Affinage

VRK2

Serine/threonine-protein kinase VRK2 · UniProt Q86Y07

Length
508 aa
Mass
58.1 kDa
Annotated
2026-04-28
41 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

VRK2 is a serine/threonine kinase that functions as a signaling scaffold and phosphorylation-dependent regulator of MAPK, NF-κB, autophagy, innate immune, and stress granule pathways, with isoform-specific subcellular compartmentalization directing its diverse outputs. The membrane-anchored VRK2A isoform sequesters JIP1–TAK1–MKK7 and KSR1–MEK1 complexes at the endoplasmic reticulum to attenuate JNK and ERK signaling, promotes VDAC1 oligomerization and mtDNA release to activate cGAS-mediated antiviral responses, and facilitates lysosomal Akt accumulation to drive autophagy, whereas the nuclear/cytoplasmic VRK2B isoform stabilizes p53 by reducing Mdm2-mediated ubiquitination (PMID:16704422, PMID:18286207, PMID:20679487, PMID:29872222, PMID:33785841). VRK2 directly phosphorylates substrates including p53-Thr18, NFAT1-Ser32, IKKβ-Ser177/181, MYC-Ser281/293, TKT-Thr287, GAPDH-Ser151, and G3BP1, thereby controlling transcription factor activity, protein stability, NF-κB activation, immune evasion, and stress granule dynamics (PMID:23105117, PMID:35173553, PMID:41073389, PMID:37653031, PMID:40204710). VRK2 acts as a synthetic lethal paralog of VRK1: epigenetic silencing of VRK2 in glioblastoma renders cells dependent on VRK1 for BAF phosphorylation and nuclear envelope integrity during mitosis (PMID:36069976, PMID:36040810).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1997 Medium

    Identification of VRK2 as a novel kinase paralogous to vaccinia B1R established the VRK family and predicted serine/threonine kinase activity, raising the question of what VRK2 phosphorylates and where it acts.

    Evidence cDNA cloning and sequence analysis of human VRK2

    PMID:9344656

    Open questions at the time
    • No demonstrated kinase activity
    • No known substrates
    • No subcellular localization data
  2. 2006 High

    Discovery of two VRK2 splice isoforms with distinct localizations (ER/mitochondrial-anchored VRK2A vs. nuclear/cytoplasmic VRK2B) and demonstration that both phosphorylate p53 at Thr18 resolved the question of VRK2 enzymatic activity and revealed isoform-specific functional outputs—VRK2B stabilizes p53 while VRK2A does not.

    Evidence Subcellular fractionation, confocal microscopy, in vitro kinase assay, co-IP in human cell lines

    PMID:16704422

    Open questions at the time
    • Whether VRK2A membrane anchoring has signaling platform functions
    • In vivo relevance of p53-Thr18 phosphorylation by VRK2
  3. 2008 High

    Demonstration that VRK2A sequesters the JIP1–TAK1–MKK7 signalosome and prevents JNK activation established VRK2 as a scaffold-dependent negative regulator of MAP kinase cascades, beyond its kinase activity alone.

    Evidence Reciprocal co-IPs of JIP1 complex components, shRNA/siRNA knockdown, IL-1β-stimulated reporter assays

    PMID:18286207

    Open questions at the time
    • Whether kinase activity is required for scaffold function
    • Structural basis of VRK2–JIP1 interaction
  4. 2008 High

    Identification of Ran-GTPase as a nucleotide-state-dependent inhibitor of VRK2 kinase activity revealed an upstream regulatory mechanism, with RanGDP inhibiting and RanGTP relieving repression.

    Evidence Mass spectrometry, GST pulldown, reciprocal IP, in vitro kinase assay with Ran nucleotide-state mutants

    PMID:18617507

    Open questions at the time
    • Physiological context in which Ran regulates VRK2
    • Whether nuclear import/export cycle controls VRK2B activity in vivo
  5. 2010 High

    VRK2A was shown to directly bind MEK1 and KSR1 and block ERK phosphorylation downstream of EGF, extending the scaffold-sequestration model from JNK to ERK/MAPK signaling and linking VRK2 expression inversely to ErbB2 in breast cancer.

