Affinage

NEK9

Serine/threonine-protein kinase Nek9 · UniProt Q8TD19

Length
979 aa
Mass
107.2 kDa
Annotated
2026-04-29
68 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NEK9 is a NIMA-family serine/threonine kinase that functions as a central signaling hub in mitotic spindle assembly, centrosome maturation, and primary ciliogenesis. During prophase, CDK1 and PLK1 sequentially phosphorylate and activate NEK9 at centrosomes, whereupon it initiates a kinase cascade by phosphorylating NEK6 (Ser206) and activating NEK7 through promotion of back-to-back dimerization that releases an autoinhibitory tyrosine; the NEK9→NEK6/7 cascade phosphorylates the kinesin Eg5 and TPX2 to drive centrosome separation and spindle formation, while NEK9 independently phosphorylates NEDD1/GCP-WD (Ser377) to recruit γ-tubulin for centrosome maturation (PMID:12840024, PMID:21642957, PMID:26522158, PMID:29276125, PMID:22818914). NEK9 oligomerization is modulated by DYNLL/LC8 binding, which is in turn regulated by autophosphorylation at Ser944, providing feedback control over NEK6 activation (PMID:21454704, PMID:23482567). Outside mitosis, NEK9 serves as a selective autophagy adaptor that targets MYH9/myosin IIA for LC3-dependent degradation, destabilizing the actin network to permit primary cilia formation; loss-of-function mutations in NEK9 cause lethal skeletal dysplasia with reduced ciliogenesis in humans (PMID:34078910, PMID:26908619).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2002 High

    Identification of NEK9/Nercc1 as a Ran-binding kinase that oligomerizes, autoactivates, and is required for mitotic spindle integrity established it as a new component of the mitotic machinery.

    Evidence Co-IP with Ran, in vitro autophosphorylation, anti-Nercc1 antibody microinjection causing spindle defects in mammalian cells

    PMID:12101123

    Open questions at the time
    • Ran-binding functional consequence unknown
    • upstream activating kinases not identified
    • mechanism of spindle defect not resolved
  2. 2003 High

    Demonstration that NEK9 directly phosphorylates NEK6 at Ser206 (and NEK7 similarly), producing ~20-fold activation, established the NEK9→NEK6/NEK7 kinase cascade as a mitotic signaling module.

    Evidence In vitro kinase assay with recombinant proteins, mass spectrometry phosphosite mapping, co-expression in cells

    PMID:12840024

    Open questions at the time
    • Downstream substrates of NEK6/7 in mitosis unknown
    • how NEK9 itself becomes activated in cells unclear
  3. 2005 High

    Localization of active NEK9 to centrosomes and its association with γ-TuRC, combined with immunodepletion/rescue in Xenopus extracts, placed NEK9 at centrosomes as a regulator of spindle assembly and microtubule organization.

    Evidence Immunofluorescence, Co-IP of γ-tubulin, Xenopus egg extract immunodepletion with rescue by recombinant XNercc

    PMID:16079175

    Open questions at the time
    • Direct phosphorylation target linking NEK9 to γ-TuRC recruitment not identified
    • contribution of Ran-dependent vs Ran-independent pathways unclear
  4. 2009 High

    The crystal structure of autoinhibited NEK7 revealed that Tyr97 blocks the active site, and that binding of the NEK9 C-terminal domain releases this inhibition, providing the first structural mechanism for NEK9-dependent activation of a downstream kinase.

    Evidence X-ray crystallography of NEK7, Y97F mutagenesis, in vitro kinase assay with NEK9-CTD

    PMID:19941817

    Open questions at the time
    • How NEK9-CTD physically engages NEK7 structurally unresolved
    • whether NEK6 is activated by the same mechanism unknown
  5. 2011 High

    Identification of the CDK1→PLK1→NEK9→NEK6/7→Eg5 phosphorylation cascade for prophase centrosome separation defined the complete upstream-to-downstream signaling chain driving this mitotic event.

