Affinage

PLK2

Serine/threonine-protein kinase PLK2 · UniProt Q9NYY3

Length
685 aa
Mass
78.2 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 32 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

PLK2 (SNK) is a polo-like serine/threonine kinase that operates in two principal arenas: G1-phase control of the centrosome/cell cycle and activity-dependent homeostatic synaptic plasticity in neurons (PMID:12651910, PMID:10523297, PMID:12972611). Its kinase activity is detectable in G1, depends on the catalytic Lys-108 and the activation residue Thr-236, and is restrained by an autoinhibitory C-terminus and by the calcium/integrin-binding protein CIB (PMID:12651910). PLK2 is transcriptionally induced by p53, and its loss delays S-phase entry and slows proliferation in fibroblasts and embryos, linking it to a p53-dependent cell cycle/mitotic checkpoint program (PMID:12897130, PMID:12972611). Through its polo-box domain PLK2 localizes to the mother centriole in early G1 and to both centrioles at S-phase onset, where it drives centriole duplication by phosphorylating CPAP/SAS-4 and destabilizing the SCF F-box protein Fbxw7 to permit cyclin E accumulation (PMID:20531387, PMID:19001868, PMID:22399798); its abundance at the centrosome is gated by SIRT1-mediated deacetylation and ubiquitin-dependent degradation (PMID:30517871). In neurons, PLK2 is targeted to dendrites following plasticity-inducing stimulation and enforces homeostatic synaptic downscaling by coordinately reprogramming Ras and Rap signaling — phosphorylation-dependent degradation of RasGRF1 and SPAR and activation of SynGAP and PDZGEF1 suppress Ras while activating Rap — and by a kinase-independent, NSF-binding mechanism that disrupts NSF-GluA2 to remove surface AMPARs (PMID:20802490, PMID:21382555, PMID:30049443). PLK2 is the principal kinase phosphorylating alpha-synuclein at Ser-129 in the CNS, recognizing acidic residues flanking the site and engaging the alpha-synuclein N-terminus, and it additionally controls alpha-synuclein handling through autophagy via substrates such as SQSTM1/p62 and DCTN1 (PMID:19004816, PMID:24128992, PMID:22248692, PMID:39316746, PMID:39773002). PLK2 activity is positively set by DYRK1A phosphorylation at Ser-358 and negatively set by CIB binding and SIRT1/SKP1-driven turnover (PMID:30517871, PMID:37387444, PMID:34234930).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1999 Medium

    Established that PLK2 is not a constitutive housekeeping kinase but a stimulus-targeted neuronal protein, showing it is delivered to dendrites of activated neurons during synaptic plasticity and binds CIB through a conserved C-terminal domain.

    Evidence Immunolocalization in stimulated neurons plus yeast two-hybrid/binding assays for CIB

    PMID:10523297

    Open questions at the time
    • Did not define which substrates underlie the dendritic function
    • Functional role of the CIB interaction not resolved
  2. 2003 High

    Defined the biochemical activation logic of PLK2 and a first negative regulator, placing its activity in G1 and identifying CIB as an inhibitor.

    Evidence Site-directed mutagenesis (T236E, K108), in vitro kinase assays, GFP localization to the MTOC, and Co-IP with CIB

    PMID:12651910

    Open questions at the time
    • Physiological MTOC substrates not yet identified
    • Mechanism of C-terminal autoinhibition relief in cells unresolved
  3. 2003 High

    Connected PLK2 to the p53 network and to cell cycle progression, establishing it as a p53 transcriptional target with a mitotic-checkpoint and S-phase entry role.

    Evidence p53 target validation with siRNA knockdown plus paclitaxel/nocodazole death assays; gene-targeted KO mice with BrdU and growth assays

    PMID:12897130 PMID:12972611

    Open questions at the time
    • Direct cell-cycle substrates not identified in these studies
    • Molecular basis of delayed S-phase entry unresolved
  4. 2008 Medium

    Identified the centrosome localization determinant and the first centriole substrate, linking PLK2 polo-box function to procentriole formation.

    Evidence Polo-box mutagenesis and immunofluorescence (centriole localization, PLK4 dependence); in vitro kinase assay and phospho-resistant CPAP mutant

    PMID:19001868 PMID:20531387

    Open questions at the time
    • Hierarchy between PLK2 and PLK4 only partially mapped
    • How CPAP phosphorylation drives elongation mechanistically unresolved
  5. 2008 High

    Established PLK2 as the principal CNS kinase generating Ser-129 phosphorylated alpha-synuclein, the disease-associated modification.

    Evidence In vitro phosphorylation, pharmacological PLK inhibition, shRNA knockdown, and PLK2 KO mice measuring brain pSer-129

    PMID:19004816

    Open questions at the time
    • Consequence of Ser-129 phosphorylation for synuclein aggregation not settled here
    • Identity of residual non-PLK2 kinase activity unknown
  6. 2010 High

    Revealed a kinase-independent PLK2 function in synaptic plasticity, showing PLK2 binds NSF to disrupt NSF-GluA2 and remove surface AMPARs.

    Evidence Reciprocal Co-IP, surface receptor and electrophysiology assays in rat hippocampal neurons, domain-mapping mutagenesis

    PMID:20802490

    Open questions at the time
    • Structural basis of the non-polo-box NSF-binding motif undefined
    • How kinase-dependent and kinase-independent PLK2 activities are coordinated unresolved
  7. 2011 High

    Defined the mechanism by which PLK2 enforces homeostatic synaptic downscaling through coordinated Ras-suppression and Rap-activation, and linked this to memory.

