Affinage

TAOK2

Serine/threonine-protein kinase TAO2 · UniProt Q9UL54

Length
1235 aa
Mass
138.3 kDa
Annotated
2026-06-10
100 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TAOK2 (TAO2/PSK) is a STE20-family serine/threonine MAP3K that couples stress and cytoskeletal cues to MAPK signaling and that organizes microtubule, ER, and neuronal architecture (PMID:10497253, PMID:11279118). As a MAP3K it selectively activates the stress-responsive p38 and JNK pathways by binding and phosphorylating MEK3 and MEK6 (and MKK4/MKK7), while sparing ERK; its kinase domain has been crystallized in an active, autophosphorylated conformation that phosphorylates MEK6 within a defined motif (PMID:10497253, PMID:11279118, PMID:15458637). Beyond canonical MAPK signaling, TAOK2 binds TAK1 and selectively interferes with the TAK1–IKK interaction to restrain NF-κB activation during osmotic stress (PMID:16893890). TAOK2 is also a cytoskeletal organizer: its kinase-independent C-terminal tail binds and stabilizes microtubules into acetylated, nocodazole-resistant cables, and the same tail together with transmembrane and amphipathic regions tethers ER subdomains to growing microtubule plus ends (PMID:12639963, PMID:34879262). In neurons, TAOK2 acts downstream of Sema3A/Neuropilin-1 and upstream of JNK1 and RhoA to drive basal dendrite formation, cortical neuronal migration, and spine maturation, the last via direct phosphorylation of Septin7 that recruits it to spines to stabilize PSD95 (PMID:22683681, PMID:28065648, PMID:29467497, PMID:36123424). A nuclear pool localizes to nuclear speckles where its kinase activity maintains speckle integrity and supports pre-mRNA splicing and mRNA export (PMID:35704758), and TAOK2 additionally acts as an eEF2K-independent translational brake by directly phosphorylating eEF2 at Thr56 (PMID:38608030). De novo TAOK2 mutations and 16p11.2 deletion link the gene to autism-spectrum neurodevelopmental phenotypes through impaired protein stability, kinase activity, dendrite growth, and synapse development (PMID:29467497, PMID:36123424).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 High

    Established TAOK2 as a MAP3K by showing it selectively activates and binds stress-pathway MAP kinase kinases, defining its position upstream of p38/JNK signaling.

    Evidence Recombinant kinase assays, copurification with MEK3 from Sf9 cells, and MEK-binding domain mapping with chimeric MEKs

    PMID:10497253

    Open questions at the time
    • Did not establish which physiological stimuli engage this kinase in cells
    • In vitro substrate selectivity not yet validated for endogenous complexes
  2. 2000 High

    Showed TAOK2 activates the JNK pathway and that its C-terminus and kinase activity drive vesicular localization and actin stress fiber loss, linking the kinase to cytoskeletal remodeling.

    Evidence Immunoprecipitation kinase assay, transfection reporter assays, microinjection with live imaging, and truncation/kinase-dead mutants

    PMID:10660600

    Open questions at the time
    • Direct cytoskeletal substrate not identified
    • Mechanism connecting kinase activity to actin disassembly unresolved
  3. 2001 High

    Demonstrated endogenous TAOK2 selectively activates p38 and JNK (not ERK) via MEK3/6 and is induced by osmotic/microtubule stress and myoblast differentiation, framing it as a stress- and cytoskeleton-responsive kinase.

    Evidence Cell overexpression with reporter/western readouts, reciprocal co-IP, and in vitro kinase assays under sorbitol/NaCl/Taxol/nocodazole

    PMID:11279118

    Open questions at the time
    • Upstream sensor that activates TAOK2 under stress not defined
    • Link between microtubule perturbation and kinase activation mechanistic only by correlation
  4. 2004 High

    Resolved how TAOK2 is catalytically activated and recognizes substrate, providing the structural basis for STE20-family activation by phosphorylation.

    Evidence X-ray crystallography of the active kinase domain with structure-based mutagenesis and in vitro kinase assays

    PMID:15458637

    Open questions at the time
    • Structure limited to isolated kinase domain
    • Full-length regulatory architecture not visualized
  5. 2003 High

    Identified a kinase-independent microtubule-binding and -stabilizing function in the C-terminus and tubulin as a direct substrate, distinguishing TAOK2's scaffolding role from its catalytic role.

    Evidence Immunofluorescence colocalization with nocodazole challenge, domain/kinase-dead mutants, and in vitro tubulin binding/phosphorylation

    PMID:12639963

    Open questions at the time
    • Functional consequence of tubulin phosphorylation undefined
    • Relationship between MT stabilization and MAPK signaling unresolved
  6. 2006 High

    Defined a pathway-selective brake on innate signaling: TAOK2 binds TAK1 and blocks the TAK1–IKK interaction to suppress NF-κB without affecting TAK1-driven JNK.