    Evidence Sequential in vitro kinase assays, phosphomutant analysis, siRNA, live-cell imaging

    PMID:21642957

    Open questions at the time
    • Whether NEK9 has additional mitotic substrates besides Eg5 pathway
    • regulation by phosphatases not addressed
  6. 2011 High

    Discovery that DYNLL/LC8 binds NEK9, promotes its oligomerization and autoactivation, but competes with NEK6 binding — and that autophosphorylation at Ser944 reduces LC8 affinity — revealed a self-regulatory feedback loop controlling the kinase cascade.

    Evidence Co-IP, in vitro kinase assay, pull-down, mutational analysis

    PMID:21454704

    Open questions at the time
    • Temporal dynamics of LC8-NEK9 cycle in live cells unknown
    • stoichiometry of NEK9 oligomers not determined
  7. 2012 High

    NEK9 phosphorylation of NEDD1/GCP-WD at Ser377 was shown to recruit γ-tubulin to centrosomes independently of NEK6/7, establishing a second, parallel output of NEK9 in centrosome maturation.

    Evidence Xenopus egg extracts, in vitro kinase assay, phosphosite mutagenesis, mammalian cell siRNA and immunofluorescence

    PMID:22818914

    Open questions at the time
    • Other centrosome maturation substrates of NEK9 not surveyed
    • whether NEDD1 phosphorylation feeds back to spindle assembly unknown
  8. 2013 High

    Crystal structures of LC8 bound to the NEK9 Ser944 peptide (with and without phosphorylation) provided atomic-resolution explanation for how autophosphorylation disrupts the LC8 interaction, validating the feedback model.

    Evidence X-ray crystallography, ITC, fluorescence anisotropy

    PMID:23482567

    Open questions at the time
    • Full-length NEK9-LC8 complex structure unavailable
    • in vivo phosphorylation dynamics at Ser944 not measured
  9. 2015 High

    The crystal structure of NEK7(Y97F) bound to a NEK9 peptide (residues 810–828) showed the binding interface on the NEK7 C-lobe and revealed that NEK9 self-association promotes back-to-back NEK7 dimerization as the activation mechanism, completing the structural model.

    Evidence X-ray crystallography, in vitro kinase assay, biochemical mapping, mutagenesis

    PMID:26522158

    Open questions at the time
    • Whether NEK6 is activated through an identical dimerization mechanism not structurally confirmed
    • full NEK9-CTD:NEK7 complex structure still lacking
  10. 2016 Medium

    Human loss-of-function NEK9 mutations (homozygous p.Arg497*) were shown to cause lethal skeletal dysplasia with reduced proliferation and impaired ciliogenesis, establishing NEK9 as essential for human development and linking it to ciliopathy.

    Evidence Patient fibroblast analysis, Western blot, cell proliferation assay, flow cytometry, immunofluorescence for cilia

    PMID:26908619

    Open questions at the time
    • Molecular mechanism linking NEK9 loss to cilia defects not elucidated in this study
    • additional families/model organisms needed for genotype-phenotype confirmation
  11. 2017 High

    NEK9 phosphorylation of the TPX2 NLS, preventing importin binding and nuclear import, established a mechanism by which NEK9 retains TPX2 at centrosomes in prophase to organize microtubule asters and support centrosome separation.

    Evidence In vitro kinase assay, phosphomutant analysis, siRNA, live-cell imaging

    PMID:29276125

    Open questions at the time
    • Other NEK9 substrates regulated by importin-dependent nuclear-cytoplasmic shuttling not explored
    • whether phosphorylation is reversed by specific phosphatases unknown
  12. 2021 High

    Discovery that NEK9 acts as a selective autophagy adaptor for MYH9/myosin IIA via its LIR motif, promoting actin network destabilization to enable primary ciliogenesis, defined a kinase-independent function of NEK9 outside mitosis and explained the ciliopathy phenotype of NEK9-mutant patients.