    Evidence Genetic epistasis, phosphorylation and ubiquitin-proteasome assays on RasGRF1, SPAR, SynGAP, PDZGEF1; spine imaging and behavioral memory tasks

    PMID:21382555

    Open questions at the time
    • Phosphosites on each GTPase regulator not all mapped here
    • Whether all four substrates are phosphorylated in the same synapse unresolved
  8. 2011 Medium

    Extended PLK2 into oncogenic p53 biology, showing it phosphorylates mutant p53 to potentiate its transcriptional activity in an autoregulatory loop.

    Evidence Co-IP, kinase assay, transcriptional reporter assays, siRNA knockdown

    PMID:22134238

    Open questions at the time
    • Phosphosite on mutant p53 not defined
    • In vivo relevance to tumor phenotypes untested here
  9. 2012 High

    Expanded the centriole-duplication mechanism by showing PLK2 destabilizes Fbxw7 to drive cyclin E accumulation, and quantitatively defined PLK2 reshaping of SynGAP GTPase selectivity.

    Evidence In vitro kinase assays with phosphosite mapping (Fbxw7 S176; SynGAP by MS), Co-IP, GTPase activity measurements, centriole counting

    PMID:22399798 PMID:30049443

    Open questions at the time
    • Whether Fbxw7 destabilization contributes to centriole amplification in vivo unresolved
    • Integration of PLK2 and CDK5 SynGAP phosphorylation in intact synapses not tested
  10. 2012 Medium

    Defined the substrate-recognition determinants of PLK2 on alpha-synuclein and broadened its in vitro substrate repertoire.

    Evidence In vitro kinase assays with peptide substitution (Glu-126/Glu-131), comparison with CK2; cell-lysate kinase assay with MS phosphosite mapping (HSP90, GRP-94, beta-tubulin, calumenin, 14-3-3 epsilon); yeast Cdc5/Rho1 genetics

    PMID:22248692 PMID:22828320 PMID:22988096

    Open questions at the time
    • In-cell relevance of the broad in vitro substrate set unverified
    • Functional consequence of HSP90/tubulin/14-3-3 phosphorylation unknown
  11. 2013 High

    Pharmacologically and structurally validated PLK2 as the dominant in vivo Ser-129 alpha-synuclein kinase, enabling selective inhibitor development.

    Evidence PLK2-inhibitor crystal structures with kinome selectivity and in vivo rat brain pharmacodynamics; KO/heterozygote dosage study with BI 2536 epistasis

    PMID:23794260 PMID:24128992

    Open questions at the time
    • Identity of the residual non-PLK2 Ser-129 kinase unresolved
    • Therapeutic consequence of reducing pSer-129 not established here
  12. 2014 Medium

    Demonstrated an in vivo tissue-morphogenesis role, showing Plk2 controls mitotic spindle orientation and epithelial polarity in the mammary gland.

    Evidence Plk2 KO mice with spindle orientation imaging and mammary morphology/proliferation analysis

    PMID:24598160

    Open questions at the time
    • Spindle-orientation substrate not identified
    • Mechanistic link to centriole substrates unresolved
  13. 2015 Medium

    Positioned PLK2 within centrosome-amplification and tumor-suppressor signaling pathways through NPM/ROCK2/PLK4 and TAp73 phosphorylation.

    Evidence Centrosome amplification epistasis/rescue assays; in vitro kinase assay and Co-IP for TAp73 S48 with cisplatin functional assays

    PMID:25590559 PMID:26625870

    Open questions at the time
    • Direct NPM phosphosite and ROCK2 activation mechanism partly unresolved
    • TAp73 axis tested in limited cell contexts
  14. 2017 Medium

    Linked PLK2 to alpha-synuclein clearance, showing PLK2 promotes macroautophagic co-degradation of phospho-synuclein and itself.

    Evidence Genetic/pharmacological autophagy inhibition, domain mapping, ubiquitination assays, Co-IP

    PMID:28154193

    Open questions at the time
    • Autophagy receptor mediating PLK2/synuclein clearance not defined here
    • Reconciliation with later flux-blocking role unresolved
  15. 2018 High

    Defined the cell-cycle-timed PTM circuit controlling PLK2 abundance, with AURKA-phosphorylated SIRT1 deacetylating PLK2 to license its ubiquitin-dependent turnover and centrosomal accumulation.

    Evidence Co-IP, acetylation/ubiquitination/deacetylase assays, cell-cycle synchronization, centrosome imaging

    PMID:30517871

    Open questions at the time
    • E3 ligase acting on deacetylated PLK2 not identified
    • Acetylated lysines on PLK2 not fully mapped
  16. 2021 Medium

    Identified SKP1-mediated ubiquitination as an additional route of PLK2 degradation relevant to alpha-synuclein aggregation.

    Evidence Co-IP, in vitro ubiquitination assay, miRNA target luciferase reporter

    PMID:34234930

    Open questions at the time
    • Single lab with modest methodological depth; not independently confirmed
    • Relationship to SIRT1-dependent turnover pathway unresolved
  17. 2023 Medium

    Identified DYRK1A as a positive upstream activator of PLK2 (Ser-358 phosphorylation increasing stability and activity) and added N-cadherin as a synaptic substrate, broadening upstream control and downstream effects.

    Evidence Co-IP and in vitro kinase assays with phosphosite mutagenesis; N-cadherin kinase/Co-IP and proteolytic processing assays with synaptic imaging

    PMID:37387444 PMID:37654026

    Open questions at the time
    • Whether DYRK1A control operates in neurons as well as cancer cells untested
    • N-cadherin axis from a single lab
  18. 2024 Medium

    Expanded PLK2 into proteostasis and stress-protection roles via SQSTM1/p62 S349, GSK3beta inactivation, and KLF5-driven transcription, connecting PLK2 to aggrephagy, antioxidant signaling, and autophagy suppression.