    Evidence Binding screen, reciprocal co-IP, and NF-κB/JNK reporter assays under osmotic stress

    PMID:16893890

    Open questions at the time
    • Whether inhibition requires TAOK2 kinase activity not established
    • Physiological setting of TAK1 antagonism in vivo unknown
  7. 2006 Medium

    Provided atomic detail of inhibitor binding to the TAOK2 ATP pocket, enabling structure-guided inhibitor design.

    Evidence X-ray crystallography of the kinase domain co-crystallized with staurosporine

    PMID:16761096

    Open questions at the time
    • Limited functional validation beyond structural description
    • Selectivity over related kinases not addressed
  8. 2012 High

    Placed TAOK2 in a neurodevelopmental signaling axis, acting downstream of Sema3A/Nrp1 and upstream of JNK to direct basal dendrite and axon formation in vivo.

    Evidence In vivo cortical knockdown/overexpression, TAOK2-Nrp1 co-IP, and epistasis rescue with JNK readouts

    PMID:22683681

    Open questions at the time
    • Direct phosphorylation substrate in the dendrite pathway not identified
    • How Nrp1 engagement activates TAOK2 kinase activity unknown
  9. 2012 Medium

    Demonstrated functional conservation of TAOK2 in nervous-system behavior using a conditional knockout, linking the kinase to ethanol-response phenotypes.

    Evidence Nervous-system-specific conditional knockout mice with ethanol behavioral assays

    PMID:22883308

    Open questions at the time
    • Molecular mechanism underlying behavioral phenotype undefined
    • Strain-specific effects complicate interpretation
  10. 2017 High

    Identified Septin7 as a direct TAOK2 substrate whose phosphorylation drives spine localization and PSD95 stabilization, providing a molecular mechanism for spine maturation and calcium compartmentalization.

    Evidence Analog-sensitive kinase chemical genetics, MS phosphoproteomics, in vitro kinase assay, and calcium/spine imaging with knockdown

    PMID:28065648

    Open questions at the time
    • How Septin7 phosphorylation triggers its translocation mechanistically unresolved
    • Whether other spine substrates exist not addressed
  11. 2018 High

    Tied TAOK2 to RhoA activation and to autism-associated dysfunction, showing patient mutations and gene dosage perturb kinase activity, dendrite/synapse development, and cortical structure.

    Evidence Taok2 KO/het mice, RhoA activation assay with pharmacological rescue, and functional analysis of de novo ASD mutations

    PMID:29467497

    Open questions at the time
    • Direct effector linking TAOK2 to RhoA activation not identified
    • How distinct mutations differentially affect activity not fully mapped
  12. 2021 High

    Established TAOK2 as an ER–microtubule tether through its transmembrane/amphipathic and C-terminal MT-binding regions, with kinase activity governing ER morphology, ER-MT coupling, and cell division.

    Evidence Fractionation, live ER-dynamics imaging in KO cells, domain mapping, in vitro MT binding, and kinase-dead mutants

    PMID:34879262

    Open questions at the time
    • Substrate phosphorylated to regulate ER-MT tethering unidentified
    • Connection between ER tethering and MAPK/neuronal roles unexplored
  13. 2022 High

    Resolved a TAOK2α-specific role in cortical neuron migration upstream of JNK1, with constitutively active JNK1 rescuing migration defects in KO and 16p11.2 deletion models.

    Evidence Taok2 KO mice, in utero electroporation knockdown/overexpression, phospho-JNK1 westerns, and CA-JNK1 genetic rescue

    PMID:36123424

    Open questions at the time
    • Isoform-specific determinant of MT colocalization not pinned to a sequence element
    • Direct kinase substrate driving migration not defined
  14. 2022 High

    Uncovered a nuclear function: a speckle-localized TAOK2 pool whose kinase activity maintains speckle integrity and supports pre-mRNA splicing and nuclear export.

    Evidence Immunofluorescence, co-IP with SRSF1/Aly-Ref, siRNA and kinase inhibition with splicing/export and viral-replication readouts

    PMID:35704758

    Open questions at the time
    • Direct splicing/speckle substrate of TAOK2 not identified
    • How TAOK2 partitions between cytoplasmic and nuclear pools unknown
  15. 2022 Medium

    Listeria exploitation revealed TAOK2 kinase activity is required for pathogen vacuolar escape, with recruitment depending on listeriolysin O.