    Evidence Co-IP, autophagy assays, LIR-mutant knockin mice with reduced kidney cilia, MYH9 depletion rescue

    PMID:34078910

    Open questions at the time
    • Whether NEK9 kinase activity also contributes to ciliogenesis alongside autophagy adaptor function
    • additional autophagy cargo of NEK9 not surveyed
  13. 2024 Medium

    Identification of USP19-mediated deubiquitylation at K525 stabilizing NEK9, which then phosphorylates Raptor at Ser792 to inhibit mTORC1 and induce autophagic cell death, linked NEK9 to mTOR regulation and provided a new mechanism for its tumor-suppressive role.

    Evidence In vitro ubiquitination/deubiquitination assay, in vitro kinase assay, Co-IP, Atg5 knockdown rescue

    PMID:39627360

    Open questions at the time
    • Whether Raptor phosphorylation by NEK9 occurs in non-cancer contexts unknown
    • independent validation in additional cell types needed
    • relationship to NEK9 mitotic functions unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The full repertoire of NEK9 substrates beyond those characterized (NEK6, NEK7, NEDD1, Eg5/via cascade, TPX2, ARHGEF2, TRIM28, CTTN, Raptor) remains undefined, and how NEK9's mitotic kinase cascade, autophagy adaptor, and potential mTOR-regulatory functions are coordinated across the cell cycle is unresolved.
  • Systematic phosphoproteomics of NEK9 substrates in mitosis lacking
  • structural basis for NEK9 autophagy adaptor function (LIR-LC3 interface) not solved
  • cell-cycle-dependent partitioning of NEK9 between kinase and adaptor roles unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 7 GO:0140096 catalytic activity, acting on a protein 7 GO:0060090 molecular adaptor activity 1
Localization
GO:0005815 microtubule organizing center 3 GO:0005634 nucleus 2 GO:0005856 cytoskeleton 1
Pathway
R-HSA-1640170 Cell Cycle 7 R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-162582 Signal Transduction 2 R-HSA-9612973 Autophagy 2
Partners
DYNLL1MYH9NEDD1NEK6NEK7PLK1RANTPX2
Complex memberships
γ-TuRC (associated)