    Evidence In vitro kinase assays with phosphosite mutagenesis, Co-IP, aggregate-formation assays; gain/loss-of-function with GSK3beta/HO-1/ROS readouts in two organ-injury models; ChIP-qPCR and luciferase for KLF5

    PMID:35523306 PMID:39316746 PMID:39563073 PMID:41198759

    Open questions at the time
    • GSK3beta and KLF5 axes are largely single-context
    • How aggrephagy-promoting and flux-blocking roles coexist unresolved
  19. 2025 High

    Revealed a kinase-dependent but Ser-129-independent mechanism by which PLK2 drives synuclein pathology, phosphorylating DCTN1 (S1098) to block autophagosome-lysosome fusion and impair flux.

    Evidence In vitro kinase assay with phosphosite ID, autophagy flux/fusion imaging (LC3, LAMP1), in vivo mouse model with genetic PLK2 suppression

    PMID:39773002

    Open questions at the time
    • How the same kinase both clears (macroautophagy) and blocks (flux) synuclein not reconciled
    • Whether DCTN1 phosphorylation occurs in human disease tissue untested
  20. 2026 Medium

    Placed PLK2 within a FAM117B/DYRK1A signaling axis promoting colorectal cancer phenotypes, extending the DYRK1A-PLK2 regulatory module to a new tumor context.

    Evidence Co-IP, IP-kinase assay, knockdown/overexpression rescue, in vivo xenograft

    PMID:41504297

    Open questions at the time
    • Direct PLK2 substrates driving CRC phenotypes not identified
    • Single-lab cancer-context finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PLK2's distinct functional modes — kinase-dependent centriole/synaptic substrate phosphorylation, kinase-independent NSF disruption, and opposing pro- and anti-autophagic actions on alpha-synuclein — are selected within a single cell remains unresolved.
  • No unified model integrating cell-cycle versus synaptic substrate selection
  • No structural basis distinguishing polo-box-dependent versus NSF-binding modes
  • Reconciliation of synuclein clearance versus flux-blocking roles missing

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016740 transferase activity 5 GO:0098772 molecular function regulator activity 2 GO:0140657 ATP-dependent activity 1
Localization
GO:0005815 microtubule organizing center 3 GO:0005856 cytoskeleton 1
Pathway
R-HSA-1640170 Cell Cycle 5 R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 4 R-HSA-9612973 Autophagy 4 R-HSA-1852241 Organelle biogenesis and maintenance 3
Partners
CIB1DYRK1AFBXW7NPM1NSFSIRT1SKP1TSC1

