effect gene clk-2 is essential for embryonic development, encodes a protein homologous to yeast Tel2p and affects telomere length. Development (Cambridge, England) 54 11641227
2017 The Discovery of a Dual TTK Protein Kinase/CDC2-Like Kinase (CLK2) Inhibitor for the Treatment of Triple Negative Breast Cancer Initiated from a Phenotypic Screen. Journal of medicinal chemistry 50 28991472
1998 The cellular localization of the murine serine/arginine-rich protein kinase CLK2 is regulated by serine 141 autophosphorylation. The Journal of biological chemistry 49 9852100
2017 Adipose Tissue CLK2 Promotes Energy Expenditure during High-Fat Diet Intermittent Fasting. Cell metabolism 48 28089567
2001 Functional hemizygosity of PAFAH1B3 due to a PAFAH1B3-CLK2 fusion gene in a female with mental retardation, ataxia and atrophy of the brain. Human molecular genetics 48 11285245
2006 Abrogation of the CLK-2 checkpoint leads to tolerance to base-excision repair intermediates. EMBO reports 43 16964178
2010 Phosphorylation of CLK2 at serine 34 and threonine 127 by AKT controls cell survival after ionizing radiation. The Journal of biological chemistry 35 20682768
2003 Human CLK2 links cell cycle progression, apoptosis, and telomere length regulation. The Journal of biological chemistry 35 12670948
2001 C. elegans clk-2, a gene that limits life span, encodes a telomere length regulator similar to yeast telomere binding protein Tel2p. Current biology : CB 35 11696330
2020 Dual TTK/CLK2 inhibitor, CC-671, selectively antagonizes ABCG2-mediated multidrug resistance in lung cancer cells. Cancer science 31 32478948
2023 Deubiquitinating PABPC1 by USP10 upregulates CLK2 translation to promote tumor progression in pancreatic ductal adenocarcinoma. Cancer letters 26 37757903
2013 The highly conserved LAMMER/CLK2 protein kinases prevent germ cell overproliferation in Drosophila. Developmental biology 25 23376537
2018 CLK2 blockade modulates alternative splicing compromising MYC-driven breast tumors. EMBO molecular medicine 20 29789342
2018 Exercise decreases CLK2 in the liver of obese mice and prevents hepatic fat accumulation. Journal of cellular biochemistry 17 29575149
2024 CLK2 mediates IκBα-independent early termination of NF-κB activation by inducing cytoplasmic redistribution and degradation. Nature communications 14 38724505
2022 CLK1/CLK2-driven signalling at the Leishmania kinetochore is captured by spatially referenced proximity phosphoproteomics. Communications biology 12 36437406
2020 Depletion of CLK2 sensitizes glioma stem-like cells to PI3K/mTOR and FGFR inhibitors. American journal of cancer research 11 33294266
2019 Cdc2-like kinase 2 (Clk2) promotes early neural development in Xenopus embryos. Development, growth & differentiation 11 31270814
2024 CLK2 Condensates Reorganize Nuclear Speckles and Induce Intron Retention. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 9 39119950
2023 CLK2 and CLK4 are regulators of DNA damage-induced NF-κB targeted by novel small molecule inhibitors. Cell chemical biology 9 37506701
2025 CLK2 Regulates the KEAP1/NRF2 and p53 Pathways to Suppress Ferroptosis in Colorectal Cancer. Cancer research 6 40882016
2024 A novel selenium nanocomposite modified by AANL inhibits tumor growth by upregulating CLK2 in lung cancer. Bioorganic chemistry 6 38761707
2021 CLK2 promotes occurrence and development of non-small cell lung cancer. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 6 33721432
2024 Targeting the CLK2/SRSF9 splicing axis in prostate cancer leads to decreased ARV7 expression. Molecular oncology 5 39258426
2024 Structure-Guided Discovery of Potent and Selective CLK2 Inhibitors for the Treatment of Knee Osteoarthritis. Journal of medicinal chemistry 4 38500250
2023 SGC-CLK-1: A chemical probe for the Cdc2-like kinases CLK1, CLK2, and CLK4. Current research in chemical biology 4 38009092
2024 In silico identification of a novel Cdc2-like kinase 2 (CLK2) inhibitor in triple negative breast cancer. Protein science : a publication of the Protein Society 3 38723164
2023 Pharmacological inhibition of CLK2 activates YAP by promoting alternative splicing of AMOTL2. eLife 3 38126343
2024 Targeting CLK2 and serine/arginine-rich splicing factors inhibits multiple myeloma through downregulating RAE1 by nonsense-mediated mRNA decay mechanism. Cancer science 2 39526400
2025 Discovery of novel pyridine skeleton derivatives as potent CLK2/3 inhibitors. Bioorganic & medicinal chemistry letters 0 40164394
2025 CLK2-SOX3 combination promotes choroidal neovascularization by SGLT1 inducing endothelial cell metabolic reprogramming. Cellular signalling 0 40373839
2023 Pharmacological inhibition of CLK2 activates YAP by promoting alternative splicing of AMOTL2. bioRxiv : the preprint server for biology 0 37131806
2023 CLK2 in GABAergic neurons is critical in regulating energy balance and anxiety-like behavior in a gender-specific fashion. Frontiers in endocrinology 0 37635967
2020 [Effect of aerobic exercise on the expression of CLK2 protein in liver of mice fed with high fat diet]. Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 0 32476369

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