    Evidence Co-IP, phospho-ERK/MEK Western blots, siRNA knockdown, reporter assays, immunohistochemistry in breast carcinoma

    PMID:20679487

    Open questions at the time
    • Whether VRK2 kinase activity modifies KSR1 or MEK directly
    • Causal role in breast cancer progression
  6. 2012 High

    Biochemical isolation of a 600–1000 kDa VRK2A–KSR1–MEK1 complex at the ER confirmed that VRK2A physically anchors MAPK scaffolds to endomembranes, providing a structural explanation for how VRK2A sequesters signaling components away from cytosolic ERK.

    Evidence Size-exclusion chromatography, subcellular fractionation, direct binding assays, siRNA disassembly of complex

    PMID:22752157

    Open questions at the time
    • Stoichiometry and cryo-EM/structural model of the complex
    • Dynamic regulation upon growth factor stimulation
  7. 2012 High

    Identification of NFAT1-Ser32 as a direct VRK2 phosphorylation site that enhances NFAT1-dependent COX-2 transcription and tumor invasion expanded VRK2's substrate repertoire to transcription factors controlling inflammation and metastasis.

    Evidence In vitro kinase assay, co-IP, transcriptional reporter, siRNA knockdown, invasion assay

    PMID:23105117

    Open questions at the time
    • In vivo validation of NFAT1-Ser32 phosphorylation
    • Whether calcineurin-NFAT pathway cross-regulates VRK2
  8. 2018 High

    VRK2A was found to interact with Akt1/2 at lysosomes and promote lysosomal pAkt accumulation required for TFEB nuclear translocation and autophagy, connecting VRK2 to a new organelle (lysosome) and a new pathway (autophagy).

    Evidence TOF/MS, reciprocal co-IP, BiFC, immunofluorescence, siRNA knockdown in human cells

    PMID:29872222

    Open questions at the time
    • Whether VRK2 directly phosphorylates Akt or acts as a scaffold
    • Mechanism of VRK2A trafficking from ER to lysosomes
  9. 2021 High

    VRK2 was shown to promote VDAC1 oligomerization and mtDNA release, activating cGAS-mediated innate immunity; VRK2-knockout mice displayed impaired antiviral responses and increased mortality, establishing an in vivo immune function.

    Evidence VRK2 KO mice, VDAC1 oligomerization assay, co-IP of VRK2–VDAC1, viral infection models, cGAS signaling readouts

    PMID:33785841

    Open questions at the time
    • Whether VRK2 directly phosphorylates VDAC1
    • Mechanism linking VRK2 to VDAC1 oligomerization
  10. 2022 High

    Two independent studies demonstrated VRK1–VRK2 synthetic lethality: VRK2 promoter methylation silences VRK2 in most glioblastomas, and VRK1 loss in this context abolishes BAF phosphorylation, causing nuclear envelope defects, mitotic arrest, and cell death—establishing VRK2 as a redundant BAF kinase and a therapeutic vulnerability context.

    Evidence CRISPR screens, ectopic VRK2 rescue, BAF phosphorylation assays, patient-derived xenografts

    PMID:36040810 PMID:36069976

    Open questions at the time
    • Whether VRK2 directly phosphorylates BAF or acts through an intermediate
    • Clinical translation of VRK1 inhibition in VRK2-methylated tumors
  11. 2022 Medium

    Direct phosphorylation of IKKβ at Ser177/181 by VRK2 connected VRK2 kinase activity to canonical NF-κB pathway activation and pancreatic cancer growth, expanding the repertoire of VRK2-activated inflammatory pathways.