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 PLK2/Snk is a direct transcriptional target of p53; its kinase activity is negatively regulated by its C-terminus, and siRNA-mediated silencing in the presence of paclitaxel or nocodazole significantly increased apoptosis occurring in mitotic cells, indicating a p53-dependent mitotic checkpoint role. siRNA knockdown, mutagenesis, cell death assays in mitotic cells Molecular and cellular biology Medium 12897130
2003 Endogenous Snk/PLK2 kinase activity is detected in G1 phase; substitution of Thr-236 with glutamate increases kinase activity ~10-fold while Lys-108 substitution abolishes activity; GFP-C-Snk localizes to the microtubule organizing center in a polo-box-dependent manner; calcium- and integrin-binding protein CIB co-immunoprecipitates with Snk and inhibits its kinase activity, functioning as a negative regulator. Site-directed mutagenesis, kinase assays, GFP localization, Co-immunoprecipitation, in vitro kinase inhibition assay Molecular cancer research : MCR High 12651910
1999 Snk/PLK2 protein is targeted to dendrites of activated neurons following stimuli that produce synaptic plasticity (including LTP); a conserved C-terminal domain of Snk interacts specifically with CIB (Ca2+- and integrin-binding protein). Immunolocalization in neurons, yeast two-hybrid and binding assays for CIB interaction The EMBO journal Medium 10523297
2003 Plk2-deficient mouse embryonic fibroblasts grow more slowly and show delayed entry into S phase; Plk2-null embryos show retarded growth and decreased cell proliferation in the labyrinthine zone of the placenta, establishing a role for Plk2 in cell cycle progression. Gene-targeted knockout mice, BrdU incorporation, cell growth assays Molecular and cellular biology High 12972611
2008 PLK2 directly phosphorylates alpha-synuclein at Ser-129 in vitro; PLK kinase inhibitors reduced pSer-129 alpha-synuclein in primary cortical cultures and mouse brain in vivo; specific shRNA knockdown or knockout of Plk2 reduced pSer-129 levels, establishing PLK2 as a principal kinase for this modification in the CNS. In vitro biochemical phosphorylation assay, pharmacological inhibition, shRNA knockdown, PLK2 knockout mice The Journal of biological chemistry High 19004816
2010 PLK2 directly phosphorylates CPAP (centrosomal P4.1-associated protein, human SAS-4 homologue) at S589 and S595 in vitro and in vivo; this phosphorylation is critical for procentriole formation during the centrosome cycle; phospho-resistant CPAP mutant fails to form elongated centrioles. In vitro kinase assay, phospho-site mutagenesis, cell cycle stage-specific phosphorylation analysis, overexpression of phospho-resistant mutant The EMBO journal High 20531387
2008 The polo-box domain of PLK2 is required for its centrosomal localization; mutation of critical polo-box residues prevents centrosomal localization and impairs centriole duplication; PLK2 localizes exclusively to the mother centriole in early G1 then distributes to both centrioles at S phase onset; PLK2-mediated centriole duplication depends on PLK4 function. Polo-box mutagenesis, immunofluorescence localization, siRNA knockdown, spindle analysis Cell cycle (Georgetown, Tex.) Medium 19001868
2010 PLK2 directly interacts with NSF (N-ethylmaleimide-sensitive fusion protein) and disrupts the NSF-GluA2 interaction, promoting loss of surface GluA2 AMPAR subunit, greater association of GluA2 with PICK1 and GRIP1, and decreased synaptic AMPAR current; this effect requires PLK2-NSF engagement but not PLK2 kinase activity, and occurs through a motif in PLK2 independent of canonical polo-box sites. Co-immunoprecipitation, surface receptor assays, electrophysiology in rat hippocampal neurons, domain-mapping mutagenesis Nature neuroscience High 20802490
2011 Plk2 directs phosphorylation-dependent ubiquitin-proteasome degradation of RasGRF1 (Ras activator) and SPAR (Rap inhibitor), and phosphorylation-dependent stimulation of SynGAP (Ras inhibitor) and PDZGEF1 (Rap activator); collectively these actions suppress Ras and activate Rap signaling; perturbation of Plk2 prevents homeostatic shrinkage and loss of dendritic spines and impairs memory formation. Genetic epistasis, phosphorylation assays, ubiquitin-proteasome pathway assays, dendritic spine imaging, behavioral memory tasks Neuron High 21382555
2012 Plk2 directly phosphorylates Fbxw7 (human Cdc4/SCF ubiquitin ligase F-box protein) at serine 176; this phosphorylation destabilizes Fbxw7, leading to cyclin E accumulation and increased centriole duplication potential; the two proteins form a complex in vitro and in vivo. In vitro kinase assay, Co-immunoprecipitation, phospho-site mutagenesis, centriole counting assays Journal of cell science High 22399798
2009 PLK2 interacts with endogenous TSC1 protein; a C-terminal PLK2-GST fusion protein binds both TSC1 and TSC2; cells overexpressing PLK2 show decreased phosphorylation of p70S6K (downstream mTOR target) during hypoxia, indicating PLK2 modulates mTOR signaling via TSC1/2 interaction. Co-immunoprecipitation, GST pulldown, p70S6K phosphorylation assay, tumor xenografts Cell cycle (Georgetown, Tex.) Medium 20054236
2011 PLK2 binds to and phosphorylates mutant p53, potentiating its oncogenic transcriptional activity; phosphorylated mutant p53 binds more efficiently to p300; Plk2 gene is transcriptionally regulated by both wild-type and mutant p53, forming an autoregulatory feedback loop. Co-immunoprecipitation, kinase assay, transcriptional reporter assays, siRNA knockdown Cell cycle (Georgetown, Tex.) Medium 22134238
2012 PLK2 phosphorylates synGAP, shifting the ratio of synGAP GAP activity toward greater inactivation of HRas (65% increase) relative to Rap1 (16% increase); simultaneous phosphorylation by Plk2 and CDK5 at distinct sites produces additive increase in HRas GAP activity (~230%) and also increases GAP activity toward Rap2. In vitro kinase assay with recombinant synGAP, GTPase activity measurements, mass spectrometry identification of phosphosites Biochemical and biophysical research communications High 30049443
2013 PLK2 genetic knockout in mouse brain produces a gene-dosage-dependent reduction of endogenous Ser129-phosphorylated alpha-synuclein in all brain regions examined; pharmacological inhibition with pan-PLK inhibitor BI 2536 did not further reduce residual pSer-129 in PLK2 KO mice, indicating PLK2 is the primary but not sole kinase for this modification in vivo. PLK2 knockout mice, heterozygous mice, pharmacological inhibition with BI 2536, brain regional pSer-129 alpha-synuclein quantification Neuroscience High 24128992
2012 Alpha-synuclein is a substrate of yeast Cdc5 (PLK2 ortholog) and human PLK2; elevated levels of alpha-synuclein prevent Cdc5/Plk2 from maintaining normal GTP-bound Rho1 levels, disrupting MAPK stress signaling; the nine N-terminal amino acids of alpha-synuclein are essential for the interaction with polo-like kinases. Yeast genetics and biochemistry, GTP-Rho1 pull-down assay, N-terminal deletion mutagenesis of alpha-synuclein Proceedings of the National Academy of Sciences of the United States of America Medium 22988096
2012 PLK2 is superior to CK2 as a catalyst of alpha-synuclein Ser-129 phosphorylation; acidic residues at positions n-3 (Glu-126) and n+2 (Glu-131) flanking Ser-129 are critical determinants for phosphorylation by PLK2, as their replacement with alanine abrogates phosphorylation. In vitro kinase assay with full-length alpha-synuclein and substituted peptides, comparison with CK2 Biochemical and biophysical research communications High 22248692