    Evidence High-content siRNA screen, pharmacological kinase inhibition, and imaging of vacuolar rupture

    PMID:32582947

    Open questions at the time
    • Host substrate mediating vacuolar rupture not identified
    • Mechanism of TAOK2 recruitment to vacuoles undefined
  16. 2024 High

    Defined an eEF2K-independent translational brake: TAOK2 directly phosphorylates eEF2 at Thr56 to repress elongation, linking the kinase to translational control disrupted in 16p11.2 deletion.

    Evidence Co-IP MS for translational machinery, in vitro kinase assay on eEF2, and translation assays in cells and mouse brain

    PMID:38608030

    Open questions at the time
    • Signals that engage TAOK2-dependent eEF2 phosphorylation not mapped
    • Crosstalk with eEF2K regulation unresolved
  17. 2016 Low

    Provided early pharmacological evidence linking TAOK2 kinase activity to autophagy in cancer cells.

    Evidence High-throughput inhibitor screen with SAR and autophagy assays

    PMID:27426302

    Open questions at the time
    • Indirect link between kinase inhibition and autophagy not mechanistically established
    • Compound selectivity for TAOK2 not validated
    • No autophagy substrate identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TAOK2's distinct subcellular pools (cytoplasmic MAPK signaling, microtubule/ER tethering, nuclear speckles, translational machinery) are coordinated and which upstream signals partition the kinase among them remains unknown.
  • No unifying model linking the kinase-dependent and kinase-independent functions
  • Direct substrates for several functions (ER tethering, splicing, migration) not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0008092 cytoskeletal protein binding 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005856 cytoskeleton 3 GO:0005654 nucleoplasm 1 GO:0005783 endoplasmic reticulum 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 1 R-HSA-392499 Metabolism of proteins 1 R-HSA-8953854 Metabolism of RNA 1
Partners
ALYREFEEF2MAP2K3MAP2K6MAP3K7NRP1SEPTIN7SRSF1