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 NEK9/Nercc1 binds to the Ran GTPase through both its catalytic and RCC1-like domains, preferring RanGDP in vivo; it also binds NEK6 and exists as a homooligomer that can autoactivate in vitro by autophosphorylation. Microinjection of anti-Nercc1 antibodies in prophase causes spindle abnormalities and chromosomal misalignment, establishing a role in mitotic progression. Co-immunoprecipitation, in vitro kinase assay (autophosphorylation), microinjection, cell imaging Genes & development High 12101123
2003 NEK9/Nercc1 directly phosphorylates and activates NEK6 at Ser206 on its activation loop in vitro (~20–25-fold activation), and activates NEK7 similarly; coexpression of activated Nercc1 stimulates NEK6 activity in cells, establishing a NEK9→NEK6/NEK7 mitotic kinase cascade. In vitro kinase assay with recombinant proteins, co-expression in cells, mass spectrometry identification of phosphorylation site The Journal of biological chemistry High 12840024
2003 NEK9 forms a stable ~600 kDa complex with the FACT (Spt16-Pob3) chromatin remodeling complex in interphase nuclei; active NEK9 in this complex is marked by phosphorylation at Thr210 in the activation loop, and RNAi depletion of NEK9 delays G1 and S phase progression. Co-immunoprecipitation, cell cycle analysis (flow cytometry), dsRNAi knockdown The Journal of biological chemistry Medium 14660563
2005 Active NEK9/Nercc1 (phosphorylated at Thr210) localizes to centrosomes and spindle poles in early mitosis; in Xenopus egg extracts, NEK9 co-precipitates γ-tubulin and components of the γ-TuRC. Immunodepletion of XNercc1 from egg extracts delays spindle assembly and produces fewer bipolar spindles and abnormal Ran-asters, phenotypes rescued by recombinant XNercc. Immunoprecipitation, immunofluorescence, Xenopus egg extract reconstitution, immunodepletion rescue assay Molecular biology of the cell High 16079175
2007 Adenovirus E1A interacts with NEK9 and diminishes the amount of NEK9 in the nucleus, redirecting its subcellular distribution; the interaction depends on the N-terminal sequences of E1A and the RCC1-like domain of NEK9. Co-immunoprecipitation, subcellular fractionation, immunofluorescence, deletion mutant analysis Journal of cellular physiology Medium 17443675
2009 Crystal structure of NEK7 revealed an autoinhibited conformation where Tyr97 protrudes into the active site, blocking the αC helix; binding of the NEK9 non-catalytic C-terminal domain (CTD) to NEK7 releases this autoinhibitory tyrosine, activating NEK7. Tyr97Phe mutation renders NEK7 constitutively active, and this is not further increased by NEK9-CTD, confirming the mechanism. X-ray crystallography, site-directed mutagenesis, in vitro kinase assay Molecular cell High 19941817
2011 NEK9 is activated during prophase at centrosomes through a two-step mechanism: first phosphorylated by CDK1, then directly phosphorylated and activated by PLK1. Activated NEK9 then activates NEK6/7, which phosphorylate the mitotic kinesin Eg5 at Ser1033; together with the CDK1 site Thr926, this promotes Eg5 accumulation at centrosomes and is required for prophase centrosome separation. In vitro kinase assay, co-immunoprecipitation, phosphomutant analysis, live-cell imaging, siRNA knockdown The EMBO journal High 21642957
2011 NEK9 binds DYNLL/LC8 through a (K/R)XTQT motif adjacent to its C-terminal coiled-coil; LC8 binding promotes NEK9 multimerization and accelerates NEK9 autoactivation, but interferes with NEK9 binding to and activation of NEK6. NEK9 autophosphorylation at Ser944, immediately N-terminal to the LC8-binding motif, reduces LC8 affinity, providing a feedback regulatory mechanism. Co-immunoprecipitation, in vitro kinase assay, mutant analysis, pull-down The Journal of biological chemistry High 21454704