    Evidence In vitro kinase assay, co-IP, IKKβ inhibitor rescue, tumor organoid and xenograft models

    PMID:35173553

    Open questions at the time
    • Single-lab finding; independent replication needed
    • Relative contribution of VRK2 vs. TAK1 to IKKβ activation in vivo
  12. 2023 Medium

    Phosphorylation of TKT-Thr287 and GAPDH-Ser151 by VRK2 was shown to drive metabolic enzyme activation, NF-κB signaling, and PD-L1 upregulation through feed-forward loops, linking VRK2 kinase activity to immune evasion in hepatocellular carcinoma.

    Evidence In vitro kinase assays, ubiquitination assays, co-IP, transgenic mouse models, patient tissue IHC

    PMID:37450367 PMID:37653031

    Open questions at the time
    • Both studies from single lab; independent replication needed
    • Structural basis for VRK2 substrate selectivity across diverse targets
  13. 2025 High

    VRK2 was shown to stabilize MYC by phosphorylating Ser281/293, competing with SCF-FBXO24-mediated ubiquitination, establishing a MYC–VRK2–PD-L1 self-reinforcing transcriptional circuit in HCC, and VRK2 phosphorylation of G3BP1 was identified as an inhibitor of stress granule assembly.

    Evidence In vitro kinase assays, ubiquitination competition assays, proteasomal degradation assays, tumor models; stress granule imaging with VRK2 OE/KD

    PMID:40204710 PMID:41073389

    Open questions at the time
    • Specific G3BP1 phosphorylation site not mapped
    • Whether MYC stabilization operates outside HCC
  14. 2026 Medium

    Microglia-specific VRK2 expression in the thalamus was shown to regulate tonic GABAergic currents in neurons through non-cell-autonomous TNFα-dependent signaling that controls astrocytic GABA synthesis, providing the first neuronal circuit-level function for VRK2.

    Evidence VRK2-deficient mice, single-cell transcriptomics, electrophysiology, pharmacological TNFα inhibition and microglial depletion

    PMID:41263186

    Open questions at the time
    • Single-lab finding; not yet replicated
    • Direct VRK2 substrates in microglia not identified
    • Relevance to schizophrenia GWAS associations not mechanistically linked

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis for VRK2's broad substrate specificity, whether VRK2 directly phosphorylates BAF and VDAC1, the in vivo relevance of Ran-dependent regulation, and the mechanism linking VRK2 to psychiatric disease risk identified by GWAS.
  • No crystal structure of VRK2 kinase domain
  • Direct BAF phosphorylation by VRK2 not demonstrated in vitro
  • No mechanistic link between VRK2 and schizophrenia risk variants