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 TAO2 is a serine/threonine kinase that selectively activates MAP kinase kinases MEK3, MEK4, and MEK6 of stress-responsive MAPK pathways in vitro. TAO2 copurified with endogenous MEK3 in Sf9 cells. The MEK-binding domain was localized to an ~135-residue sequence just C-terminal to the catalytic domain; this domain binds MEK3 and MEK6 (but not MEKs 1, 2, or 4) via the MEK N-terminus. Catalytic activity of full-length TAO2 enhanced MEK binding. Recombinant protein kinase assay, copurification from Sf9 cells, MEK-binding domain mapping with chimeric MEK proteins The Journal of biological chemistry High 10497253
2000 PSK (TAOK2) is a STE20-family serine/threonine kinase that activates MKK4 and MKK7 and thereby activates the JNK MAPK pathway when transfected into cells. Immunoprecipitated PSK phosphorylates myelin basic protein. Microinjection of PSK causes its localization to a vesicular compartment and a marked reduction in actin stress fibers; this requires the C-terminus (residues 1–1235 but not 1–349) and kinase activity (K57A mutant fails to reduce stress fibers). Immunoprecipitation kinase assay, transfection reporter assay, microinjection with live-cell imaging, kinase-dead and truncation mutants The Journal of biological chemistry High 10660600
2001 TAO2 overexpression in cells activates endogenous JNK/SAPK and p38 but not ERK1/2. Cotransfection experiments showed selective activation of MEK3 and MEK6 but not MEKs 1, 4, or 7. Co-immunoprecipitation demonstrated that endogenous TAO2 specifically associates with MEK3 and MEK6. Sorbitol, NaCl, Taxol, and nocodazole increase TAO2 activity toward itself and kinase-dead MEK3/6. Endogenous TAO2 activity is also induced during C2C12 myoblast differentiation in parallel with p38 activation. Overexpression in cells with reporter/western assays, co-immunoprecipitation, in vitro kinase assay with osmo/chemical stresses, cell differentiation model The Journal of biological chemistry High 11279118
2003 PSK (TAOK2) colocalizes with microtubules in cells; this colocalization is disrupted by nocodazole. PSK association with microtubules produces stabilized, perinuclear, nocodazole-resistant microtubule cables enriched in acetylated alpha-tubulin. Kinase-dead PSK (K57A) or the isolated C-terminus (residues 745–1235) lacking the kinase domain are sufficient for microtubule binding and stabilization. The N-terminus (1–940) alone cannot bind or stabilize microtubules. PSK binds and phosphorylates alpha- and beta-tubulin in vitro. Immunofluorescence colocalization, nocodazole treatment, kinase-dead and domain truncation mutants, in vitro binding/phosphorylation assay The Journal of biological chemistry High 12639963
2004 Crystal structure of the TAO2 kinase domain (residues 1–320) solved in its phosphorylated active conformation. Structure-based mutagenesis revealed that positively charged residues in the substrate-binding groove mediate the first phosphorylation step of MEK6 (on threonine in the motif DS*VAKT*I). Comparison with low-activity PAK1 reveals how Ste20p-family kinases are activated by phosphorylation. Active TAO2 displays unusual ATP interactions involving a subgroup-specific C-terminal extension. X-ray crystallography, structure-based mutagenesis, in vitro kinase assay Structure High 15458637
2006 TAO2 associates with TAK1 (MAP3K) and inhibits TAK1-mediated NF-κB activation but not TAK1-mediated JNK activation during osmotic stress. TAO2 interferes with the interaction between TAK1 and IKK, providing a mechanism for pathway-selective TAK1 signaling. TAO2 was identified as a TAK1-binding protein in a binding screen. Binding screen, co-immunoprecipitation, cell-based NF-κB and JNK reporter assays, osmotic stress treatment The Journal of biological chemistry High 16893890
2006 Crystal structure of the TAO2 kinase domain bound to staurosporine reveals that the inhibitor occupies the ATP adenosine-binding site. Staurosporine induces limited conformational changes around the binding pocket. The structure provides atomic detail for TAO2 inhibitor interactions. X-ray crystallography with staurosporine co-crystal Acta biochimica et biophysica Sinica Medium 16761096
2012 TAOK2 is essential for basal dendrite formation in cortical pyramidal neurons in vivo; knockdown impairs basal (but not apical) dendrites and axonal projections. TAOK2 interacts physically with Neuropilin-1 (Nrp1). TAOK2 overexpression rescues basal dendrite deficits in Nrp1(Sema-) neurons that cannot bind Sema3A, and rescues Nrp1-knockdown phenotypes in vivo. Sema3A and TAOK2 regulate basal dendrite formation through JNK activation, placing TAOK2 downstream of Sema3A/Nrp1 and upstream of JNK. In vivo knockdown/overexpression in cortical neurons, co-immunoprecipitation (TAOK2-Nrp1), epistasis rescue experiments, JNK pathway readouts Nature neuroscience High 22683681
2012 Conditional nervous-system-specific ablation of Taok2 in mice produces strain-specific alterations in ethanol-dependent behaviors (locomotor stimulation response to ethanol), functionally conserving the role of its Drosophila ortholog dtao. Conditional knockout (nervous system-specific Cre), behavioral assays for ethanol responses Genes, brain, and behavior Medium 22883308