2017 PLK2 phosphorylates alpha-synuclein and promotes its selective degradation via macroautophagy; PLK2 and alpha-synuclein undergo co-degradation; the N-terminal region of alpha-synuclein is important for PLK2-mediated phosphorylation and physical interaction; PLK2 polyubiquitination is important for the PLK2-alpha-syn complex degradation by the macroautophagy machinery. Pharmacological and genetic inhibition of macroautophagy, domain mutagenesis, ubiquitination assays, Co-immunoprecipitation The Journal of biological chemistry Medium 28154193
2015 PLK2 directly phosphorylates TAp73 at Ser48 within the TA domain; phosphorylation is abolished by Ser48→Ala mutation; PLK2 physically binds TAp73; PLK2 inhibition combined with cisplatin leads to increased p21 and PUMA expression, cell cycle G1 arrest, increased apoptosis, and decreased invasion in TAp73-enriched osteosarcoma cells, effects absent in TAp73 knockdown cells. In vitro kinase assay, Co-immunoprecipitation, site-directed mutagenesis, siRNA knockdown, cell biology assays Cancer medicine Medium 26625870
2007 PLK2 interacts with Chk2, Chk1, Ser317-phosphorylated Chk1, and p53 (by Co-immunoprecipitation); Plk2-deficient cells show higher H2AX Ser139 phosphorylation (indicating more DNA damage) and reduced Ser317-phosphorylated Chk1 under replication stress, indicating PLK2 contributes to S-phase checkpoint activation. Co-immunoprecipitation, siRNA knockdown, phospho-specific western blotting, cell death assays with aphidicolin/etoposide Cell cycle (Georgetown, Tex.) Medium 17912033
2018 SIRT1 deacetylates Plk2; acetylation of Plk2 protects it from ubiquitination, while SIRT1-mediated deacetylation promotes ubiquitin-dependent Plk2 degradation; AURKA phosphorylates SIRT1 and promotes the SIRT1-Plk2 interaction during mitosis; in early-mid G1 phosphorylated SIRT1 deacetylates and degrades Plk2, while in late G1 hypophosphorylated SIRT1 has reduced Plk2 affinity allowing Plk2 accumulation at centrosomes for centriole duplication. Co-immunoprecipitation, acetylation/ubiquitination assays, deacetylase assay, cell cycle synchronization, centrosome imaging Cell reports High 30517871
2015 PLK2 indirectly activates ROCK2 via phosphorylating nucleophosmin (NPM); PLK4 functions downstream of ROCK2 to drive centrosome amplification; epistasis rescue assay placed PLK2 upstream of ROCK2 upstream of PLK4 in a linear centrosome amplification pathway. Centrosome amplification rescue assay, siRNA knockdown epistasis, kinase activity assays Cell cycle (Georgetown, Tex.) Medium 25590559
2014 Plk2 regulates mitotic spindle orientation in mammary gland epithelium; loss of Plk2 leads to increased mammary epithelial cell proliferation, ductal hyperbranching, and loss of proper cell polarity, defining a role for Plk2 in spindle orientation and mammary gland development in vivo. Plk2 knockout mice, spindle orientation imaging, mammary gland morphology analysis, proliferation assays Development (Cambridge, England) Medium 24598160
2023 DYRK1A interacts with and phosphorylates PLK2 at Ser358; this phosphorylation increases PLK2 protein stability and markedly induces PLK2 kinase activity (evidenced by upregulation of alpha-synuclein S129 phosphorylation); DYRK1A-mediated PLK2 phosphorylation contributes to GBM cell proliferation, migration, and invasion. Co-immunoprecipitation, in vitro kinase assay, phospho-site mutagenesis, cell biology assays International journal of oncology Medium 37387444
2024 PLK2 phosphorylates SQSTM1/p62 at S349 following proteasome inhibition; this phosphorylation strengthens SQSTM1 binding to KEAP1, required for formation of large SQSTM1 aggregates/bodies; PLK2 is upregulated upon proteasome inhibition and associates with SQSTM1. Co-immunoprecipitation, in vitro kinase assay, phospho-site mutagenesis, aggregate formation assays, proteasome inhibition experiments Autophagy High 39316746
2025 PLK2 phosphorylates DCTN1 (dynactin 1) at S1098, impairing autophagosome-lysosome fusion and blocking autophagic flux; PLK2 overexpression promotes SNCA/alpha-synuclein PFF-induced aggregation (including of phosphorylation-resistant SNCAS129A) and neurotoxicity independently of S129 phosphorylation; genetic or pharmacological PLK2 inhibition reduced SNCA deposition and motor dysfunction in vivo. In vitro kinase assay, phospho-site identification, autophagy flux assays (LC3, LAMP1), autophagosome-lysosome fusion imaging, in vivo mouse model with genetic PLK2 suppression Autophagy High 39773002
2023 Plk2 directly phosphorylates N-cadherin and promotes its proteolytic processing and degradation during neuronal hyperexcitation; Plk2 also disrupts N-cadherin complexes with APP; loss of N-cadherin adhesive function destabilizes excitatory synapses as part of homeostatic synaptic plasticity. In vitro kinase assay, Co-immunoprecipitation, proteolytic processing assays, synaptic imaging in neurons Journal of neurochemistry Medium 37654026
2021 SKP1 directly interacts with PLK2 (by co-immunoprecipitation) and promotes PLK2 ubiquitination and protein degradation (by in vitro ubiquitination assay); reduced PLK2 due to SKP1-mediated degradation contributes to alpha-synuclein aggregation in neurons. Co-immunoprecipitation, in vitro ubiquitination assay, luciferase reporter for miRNA target validation Journal of healthcare engineering Medium 34234930
2026 FAM117B interacts with DYRK1A and acts as its upstream regulator; DYRK1A induces PLK2 phosphorylation in colorectal cancer cells, thereby upregulating PLK2 protein expression; the FAM117B/DYRK1A/PLK2 axis promotes CRC cell proliferation, migration, and invasion. Co-immunoprecipitation, immunoprecipitation-kinase assay, knockdown/overexpression rescue experiments, in vivo xenograft model Cell biology international Medium 41504297
2024 PLK2 phosphorylates GSK3β, increasing its phosphorylation (inactivation); PLK2 overexpression reduces oxidative stress and apoptosis in cisplatin-treated renal cells and hepatic I/R models via increased GSK3β phosphorylation and downstream HO-1 antioxidant enzyme expression. PLK2 overexpression/siRNA knockdown, GSK3β phosphorylation western blotting, HO-1 expression assays, ROS measurement, in vivo AKI/I-R mouse models Experimental cell research / Journal of gastroenterology and hepatology Medium 35523306 39563073
2013 Structure-guided crystallography of PLK2-inhibitor complexes enabled design of brain-penetrant, isoform-selective PLK2 inhibitors; oral administration of lead compounds significantly decreased Ser129 alpha-synuclein phosphorylation in rat brain, pharmacologically validating PLK2 as the dominant kinase for this modification in vivo. Crystal structure of PLK2-inhibitor complex, kinome selectivity profiling, in vivo rat brain pharmacodynamics ChemMedChem High 23794260
2012 PLK2 phosphorylates HSP90, GRP-94, beta-tubulin, calumenin, and 14-3-3 epsilon in vitro; mass spectrometry identified the specific phosphosites generated by PLK2 on these substrates, revealing PLK2 substrate specificity determinants. Cell lysate kinase assay, 2D gel electrophoresis, mass spectrometry phosphosite identification Biochimica et biophysica acta Medium 22828320
2025 KLF5 transcription factor directly binds to the PLK2 promoter (by ChIP-qPCR and dual-luciferase reporter assay) and transcriptionally activates PLK2 expression; elevated PLK2 inhibits chondrocyte autophagy and contributes to osteoarthritis progression. ChIP-qPCR, dual-luciferase reporter assay, PLK2 knockdown, autophagy markers (Beclin-1, LC3), OA mouse model Scientific reports Medium 41198759