2012 NEK9 phosphorylates NEDD1/GCP-WD on Ser377, driving NEDD1 recruitment to centrosomes and thereby enabling γ-tubulin recruitment during centrosome maturation in mitotic cells. This function requires PLK1-dependent activation of NEK9 but is independent of NEK6/NEK7. Xenopus egg extracts, in vitro kinase assay, phosphosite mutagenesis, immunofluorescence in mammalian cells, siRNA knockdown Current biology : CB High 22818914
2013 Crystal structures of LC8 bound to a Nek9 peptide with and without phosphorylation at Ser944 show how phosphorylation at this site sterically reduces LC8 binding affinity by altering the peptide conformation at the binding interface. X-ray crystallography, biophysical binding assays (ITC, fluorescence anisotropy) The Journal of biological chemistry High 23482567
2013 NEK9 depletion by siRNA in cancer cells causes failure of cytokinesis, override of mitotic checkpoint under incorrect chromosome alignment (micronucleated phenotype), and compromised nocodazole-induced mitotic arrest, demonstrating a role in spindle dynamics and the mitotic checkpoint. siRNA knockdown, live-cell imaging, flow cytometry Biochemical and biophysical research communications Medium 23665325
2013 NEK9 depletion leads to spontaneous DNA damage accumulation, impairs recovery from replication arrest, and reduces CHK1 autophosphorylation and kinase activity; NEK9 physically complexes with CHK1, placing NEK9 upstream in the replication stress response. siRNA knockdown, Co-immunoprecipitation, immunofluorescence (RPA70 foci, γH2AX), kinase assay Nucleic acids research Medium 25217585
2015 Crystal structure of NEK7(Y97F) bound to a NEK9 peptide (residues 810–828) reveals the binding site on the C-lobe of NEK7; NEK7(Y97F) crystallizes as a back-to-back N-lobe dimer coupled to the conformation of residue 97. Self-association of the NEK9 CTD is required for NEK7 activation, indicating NEK9 activates NEK7 by promoting back-to-back dimerization that releases the autoinhibitory tyrosine. X-ray crystallography, in vitro kinase assay, mutational analysis, biochemical mapping Nature communications High 26522158
2015 NEK9 functions as a transcriptional repressor that, together with adenovirus E1A, silences p53-inducible GADD45A gene expression; NEK9 localizes to viral replication centers and associates with viral and cellular promoters. NEK9 depletion reduces viral genome replication, while overexpression enhances it. ChIP (chromatin immunoprecipitation), promoter luciferase reporter assay, siRNA knockdown, immunofluorescence co-localization Journal of virology Medium 26676776
2016 Somatic gain-of-function missense mutations in NEK9 (kinase or RCC1 domains) cause nevus comedonicus by increasing phosphorylation at Thr210 (activation loop), disrupting normal follicular differentiation with expansion of keratin-15-positive bulge cells and ectopic keratin-10 expression. Whole-exome sequencing, in vitro kinase activity assay (pThr210 as readout), immunohistochemistry American journal of human genetics Medium 27153399
2016 NEK9 loss-of-function (homozygous stop-gain p.Arg497*) in humans causes lethal skeletal dysplasia with significant reduction in cell proliferation and a delay in cell cycle progression in patient fibroblasts; patient fibroblasts also show reduced primary cilia number and length. Patient fibroblast analysis, Western blot (protein loss), cell proliferation assay, flow cytometry (cell cycle), immunofluorescence (cilia) Human molecular genetics Medium 26908619