2017 TAOK2 kinase activity is required for dendritic spine maturation. Using chemical genetics and mass spectrometry, TAOK2 was shown to directly phosphorylate Septin7 at an evolutionarily conserved residue. This phosphorylation induces Septin7 translocation to the spine, where Septin7 associates with and stabilizes PSD95, promoting spine maturation and compartmentalization of NMDA receptor-mediated calcium influx. TAOK2 depletion causes unstable dendritic protrusions, mislocalized shaft-synapses, and loss of calcium compartmentalization. Chemical genetics (analog-sensitive kinase), mass spectrometry phosphoproteomics, in vitro kinase assay, live-cell imaging of calcium, shRNA knockdown with spine morphology analysis Neuron High 28065648
2018 Loss of Taok2 activity in mice causes reduction in RhoA activation, and pharmacological enhancement of RhoA activity rescues synaptic phenotypes caused by Taok2 loss. De novo ASD mutations in TAOK2 impair protein stability and differentially affect kinase activity, dendrite growth, and spine/synapse development. Taok2 KO mice show dosage-dependent defects in brain size, neural connectivity, cortical layering, dendrite/synapse formation, and excitatory neurotransmission. Taok2 knockout/heterozygous mice, RhoA activation assay, pharmacological rescue, human cell functional analysis of patient mutations, behavioral assays Molecular psychiatry High 29467497
2021 TAOK2 localizes to distinct ER subdomains via transmembrane helices and an adjacent amphipathic region, and directly binds microtubules through its C-terminal tail, functioning as an ER-MT tether. In TAOK2 knockout cells, ER membrane dynamics increase but movement of ER along growing MT plus ends is disrupted. ER-MT tethering is regulated by TAOK2 kinase activity; perturbation of catalytic activity causes defects in ER morphology, ER-MT association, and cell division. Subcellular fractionation, live-cell imaging (ER dynamics), TAOK2 KO cells, domain mapping (transmembrane/amphipathic/C-terminal), in vitro MT binding, kinase-dead mutant analysis Developmental cell High 34879262
2022 TAOK2α isoform (but not TAOK2β) colocalizes with microtubules. Loss of Taok2 causes unstable microtubules with reduced acetylated tubulin and reduced phospho-JNK1. Taok2 KO and acute knockdown delay migration of upper-layer cortical neurons; expression of constitutively active JNK1 rescues these migration defects, placing TAOK2 upstream of JNK1 in neuronal migration. TAOK2α introduction into 16p11.2 heterozygous deletion mice (which have reduced p-JNK1) rescues neuronal migration deficits. Taok2 KO mice, in utero electroporation for acute knockdown/overexpression, immunostaining for cortical layering, phospho-JNK1 western blot, constitutively active JNK1 rescue, 16p11.2 del mouse model Molecular psychiatry High 36123424
2022 A nuclear pool of TAO2 localizes to nuclear speckles and interacts with nuclear speckle factors SRSF1 and Aly/Ref (involved in RNA splicing and nuclear export). Depletion or kinase inhibition of TAO2 disrupts nuclear speckle structure, decreases levels of SC35 and SON (speckle assembly/splicing proteins), and impairs pre-mRNA splicing and nuclear export of influenza M mRNA, reducing viral replication. Immunofluorescence localization, co-immunoprecipitation (TAO2 with SRSF1/Aly-Ref), siRNA depletion, kinase inhibitor treatment, western blot for SC35/SON, mRNA splicing/export assays, viral replication assay Proceedings of the National Academy of Sciences of the United States of America High 35704758
2022 Taok2 is required for vacuolar escape of Listeria monocytogenes in epithelial cells; siRNA knockdown of Taok2 reduces vacuolar rupture and cytoplasmic access of Listeria. Pharmacological inhibition of Taok2 kinase activity validated this role. Taok2 recruitment to Listeria vacuoles requires the pore-forming toxin listeriolysin O. High-content siRNA microscopy screen, pharmacological kinase inhibition, immunofluorescence imaging of Listeria vacuolar rupture The Journal of infectious diseases Medium 32582947
2024 TAOK2 associates with the translational machinery and directly phosphorylates eukaryotic elongation factor 2 (eEF2) at the same regulatory site (Thr56) as eEF2K, functioning as a translational brake. This pathway operates independently of eEF2K. Loss of TAOK2 (in 16p11.2 deletion models) leads to increased translation. This identifies an eEF2K-independent mechanism of translation elongation control. Proteomics (co-IP mass spectrometry for translational machinery association), in vitro kinase assay (direct eEF2 phosphorylation), translation assays in cultured cells and mouse brain, genetic models (16p11.2 deletion mice and cells) Science advances High 38608030
2016 Three small-molecule compounds identified by high-throughput screening (200,000 compounds) inhibit TAOK2 kinase activity and also inhibit autophagy, providing early evidence that TAOK2 kinase activity is required for autophagy in NSCLC cells. High-throughput kinase inhibitor screen, SAR analysis, autophagy assay Bioorganic & medicinal chemistry letters Low 27426302