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Silencing of the novel p53 target gene Snk/Plk2 leads to mitotic catastrophe in paclitaxel (taxol)-exposed cells. Molecular and cellular biology 198 12897130
2008 Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The Journal of biological chemistry 193 19004816
1999 The polo-like protein kinases Fnk and Snk associate with a Ca(2+)- and integrin-binding protein and are regulated dynamically with synaptic plasticity. The EMBO journal 176 10523297
2003 Role of Plk2 (Snk) in mouse development and cell proliferation. Molecular and cellular biology 133 12972611
2005 Transcriptional silencing of Polo-like kinase 2 (SNK/PLK2) is a frequent event in B-cell malignancies. Blood 106 16160013
2011 Requirement for Plk2 in orchestrated ras and rap signaling, homeostatic structural plasticity, and memory. Neuron 83 21382555
2003 The serum-inducible protein kinase Snk is a G1 phase polo-like kinase that is inhibited by the calcium- and integrin-binding protein CIB. Molecular cancer research : MCR 69 12651910
2016 Plk2 promotes tumor growth and inhibits apoptosis by targeting Fbxw7/Cyclin E in colorectal cancer. Cancer letters 68 27423313
2018 Lead, cadmium, arsenic, and mercury combined exposure disrupted synaptic homeostasis through activating the Snk-SPAR pathway. Ecotoxicology and environmental safety 65 30099283
2012 Plk2 regulates centriole duplication through phosphorylation-mediated degradation of Fbxw7 (human Cdc4). Journal of cell science 63 22399798
2006 Evaluation of Rana snk esculenta blood cell response to chemical stressors in the environment during the larval and adult phases. Aquatic toxicology (Amsterdam, Netherlands) 63 17150265
2014 MicroRNA-27a promotes proliferation and suppresses apoptosis by targeting PLK2 in laryngeal carcinoma. BMC cancer 62 25239093
2011 Mutant p53 oncogenic functions are sustained by Plk2 kinase through an autoregulatory feedback loop. Cell cycle (Georgetown, Tex.) 61 22134238
2010 Plk2 attachment to NSF induces homeostatic removal of GluA2 during chronic overexcitation. Nature neuroscience 60 20802490
2010 PLK2 phosphorylation is critical for CPAP function in procentriole formation during the centrosome cycle. The EMBO journal 57 20531387
2009 The p53 target Plk2 interacts with TSC proteins impacting mTOR signaling, tumor growth and chemosensitivity under hypoxic conditions. Cell cycle (Georgetown, Tex.) 56 20054236
2012 Celastrol suppresses breast cancer MCF-7 cell viability via the AMP-activated protein kinase (AMPK)-induced p53-polo like kinase 2 (PLK-2) pathway. Cellular signalling 54 23266469
2007 Replication stress, defective S-phase checkpoint and increased death in Plk2-deficient human cancer cells. Cell cycle (Georgetown, Tex.) 53 17912033
2008 Plk2 regulated centriole duplication is dependent on its localization to the centrioles and a functional polo-box domain. Cell cycle (Georgetown, Tex.) 52 19001868
2011 Polo-like kinase Plk2 is an epigenetic determinant of chemosensitivity and clinical outcomes in ovarian cancer. Cancer research 47 21402713
2019 Neuroprotective effects of protocatechuic aldehyde through PLK2/p-GSK3β/Nrf2 signaling pathway in both in vivo and in vitro models of Parkinson's disease. Aging 44 31697645
2013 In vivo modulation of polo-like kinases supports a key role for PLK2 in Ser129 α-synuclein phosphorylation in mouse brain. Neuroscience 44 24128992
2014 Mir-126 inhibits growth of SGC-7901 cells by synergistically targeting the oncogenes PI3KR2 and Crk, and the tumor suppressor PLK2. International journal of oncology 41 24969300
2012 α-Synuclein disrupts stress signaling by inhibiting polo-like kinase Cdc5/Plk2. Proceedings of the National Academy of Sciences of the United States of America 36 22988096
2013 Selective and brain-permeable polo-like kinase-2 (Plk-2) inhibitors that reduce α-synuclein phosphorylation in rat brain. ChemMedChem 35 23794260
2011 Polo-like kinase 2 (SNK/PLK2) is a novel epigenetically regulated gene in acute myeloid leukemia and myelodysplastic syndromes: genetic and epigenetic interactions. Annals of hematology 34 21340720
2012 Investigation on PLK2 and PLK3 substrate recognition. Biochimica et biophysica acta 31 22828320
2017 Dissecting the Molecular Pathway Involved in PLK2 Kinase-mediated α-Synuclein-selective Autophagic Degradation. The Journal of biological chemistry 30 28154193
2014 Plk2 regulates mitotic spindle orientation and mammary gland development. Development (Cambridge, England) 30 24598160
2020 Loss of PLK2 induces acquired resistance to temozolomide in GBM via activation of notch signaling. Journal of experimental & clinical cancer research : CR 29 33176854
2009 Identification of urine PLK2 as a marker of bladder tumors by proteomic analysis. World journal of urology 27 19506885
2022 Lactobacillus salivarius SNK-6 Regulates Liver Lipid Metabolism Partly via the miR-130a-5p/MBOAT2 Pathway in a NAFLD Model of Laying Hens. Cells 26 36552896
2019 Nrf2-lncRNA controls cell fate by modulating p53-dependent Nrf2 activation as an miRNA sponge for Plk2 and p21cip1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26 30897343
2018 Histone Deacetylase SIRT1 Targets Plk2 to Regulate Centriole Duplication. Cell reports 26 30517871