2017 NEK9 phosphorylates the nuclear localization signal (NLS) of TPX2, preventing its interaction with importin and nuclear import; a centrosomal pool of TPX2 (dependent on RHAMM/HMMR and NEK9) in prophase is required for microtubule aster organization, Eg5 localization, and prophase centrosome separation. In vitro kinase assay, phosphomutant/phosphomimetic analysis, siRNA knockdown, immunofluorescence, live-cell imaging Current biology : CB High 29276125
2020 EML4-ALK variant 3 recruits NEK9 and NEK7 to microtubules via the EML4 microtubule-binding region; constitutively active NEK9 perturbs cell morphology and accelerates cell migration in a microtubule- and NEK7-dependent manner, establishing NEK9→NEK7 as a downstream pathway of EML4-ALK V3 promoting microtubule stabilization and migration. Co-immunoprecipitation, constitutively active kinase expression, siRNA knockdown, cell migration assays, immunofluorescence Journal of cell science Medium 32184261
2021 NEK9 acts as an autophagy adaptor for MYH9 (myosin IIA) through a LC3-interacting region (LIR); NEK9 interacts with MYH9 and promotes its selective autophagic degradation. Loss of the LIR in NEK9 causes MYH9 accumulation, stabilization of the actin network, and impaired primary cilia formation both in vitro and in vivo (mice with NEK9 LIR mutation show reduced kidney cilia). Co-immunoprecipitation, autophagy assays, LIR mutant knockin mice, immunofluorescence (cilia), MYH9 depletion rescue Nature communications High 34078910
2021 NEK9 directly interacts with PRLR-SF (short isoform of prolactin receptor) and acts as an intermediator linking PRLR-SF to Hippo pathway activation; NEK9-Hippo signaling suppresses the pentose phosphate pathway by reducing G6PD and TKT expression via TEAD1. Co-immunoprecipitation, proximity ligation assay, in vitro kinase assay, luciferase reporter, ChIP Theranostics Medium 33664869
2021 NEK9 directly phosphorylates ARHGEF2 (a RhoGEF); this phosphorylation is the key step regulating RhoA activation and cell motility in gastric cancer cells. IL-6/STAT3 signaling transcriptionally suppresses miR-520f-3p, relieving its inhibition on NEK9. In vitro kinase assay, phosphoproteomics, Co-immunoprecipitation, GST pull-down, luciferase/ChIP Theranostics Medium 33500736
2023 NEK9 interacts with ROBO1 (the receptor for CAF-derived SLIT2) via its kinase domain; SLIT2 enhances this interaction. NEK9 directly phosphorylates TRIM28 and cortactin (CTTN), promoting cytoskeletal reorganization and gastric cancer cell metastasis. Mass spectrometry interactome, domain analysis, Co-immunoprecipitation, in vitro kinase assay Cell death & disease Medium 37443302
2024 USP19 deubiquitylates NEK9 at K525 (removing K48-linked polyubiquitin) to stabilize it; NEK9 in turn phosphorylates Raptor (the regulatory subunit of mTORC1) at Ser792, inhibiting mTORC1 signaling and inducing autophagic cell death in pancreatic cancer cells. Co-immunoprecipitation, in vitro ubiquitination/deubiquitination assay, in vitro kinase assay, Atg5 knockdown and lysosome inhibitor rescue Cell death and differentiation Medium 39627360
2012 NEK9 localizes to spindle poles at metaphase stages and to the midbody at anaphase/telophase in mouse oocytes and early embryos. Depletion by morpholino injection causes severely defective spindles, misaligned chromosomes, MI arrest, loss of γ-tubulin from spindle poles, and retention of SAC protein Bub3 at kinetochores. Morpholino knockdown, confocal immunofluorescence, live-cell imaging in mouse oocytes Cell cycle Medium 23159858