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 CDK6 (PLSTIRE) and CDK4 (PSK-J3) are a distinct subset of the cyclin-dependent kinases that associate with cyclin D1. Oncogene 291 8302605
1984 Krestin (PSK). Cancer treatment reviews 243 6238674
2012 Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex. Nature neuroscience 141 22683681
2018 Altered TAOK2 activity causes autism-related neurodevelopmental and cognitive abnormalities through RhoA signaling. Molecular psychiatry 119 29467497
2017 TAOK2 Kinase Mediates PSD95 Stability and Dendritic Spine Maturation through Septin7 Phosphorylation. Neuron 113 28065648
2011 The phytosulfokine (PSK) receptor is capable of guanylate cyclase activity and enabling cyclic GMP-dependent signaling in plants. The Journal of biological chemistry 102 21504901
2002 Anticancer effects and mechanisms of polysaccharide-K (PSK): implications of cancer immunotherapy. Anticancer research 99 12168863
1990 Significant prolongation of disease-free period gained by oral polysaccharide K (PSK) administration after curative surgical operation of colorectal cancer. Cancer immunology, immunotherapy : CII 93 2198088
2004 Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer: a randomised controlled study. British journal of cancer 88 14997197
2000 PSK, a novel STE20-like kinase derived from prostatic carcinoma that activates the c-Jun N-terminal kinase mitogen-activated protein kinase pathway and regulates actin cytoskeletal organization. The Journal of biological chemistry 87 10660600
1999 Isolation of the protein kinase TAO2 and identification of its mitogen-activated protein kinase/extracellular signal-regulated kinase kinase binding domain. The Journal of biological chemistry 83 10497253
2008 Regulation of the Candida albicans cell wall damage response by transcription factor Sko1 and PAS kinase Psk1. Molecular biology of the cell 77 18434592
2011 TLR2 agonist PSK activates human NK cells and enhances the antitumor effect of HER2-targeted monoclonal antibody therapy. Clinical cancer research : an official journal of the American Association for Cancer Research 72 21918170
2012 Psk1, an AGC kinase family member in fission yeast, is directly phosphorylated and controlled by TORC1 and functions as S6 kinase. Journal of cell science 70 22976295
1991 Induction of immunopotentiation activity by a protein-bound polysaccharide, PSK (review). Anticancer research 69 2064356
1995 Antimetastatic effects of PSK (Krestin), a protein-bound polysaccharide obtained from basidiomycetes: an overview. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 67 7606203
2008 The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis. BMC cancer 65 18366723
2000 Protein-bound polysaccharide PSK inhibits tumor invasiveness by down-regulation of TGF-beta1 and MMPs. Clinical & experimental metastasis 61 11448066
2004 Crystal structure of the TAO2 kinase domain: activation and specificity of a Ste20p MAP3K. Structure (London, England : 1993) 59 15458637
2003 PSK-mediated NF-kappaB inhibition augments docetaxel-induced apoptosis in human pancreatic cancer cells NOR-P1. Oncogene 55 12687011
2001 Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2. The Journal of biological chemistry 55 11279118
2006 Osmotic stress activates the TAK1-JNK pathway while blocking TAK1-mediated NF-kappaB activation: TAO2 regulates TAK1 pathways. The Journal of biological chemistry 54 16893890
1997 Oral administration of PSK can improve the impaired anti-tumor CD4+ T-cell response in gut-associated lymphoid tissue (GALT) of specific-pathogen-free mice. International journal of cancer 51 9033641
2003 The prostate-derived sterile 20-like kinase (PSK) regulates microtubule organization and stability. The Journal of biological chemistry 50 12639963
2004 Effect of PSK on the maturation of dendritic cells derived from human peripheral blood monocytes. Immunology letters 47 15019294
1990 Gastroenteritis in suckling mice caused by human rotavirus can be prevented with egg yolk immunoglobulin (IgY) and treated with a protein-bound polysaccharide preparation (PSK). Microbiology and immunology 47 2176268
2003 A single gene on the staphylococcal multiresistance plasmid pSK1 encodes a novel partitioning system. Journal of bacteriology 44 12644483
2005 Effects of PSK on T and dendritic cells differentiation in gastric or colorectal cancer patients. Anticancer research 39 15816609
1998 Direct action of a protein-bound polysaccharide, PSK, on transforming growth factor-beta. Immunopharmacology 37 9858065
1993 PSK as a chemopreventive agent. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 36 8318880
1996 Enhancement of radical intensity and cytotoxic activity of ascorbate by PSK and lignins. Anticancer research 35 8917416
1988 Fate and distribution of an antitumor protein-bound polysaccharide PSK (Krestin). International journal of immunopharmacology 34 3170055
1991 In vitro immunomodulating effect of protein-bound polysaccharide, PSK on peripheral blood, regional nodes, and spleen lymphocytes in patients with gastric cancer. Cancer immunology, immunotherapy : CII 32 1901030
2019 Expression of a novel PSK-encoding gene from soybean improves seed growth and yield in transgenic plants. Planta 31 30756185
2010 Analysis of the prototypical Staphylococcus aureus multiresistance plasmid pSK1. Plasmid 30 20547176