2017 PLK2 Plays an Essential Role in High D-Glucose-Induced Apoptosis, ROS Generation and Inflammation in Podocytes. Scientific reports 26 28655909
2012 Superiority of PLK-2 as α-synuclein phosphorylating agent relies on unique specificity determinants. Biochemical and biophysical research communications 25 22248692
2013 Design and synthesis of highly selective, orally active Polo-like kinase-2 (Plk-2) inhibitors. Bioorganic & medicinal chemistry letters 23 23522834
2001 Identification of the human homologue of the early-growth response gene Snk, encoding a serum-inducible kinase. DNA sequence : the journal of DNA sequencing and mapping 23 11696980
2012 Hormonal induction of polo-like kinases (Plks) and impact of Plk2 on cell cycle progression in the rat ovary. PloS one 21 22870256
2018 Plk2 Loss Commonly Occurs in Colorectal Carcinomas but not Adenomas: Relationship to mTOR Signaling. Neoplasia (New York, N.Y.) 18 29448085
2013 Prenatal stress increased Snk Polo-like kinase 2, SCF β-TrCP ubiquitin ligase and ubiquitination of SPAR in the hippocampus of the offspring at adulthood. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 18 23850969
2007 Involvement of the Snk-SPAR pathway in glutamate-induced excitotoxicity in cultured hippocampal neurons. Brain research 18 17706945
2019 Plk2 Regulated by miR-128 Induces Ischemia-Reperfusion Injury in Cardiac Cells. Molecular therapy. Nucleic acids 17 31902745
2017 Microwave radiation leading to shrinkage of dendritic spines in hippocampal neurons mediated by SNK-SPAR pathway. Brain research 17 29180226
2022 Lactobacillus salivarius SNK-6 Activates Intestinal Mucosal Immune System by Regulating Cecal Microbial Community Structure in Laying Hens. Microorganisms 16 35889188
2021 PLK2 protects retinal ganglion cells from oxidative stress by potentiating Nrf2 signaling via GSK-3β. Journal of biochemical and molecular toxicology 16 34047419
2021 Tumor suppressor PLK2 may serve as a biomarker in triple-negative breast cancer for improved response to PLK1 therapeutics. Cancer research communications 16 35156101
2015 Discovery of 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one (7ao) as a potent selective inhibitor of Polo like kinase 2 (PLK2). Bioorganic & medicinal chemistry 16 26762835
2023 Effect of Lactobacillus salivarius SNK-6 on egg quality, intestinal morphology, and cecal microbial community of laying hens. Poultry science 15 37980753
2018 The Acidophilic Kinases PLK2 and PLK3: Structure, Substrate Targeting and Inhibition. Current protein & peptide science 15 29366414
2015 PLK2 phosphorylates and inhibits enriched TAp73 in human osteosarcoma cells. Cancer medicine 14 26625870
2004 Erythrocytic sorbitol contents in diabetic patients correlate with blood aldose reductase protein contents and plasma glucose levels, and are normalized by the potent aldose reductase inhibitor fidarestat (SNK-860). Journal of diabetes and its complications 14 15531183
2018 Phosphorylation of synaptic GTPase-activating protein (synGAP) by polo-like kinase (Plk2) alters the ratio of its GAP activity toward HRas, Rap1 and Rap2 GTPases. Biochemical and biophysical research communications 13 30049443
2020 LY354740 Reduces Extracellular Glutamate Concentration, Inhibits Phosphorylation of Fyn/NMDARs, and Expression of PLK2/pS129 α-Synuclein in Mice Treated With Acute or Sub-Acute MPTP. Frontiers in pharmacology 12 32180729
2011 Plk2 Raps up Ras to subdue synapses. Small GTPases 12 21776418
2023 DYRK1A-mediated PLK2 phosphorylation regulates the proliferation and invasion of glioblastoma cells. International journal of oncology 11 37387444
2023 Isolation and Proteomic Analysis of Extracellular Vesicles from Lactobacillus salivarius SNK-6. Journal of microbiology and biotechnology 11 38282412
2022 Inhibition of PLK2 activity affects APP and tau pathology and improves synaptic content in a sex-dependent manner in a 3xTg mouse model of Alzheimer's disease. Neurobiology of disease 11 35905928
2020 Targeting Adaptive IRE1α Signaling and PLK2 in Multiple Myeloma: Possible Anti-Tumor Mechanisms of KIRA8 and Nilotinib. International journal of molecular sciences 11 32878237
2019 Downregulated miR-27b promotes keratinocyte proliferation by targeting PLK2 in oral lichen planus. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 11 30638284
2016 Complicated function of dopamine in Aβ-related neurotoxicity: Dual interactions with Tyr10 and SNK(26-28) of Aβ. Journal of inorganic biochemistry 11 27687332
2010 Role of the SNK-SPAR pathway in the development of Alzheimer's disease. IUBMB life 11 20146300
2008 Effects of Zibu Piyin recipe on SNK-SPAR pathway in neuron injury induced by glutamate. Chinese journal of integrative medicine 11 18679602
2015 Functional relationship among PLK2, PLK4 and ROCK2 to induce centrosome amplification. Cell cycle (Georgetown, Tex.) 10 25590559
2013 Pharmacological inhibition of polo like kinase 2 (PLK2) does not cause chromosomal damage or result in the formation of micronuclei. Toxicology and applied pharmacology 10 23466428
2012 Tools to discriminate between targets of CK2 vs PLK2/PLK3 acidophilic kinases. BioTechniques 10 26307252
2021 Circular RNA 0102049 suppresses the progression of osteosarcoma through modulating miR-520g-3p/PLK2 axis. Bioengineered 9 34060415