Source papers

Stage 0 corpus · 68 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3. Nature genetics 170 23793029
2008 NEK8 mutations affect ciliary and centrosomal localization and may cause nephronophthisis. Journal of the American Society of Nephrology : JASN 168 18199800
2003 A mitotic cascade of NIMA family kinases. Nercc1/Nek9 activates the Nek6 and Nek7 kinases. The Journal of biological chemistry 154 12840024
2011 Nek9 is a Plk1-activated kinase that controls early centrosome separation through Nek6/7 and Eg5. The EMBO journal 147 21642957
2002 Nercc1, a mammalian NIMA-family kinase, binds the Ran GTPase and regulates mitotic progression. Genes & development 122 12101123
2013 NEK8 links the ATR-regulated replication stress response and S phase CDK activity to renal ciliopathies. Molecular cell 117 23973373
2008 Nek8 regulates the expression and localization of polycystin-1 and polycystin-2. Journal of the American Society of Nephrology : JASN 95 18235101
2004 Nek8, a NIMA family kinase member, is overexpressed in primary human breast tumors. Gene 86 15019993
2013 Mutations in NEK8 link multiple organ dysplasia with altered Hippo signalling and increased c-MYC expression. Human molecular genetics 82 23418306
2010 Inv acts as a molecular anchor for Nphp3 and Nek8 in the proximal segment of primary cilia. Cytoskeleton (Hoboken, N.J.) 81 20169535
2009 An autoinhibitory tyrosine motif in the cell-cycle-regulated Nek7 kinase is released through binding of Nek9. Molecular cell 81 19941817
2016 Novel NEK8 Mutations Cause Severe Syndromic Renal Cystic Dysplasia through YAP Dysregulation. PLoS genetics 76 26967905
2012 Nek9 phosphorylation of NEDD1/GCP-WD contributes to Plk1 control of γ-tubulin recruitment to the mitotic centrosome. Current biology : CB 68 22818914
2005 Active Nercc1 protein kinase concentrates at centrosomes early in mitosis and is necessary for proper spindle assembly. Molecular biology of the cell 61 16079175
2011 The Nek8 protein kinase, mutated in the human cystic kidney disease nephronophthisis, is both activated and degraded during ciliogenesis. Human molecular genetics 60 22106379
2012 A novel mutation causing nephronophthisis in the Lewis polycystic kidney rat localises to a conserved RCC1 domain in Nek8. BMC genomics 57 22899815
2017 Nek9 Phosphorylation Defines a New Role for TPX2 in Eg5-Dependent Centrosome Separation before Nuclear Envelope Breakdown. Current biology : CB 52 29276125
2013 Loss of the ciliary kinase Nek8 causes left-right asymmetry defects. Journal of the American Society of Nephrology : JASN 52 23274954
2002 Purification, cloning, and characterization of Nek8, a novel NIMA-related kinase, and its candidate substrate Bicd2. The Journal of biological chemistry 51 11864968
2015 Mechanistic basis of Nek7 activation through Nek9 binding and induced dimerization. Nature communications 50 26522158
2018 Proteomic analysis discovers the differential expression of novel proteins and phosphoproteins in meningioma including NEK9, HK2 and SET and deregulation of RNA metabolism. EBioMedicine 48 30594554
2015 ANKS6 is the critical activator of NEK8 kinase in embryonic situs determination and organ patterning. Nature communications 47 25599650
2021 NEK9 regulates primary cilia formation by acting as a selective autophagy adaptor for MYH9/myosin IIA. Nature communications 46 34078910
2003 Nek9, a novel FACT-associated protein, modulates interphase progression. The Journal of biological chemistry 44 14660563
2005 Nek8 mutation causes overexpression of galectin-1, sorcin, and vimentin and accumulation of the major urinary protein in renal cysts of jck mice. Molecular & cellular proteomics : MCP 43 15872312
2021 The short isoform of PRLR suppresses the pentose phosphate pathway and nucleotide synthesis through the NEK9-Hippo axis in pancreatic cancer. Theranostics 41 33664869
2007 Pkd1 and Nek8 mutations affect cell-cell adhesion and cilia in cysts formed in kidney organ cultures. American journal of physiology. Renal physiology 41 17928412
2023 Cancer associated fibroblast derived SLIT2 drives gastric cancer cell metastasis by activating NEK9. Cell death & disease 40 37443302
2016 Recessive NEK9 mutation causes a lethal skeletal dysplasia with evidence of cell cycle and ciliary defects. Human molecular genetics 40 26908619
2016 Somatic Mutations in NEK9 Cause Nevus Comedonicus. American journal of human genetics 40 27153399
2017 Dabrafenib inhibits the growth of BRAF-WT cancers through CDK16 and NEK9 inhibition. Molecular oncology 39 29112787
2020 EML4-ALK V3 oncogenic fusion proteins promote microtubule stabilization and accelerated migration through NEK9 and NEK7. Journal of cell science 38 32184261
2021 NEK9, a novel effector of IL-6/STAT3, regulates metastasis of gastric cancer by targeting ARHGEF2 phosphorylation. Theranostics 37 33500736
2014 A gemcitabine sensitivity screen identifies a role for NEK9 in the replication stress response. Nucleic acids research 37 25217585