1992 Randomized adjuvant trial to evaluate the addition of tamoxifen and PSK to chemotherapy in patients with primary breast cancer. 5-Year results from the Nishi-Nippon Group of the Adjuvant Chemoendocrine Therapy for Breast Cancer Organization. Cancer 29 1423177
2001 Plant polysaccharide PSK: cytostatic effects on growth and invasion; modulating effect on the expression of HLA and adhesion molecules on human gastric and colonic tumor cell surface. Anticancer research 28 11396133
2008 Analysis of the pSK1 replicon, a prototype from the staphylococcal multiresistance plasmid family. Microbiology (Reading, England) 27 18832314
2002 Different regulation of PKC isoenzymes and MAPK by PSK and IL-2 in the proliferative and cytotoxic activities of the NKL human natural killer cell line. Cancer immunology, immunotherapy : CII 27 12536241
1992 Activation of human natural killer cells by the protein-bound polysaccharide PSK independently of interferon and interleukin 2. Immunology letters 27 1372283
1991 Lysis of fresh human tumor cells by autologous peripheral blood lymphocytes and tumor-infiltrating lymphocytes activated by PSK. Japanese journal of cancer research : Gann 25 1938599
1992 The polysaccharide K (PSK) potentiates in vitro activation of the cytotoxic function in human blood lymphocytes by autologous tumour cells. Cancer immunology, immunotherapy : CII 23 1638556
1987 A biological response modifier, PSK, inhibits human immunodeficiency virus infection in vitro. Biochemical and biophysical research communications 23 2825669
2021 TAOK2 is an ER-localized kinase that catalyzes the dynamic tethering of ER to microtubules. Developmental cell 22 34879262
2012 Taok2 controls behavioral response to ethanol in mice. Genes, brain, and behavior 22 22883308
2004 PSK and Trx80 inhibit B-cell growth in EBV-infected cord blood mononuclear cells through T cells activated by the monocyte products IL-15 and IL-12. Blood 22 15507528
1997 Protein bound polysaccharide PSK abrogates more efficiently experimental metastases derived from H-2 negative than from H-2 positive fibrosarcoma tumor clones. Journal of experimental & clinical cancer research : CR 22 9505208
1991 Activation by the protein-bound polysaccharide PSK (krestin) of cytotoxic lymphocytes that act on fresh autologous tumor cells and T24 human urinary bladder transitional carcinoma cell line in patients with urinary bladder cancer. The Journal of urology 22 2016797
1988 Antitumor effector mechanism at a distant site in the double grafted tumor system of PSK, a protein-bound polysaccharide preparation. Japanese journal of cancer research : Gann 22 3141330
2010 PSK may suppress CD57(+) T cells to improve survival of advanced gastric cancer patients. International journal of clinical oncology 21 20229169
1993 Stimulation by PSK of interleukin-1 production by human peripheral blood mononuclear cells. Anticancer research 21 8317896
1992 Immunomodulation by orally administered protein-bound polysaccharide PSK in patients with gastrointestinal cancer. Biotherapy (Dordrecht, Netherlands) 21 1622733
1984 Depression of macrophage functions and T-cell-mediated immunity to listeria infection in tumor-bearing mice and its prevention by PSK. Cancer immunology, immunotherapy : CII 21 6334552
2022 A novel type of phytosulfokine, PSK-ε, positively regulates root elongation and formation of lateral roots and root nodules in Medicago truncatula. Plant signaling & behavior 20 36358009
1990 Stimulation of interferon-gamma-induced human myelogenous leukemic cell differentiation by high molecular weight PSK subfraction. Anticancer research 20 2110432
2022 A legume-specific novel type of phytosulfokine, PSK-δ, promotes nodulation by enhancing nodule organogenesis. Journal of experimental botany 19 35137020
2019 Cunninghamia lanceolata PSK Peptide Hormone Genes Promote Primary Root Growth and Adventitious Root Formation. Plants (Basel, Switzerland) 19 31752096
2001 Protective effects of a protein-bound polysaccharide, PSK, on Candida albicans infection in mice via tumor necrosis factor-alpha induction. International immunopharmacology 19 11562071
1999 Protein-bound polysaccharide (PSK) induces cytotoxic activity in the NKL human natural killer cell line. International journal of clinical & laboratory research 19 10784373
1998 The role of neutrophils as cytotoxic cells in lung metastasis: suppression of tumor cell metastasis by a biological response modifier (PSK). In vivo (Athens, Greece) 19 9627799
1992 Tumor cytostasis mediated by LPS- or PSK-activated human plastic-adherent peripheral blood mononuclear cells. Cellular immunology 19 1394447
2011 Protein-bound polysaccharide-K (PSK) induces apoptosis and inhibits proliferation of promyelomonocytic leukemia HL-60 cells. Anticancer research 18 21868514
2002 PSK, a protein-bound polysaccharide, overcomes defective maturation of dendritic cells exposed to tumor-derived factors in vitro. International journal of oncology 18 12011998
2022 TAOK2 rescues autism-linked developmental deficits in a 16p11.2 microdeletion mouse model. Molecular psychiatry 17 36123424
2006 A randomized phase III trial of postoperative adjuvant therapy with S-1 alone versus S-1 plus PSK for stage II/IIIA gastric cancer: Hokuriku-Kinki Immunochemo-Therapy Study Group-Gastric Cancer (HKIT-GC). Japanese journal of clinical oncology 17 16803844
1994 An in vivo study of hepatic and splenic interleukin-1 beta mRNA expression following oral PSK or LEM administration. Japanese journal of cancer research : Gann 16 7852192