2017 Inhibition of SNK-SPAR signaling pathway promotes the restoration of motor function in a rat model of ischemic stroke. Journal of cellular biochemistry 9 28696012
2022 PLK2 targets GSK3β to protect against cisplatin-induced acute kidney injury. Experimental cell research 8 35523306
2021 miR-101-3p Contributes to α-Synuclein Aggregation in Neural Cells through the miR-101-3p/SKP1/PLK2 Pathway. Journal of healthcare engineering 8 34234930
2021 Systemic mesalazine treatment prevents spontaneous skin fibrosis in PLK2-deficient mice. Naunyn-Schmiedeberg's archives of pharmacology 8 34410453
1999 Inhibitory effect of orally administered aldose reductase inhibitor SNK-860 on corneal polyol accumulation in galactose-fed rats. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 8 10447652
1995 Effects of glucose and SNK-860, an aldose reductase inhibitor, on the polyol pathway and chemiluminescence response of human neutrophils in vitro. Diabetic medicine : a journal of the British Diabetic Association 8 7648800
2014 Identification of the PLK2-dependent phosphopeptidome by quantitative proteomics [corrected]. PloS one 7 25338102
2011 Repeated carbenoxolone injections during late pregnancy alter Snk-SPAR and PSD-95 expression in the hippocampus of rat pups. Neuroscience letters 7 21362453
2025 Supercharged Natural Killer (sNK) Cells Inhibit Melanoma Tumor Progression and Restore Endogenous NK Cell Function in Humanized BLT Mice. Cancers 6 40805135
2024 PLK2-mediated phosphorylation of SQSTM1 S349 promotes aggregation of polyubiquitinated proteins upon proteasomal dysfunction. Autophagy 6 39316746
2017 Role of norepinephrine in Aβ-related neurotoxicity: dual interactions with Tyr10 and SNK(26-28) of Aβ. Acta biochimica et biophysica Sinica 6 28069584
2017 The SNK and SPAR signaling pathway changes in hippocampal neurons treated with amyloid-beta peptide in vitro. Neuropeptides 6 28400058
2011 Response of renal parenchyma and interstitium of Rana snk. esculenta to environmental pollution. Ecotoxicology and environmental safety 6 21497903
2020 Proteome Analysis in a Mammalian Cell line Reveals that PLK2 is Involved in Avian Metapneumovirus Type C (aMPV/C)-Induced Apoptosis. Viruses 5 32231136
2025 PLK2 disrupts autophagic flux to promote SNCA/α-synuclein pathology. Autophagy 4 39773002
2024 The protective effects of Lactobacillus SNK-6 on growth, organ health, and intestinal function in geese exposed to low concentration Aflatoxin B1. Poultry science 4 38880050
2023 Plk2 promotes synaptic destabilization through disruption of N-cadherin adhesion complexes during homeostatic adaptation to hyperexcitation. Journal of neurochemistry 4 37654026
2024 Pharmacological inhibition of PLK2 kinase activity mitigates cognitive decline but aggravates APP pathology in a sex-dependent manner in APP/PS1 mouse model of Alzheimer's disease. Heliyon 3 39498012
2024 PLK2 inhibited oxidative stress and ameliorated hepatic ischemia-reperfusion injury through phosphorylating GSK3β. Journal of gastroenterology and hepatology 3 39563073
2025 A potential tumor suppressor role of PLK2 in glioblastoma. FEBS open bio 2 39927502
2025 PLK2 as a key regulator of glycolysis and immune dysregulation in polycystic ovary syndrome. Frontiers in immunology 2 41019094
2024 Rational design of potent phosphopeptide binders to endocrine Snk PBD domain by integrating machine learning optimization, molecular dynamics simulation, binding energetics rescoring, and in vitro affinity assay. European biophysics journal : EBJ 2 39611994
2023 Icariin Inhibits Overexpression and Aggregation of α-Synuclein in A53T α-Synuclein Transgenic Mice by Regulating Parkin and PLK2. Journal of integrative neuroscience 2 38176950
2022 Acute MPTP treatment decreases dendritic spine density of striatal medium spiny neurons via SNK-SPAR pathway in C57BL/6 mice. Synapse (New York, N.Y.) 2 36008099
2022 PLK2 Single Nucleotide Variant in Gastric Cancer Patients Affects miR-23b-5p Binding. Journal of gastric cancer 2 36316110
2001 Utilization of Drosophila eye to probe the functions of two mammalian serine/threonine kinases, Snk and HsHPK. Journal of biomedical science 2 11385299
2026 FAM117B Promotes Colorectal Cancer Progression by Enhancing DYRK1A-mediated Phosphorylation of PLK2. Cell biology international 1 41504297
2019 [MiR-30b Regulates the Cisplatin-Resistance of Human NK/T Cell Lypnphoma Cell Lines SNK-6 and YTS by Targeting the CCL22]. Zhongguo shi yan xue ye xue za zhi 1 31839047
2013 [Effect of doxorubicin on TRAIL resistance and TRAIL receptor expression in lymphoma cell line SNK-6 cells]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 1 24332050
2026 Abnormal PLK2 expression is associated with specific subtypes and may help risk stratification in acute myeloid leukemia. Discover oncology 0 41530586
2025 Decreased PLK2 promotes atrial fibrillation in diabetic mice through Nrf2/HO-1 pathway. Acta diabetologica 0 40080197
2025 KLF5 aggravates osteoarthritis progression by inhibiting chondrocyte autophagy via transcriptional activation of PLK2. Scientific reports 0 41198759
2025 BI-2536 attenuates IPF progression by inhibiting the PLK2/JNK/SP1 Signaling pathway in AT2 cells. International immunopharmacology 0 41237696

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