2023 Certain heterozygous variants in the kinase domain of the serine/threonine kinase NEK8 can cause an autosomal dominant form of polycystic kidney disease. Kidney international 34 37598857
2008 Defects in ciliary localization of Nek8 is associated with cystogenesis. Pediatric nephrology (Berlin, Germany) 30 18189147
2013 NEK9 depletion induces catastrophic mitosis by impairment of mitotic checkpoint control and spindle dynamics. Biochemical and biophysical research communications 27 23665325
2012 Nek9 regulates spindle organization and cell cycle progression during mouse oocyte meiosis and its location in early embryo mitosis. Cell cycle (Georgetown, Tex.) 26 23159858
2013 Structural analysis of the regulation of the DYNLL/LC8 binding to Nek9 by phosphorylation. The Journal of biological chemistry 24 23482567
2016 NEK8 regulates DNA damage-induced RAD51 foci formation and replication fork protection. Cell cycle (Georgetown, Tex.) 23 27892797
2011 DYNLL/LC8 protein controls signal transduction through the Nek9/Nek6 signaling module by regulating Nek6 binding to Nek9. The Journal of biological chemistry 23 21454704
2013 Nek8 couples renal ciliopathies to DNA damage and checkpoint control. Molecular cell 22 23973371
2007 Adenovirus E1A proteins direct subcellular redistribution of Nek9, a NimA-related kinase. Journal of cellular physiology 21 17443675
2015 The Dual Nature of Nek9 in Adenovirus Replication. Journal of virology 19 26676776
2012 The ciliary protein Nek8/Nphp9 acts downstream of Inv/Nphp2 during pronephros morphogenesis and left-right establishment in zebrafish. FEBS letters 19 22687244
2015 Compound heterozygous mutations in NEK8 in siblings with end-stage renal disease with hepatic and cardiac anomalies. American journal of medical genetics. Part A 18 26697755
2014 NEK9-dependent proliferation of cancer cells lacking functional p53. Scientific reports 17 25131192
2023 Overexpression of the NEK9-EG5 axis is a novel metastatic marker in pathologic stage T3 colon cancer. Scientific reports 12 36611072
2023 NEK8 regulates colorectal cancer progression via phosphorylating MYC. Cell communication and signaling : CCS 12 37596667
2024 Involvement of NEK2 and NEK9 in LPS - induced endothelial barrier dysfunction. Microvascular research 9 38176677
2024 USP19 potentiates autophagic cell death via inhibiting mTOR pathway through deubiquitinating NEK9 in pancreatic cancer. Cell death and differentiation 8 39627360
2025 NEK8 promotes the progression of gastric cancer by reprogramming asparagine metabolism. Molecular medicine (Cambridge, Mass.) 7 39762761
2022 NEK8-Associated Nephropathies: Do Autosomal Dominant Forms Exist? Nephron 6 36215968
2025 NEK8, a NIMA-family protein kinase at the core of the ciliary INV complex. Cell communication and signaling : CCS 4 40189576
2022 Study on the Expression of lncRNA ATB and Nek9 in Breast Cancer Patients Based on Q-PCR Technology and Its Relationship with the Disease. Contrast media & molecular imaging 4 35935324
2022 Never-in-Mitosis A-Related Kinase 8 (NEK8) Regulates Adipogenesis, Glucose Homeostasis, and Obesity. Oxidative medicine and cellular longevity 4 36506932
2025 FAM49B drives colorectal cancer progression by stabilizing c-Myc through NEK9 phosphorylation. BioFactors (Oxford, England) 2 39780509
2023 Novel variants of NEK9 associated with neonatal arthrogryposis: Two case reports and a literature review. Frontiers in genetics 2 36712877
2025 NEK9-mediated Wnt signalling repressor TLE3 rewires Docetaxel resistance in cancer cells by inducing pyroptosis. British journal of cancer 1 40926063
2021 Synthesis and structure-activity relationships of targeted protein degraders for the understudied kinase NEK9. Current research in chemical biology 1 40837099
2026 Multi-omics profiling of sodium-overload (NECSO) programs identifies NEK8 as a central driver of colorectal cancer progression through single-cell and spatial transcriptomics. Frontiers in immunology 0 41743703
2026 NEK8 kinase-mediated lactate increase impairs antitumor immunity decreasing radiotherapy sensitivity in colorectal cancer. Nature communications 0 41904143
2025 Overexpression of the NEK8 kinase inhibits homologous recombination. bioRxiv : the preprint server for biology 0 39975112
2025 Visualizing NEK9 in action: aptamer-based fluorescent probes for real-time live-cell imaging. Nucleosides, nucleotides & nucleic acids 0 40927996
2025 Overexpression of the NEK8 kinase inhibits homologous recombination. DNA repair 0 41101173
2025 NEK8 stabilization via USP51-mediated deubiquitination promotes colorectal cancer progression. Pathology, research and practice 0 41475333
2021 Giant nevus comedonicus of the entire lower left limb protecting from the associated bullous pemphigoid: A hypothetical role of NEK9 mutation? The Journal of dermatology 0 34002421
2020 Nek9,a sensitive immunohistochemical marker for Schwannian, melanocytic and myogenic tumours. Journal of clinical pathology 0 32792414