1993 Enhancement of T-cell proliferation by PSK. International journal of immunopharmacology 16 8407056
2017 Phase III trial comparing UFT + PSK to UFT + LV in stage IIB, III colorectal cancer (MCSGO-CCTG). Surgery today 15 28634730
2016 Discovery of novel TAOK2 inhibitor scaffolds from high-throughput screening. Bioorganic & medicinal chemistry letters 15 27426302
2012 Polysaccharide-K (PSK) increases p21(WAF/Cip1) and promotes apoptosis in pancreatic cancer cells. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 15 23217280
1996 PSK protects macrophages from lipoperoxide accumulation and foam cell formation caused by oxidatively modified low-density lipoprotein. Atherosclerosis 15 8830930
1988 Production of antiserum against antitumor protein-bound polysaccharide preparation, PSK (Krestin) and its pharmacological application. International journal of immunopharmacology 15 3372106
2012 Protein-bound polysaccharide-K (PSK) induces apoptosis via p38 mitogen-activated protein kinase pathway in promyelomonocytic leukemia HL-60 cells. Anticancer research 14 22753720
2012 Correlation between efficacy of PSK postoperative adjuvant immunochemotherapy for gastric cancer and expression of MHC class I. Experimental and therapeutic medicine 14 22969994
2010 PSK enhances the efficacy of docetaxel in human gastric cancer cells through inhibition of nuclear factor-kappaB activation and survivin expression. International journal of oncology 14 20126979
2009 A protein-bound polysaccharide, PSK, enhances tumor suppression induced by docetaxel in a gastric cancer xenograft model. Anticancer research 14 19414318
2000 Establishment and characterization of a prostatic small-cell carcinoma cell line (PSK-1) derived from a patient with Klinefelter syndrome. The Prostate 14 10679758
1996 Antimetastatic effect of PSK, a protein-bound polysaccharide, against the B16-BL6 mouse melanoma. Invasion & metastasis 14 8830763
2022 A Role for Taok2 in Listeria monocytogenes Vacuolar Escape. The Journal of infectious diseases 13 32582947
2019 Composition of the Reconstituted Cell Wall in Protoplast-Derived Cells of Daucus is Affected by Phytosulfokine (PSK). International journal of molecular sciences 13 31690047
2013 PSK1 regulates expression of SOD1 involved in oxidative stress tolerance in yeast. FEMS microbiology letters 13 24236444
2009 Efficacy of postoperative UFT (Tegafur/Uracil) plus PSK therapies in elderly patients with resected colorectal cancer. Cancer biotherapy & radiopharmaceuticals 13 19243246
1999 Differential effect of protein-bound polysaccharide (PSK) on survival of experimental murine tumors. Journal of experimental & clinical cancer research : CR 13 10374675
1994 Immunochemotherapy in B-16-melanoma-cell-transplanted mice with combinations of interleukin-2, cyclophosphamide, and PSK. Oncology 13 8196915
1988 Morphological and biochemical alterations of macrophages produced by a glycan, PSK. Immunopharmacology 13 3204014
2013 Gamma delta T cells are activated by polysaccharide K (PSK) and contribute to the anti-tumor effect of PSK. Cancer immunology, immunotherapy : CII 12 23685781
2006 Crystal structure of the MAP3K TAO2 kinase domain bound by an inhibitor staurosporine. Acta biochimica et biophysica Sinica 12 16761096
1995 Polysaccharide preparation PSK augments the proliferation and cytotoxicity of tumor-infiltrating lymphocytes in vitro. Anticancer research 12 7762991
1994 Suppression of cancer cell growth in vitro by the protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) with SOD mimicking activity. Cancer biotherapy 12 7812358
1990 Stimulation of human peripheral blood polymorphonuclear cell iodination by PSK subfractions. Anticancer research 12 2369086
1988 Effects of PSK on interleukin-2 production by peripheral lymphocytes of patients with advanced ovarian carcinoma during chemotherapy. Japanese journal of cancer research : Gann 12 3128500
2022 Nuclear speckle integrity and function require TAO2 kinase. Proceedings of the National Academy of Sciences of the United States of America 11 35704758
2008 Protein-bound polysaccharide-K (PSK) directly enhanced IgM production in the human B cell line BALL-1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 11 18848763
1984 Construction of plasmid vectors from Streptomyces kasugaensis plasmids, pSK1 and pSK2. The Journal of antibiotics 11 6094413
2024 The autism susceptibility kinase, TAOK2, phosphorylates eEF2 and modulates translation. Science advances 10 38608030
2007 Enhancement of antitumor effect of tegafur/uracil (UFT) plus leucovorin by combined treatment with protein-bound polysaccharide, PSK, in mouse models. Cellular & molecular immunology 10 17764620
2002 SH2D1A expression reflects activation of T and NK cells in cord blood lymphocytes infected with EBV and treated with the immunomodulator PSK. Immunology letters 10 11803050
1988 PSK, a polysaccharide from Coriolus vesicolor, enhances oxygen metabolism of murine peritoneal macrophages and the host resistance to listerial infection. Journal of general microbiology 10 3141579
2023 The Research Process of PSK Biosynthesis, Signaling Transduction, and Potential Applications in Brassica napus. Plants (Basel, Switzerland) 9 37687322
2017 RETRACTED: Generalized verrucosis and abnormal T cell activation due to homozygous TAOK2 mutation. Journal of dermatological science 9 28385331

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