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005739 mitochondrion 3 GO:0005783 endoplasmic reticulum 2 GO:0005634 nucleus 1 GO:0005764 lysosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1640170 Cell Cycle 2 R-HSA-168256 Immune System 2 R-HSA-9612973 Autophagy 1
Partners
AKT1G3BP1JIP1KSR1MEK1MYCRACK1VDAC1
Complex memberships
JIP1–TAK1–MKK7–VRK2 complexVRK2A–KSR1–MEK1 ER complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 VRK2 was identified as a novel putative serine/threonine kinase with 38.7% identity to vaccinia virus B1R kinase over 300 amino acids, predicting a protein of 508 amino acids with structural similarity to VRK1. cDNA cloning, sequence analysis, Northern blot Genomics Medium 9344656
2006 VRK2 exists as two isoforms (VRK2A, 508 aa; VRK2B, 397 aa) due to alternative splicing. VRK2A contains a C-terminal hydrophobic region that anchors it to endoplasmic reticulum and mitochondrial membranes (colocalizing with calreticulin, calnexin, and mitotracker), whereas VRK2B localizes to cytoplasm and nucleus. Both isoforms phosphorylate p53 at Thr18 in vitro, but only nuclear VRK2B induces p53 stabilization by reducing Mdm2-mediated ubiquitination and increasing p300-mediated acetylation. Subcellular fractionation, confocal microscopy, in vitro kinase assay, co-immunoprecipitation, overexpression and knockdown The FEBS journal High 16704422
2006 VRK2 interacts specifically with EBV BHRF1 (a Bcl-2 homolog) through its C-terminal 108 aa region; BHRF1 BH4 and BH1 domains (aa 1-18 and 89-142) are critical for this interaction. VRK2 overexpression modestly enhances cell survival, and this enhancement is augmented in the presence of BHRF1. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, confocal microscopy, deletion mutant analysis, cell survival assay The Journal of general virology Medium 16963744
2008 VRK2 stably interacts with the JIP1 scaffold protein as well as TAK1 and MKK7, but not JNK, forming oligomeric complexes. VRK2 binding to the JIP1 signalosome prevents JNK association, reduces JNK phosphorylation, and downregulates AP1-dependent transcription in response to IL-1β. Knockdown of VRK2 increases the IL-1β transcriptional response. Co-immunoprecipitation, shRNA knockdown, siRNA, transcriptional reporter assay PloS one High 18286207
2008 Ran GTPase interacts with VRK2 (and VRK1/VRK3) and inhibits VRK2 kinase activity. The interaction is stronger with inactive RanT24N (GDP-locked). RanGDP inhibits VRK2 autophosphorylation and substrate phosphorylation, while constitutively active RanGTP (or RanL43E) relieves this inhibition. Mass spectrometry, GST pulldown of endogenous proteins, reciprocal immunoprecipitation, in vitro kinase assay, autophosphorylation assay Molecular & cellular proteomics High 18617507
2008 p53-induced downregulation of VRK2 protein is prevented by p300/CBP through their C/H3 domain binding directly to the p53 transactivation domain, but not by PCAF, indicating cofactor-specific modulation of VRK2 levels. Western blot, co-immunoprecipitation, domain mapping with deletion mutants, overexpression assays PloS one Medium 18612383
2010 VRK2A inhibits the MAPK/ERK signaling pathway through a direct protein-protein interaction with MEK and KSR1, acting between MEK and ERK (MEK remains phosphorylated while ERK phosphorylation is blocked). VRK2 knockdown increases ERK phosphorylation and EGF-dependent SRE transcription. VRK2 and ErbB2 protein levels are inversely correlated in human breast carcinoma. Co-immunoprecipitation, Western blot (phospho-ERK/MEK), siRNA knockdown, transcriptional reporter assay, immunohistochemistry in tumor samples Molecular and cellular biology High 20679487
2011 VRK1 and VRK2 show differential sensitivity to kinase inhibitors; VRK2 is more sensitive to roscovitine, RO 31-8220, Cdk1 inhibitor, AZD7762, and IC261, while being poorly inhibited by most commonly used kinase inhibitors even at 100 µM, indicating a structurally distinct active site. In vitro kinase activity assay with panel of inhibitors PloS one Medium 21829721
2012 VRK2A forms a high molecular weight (600–1,000 kDa) stable complex with KSR1 and MEK1 anchored to the endoplasmic reticulum surface via direct C-terminal interactions between VRK2A and KSR1, and N-terminal VRK2A interactions with MEK1. This complex sequesters KSR1/MEK away from ERK1/2, preventing ERK incorporation after EGF stimulation. VRK2A knockdown disassembles these large complexes. Co-immunoprecipitation, size-exclusion chromatography, subcellular fractionation, siRNA knockdown, direct binding assays Cellular and molecular life sciences High 22752157
2012 VRK2 directly phosphorylates NFAT1 at Ser-32 within its N-terminal transactivation domain, increasing NFAT1-dependent transcription and COX-2 expression. This leads to enhanced tumor cell invasion, and VRK2A knockdown reduces COX-2 expression and invasion. In vitro kinase assay, co-immunoprecipitation, transcriptional reporter assay, siRNA knockdown, invasion assay The Journal of biological chemistry High 23105117
2017 VRK2 (but not VRK1) can complement vaccinia virus B1 kinase deletion for viral DNA replication, and this complementation is largely independent of BAF phosphorylation, suggesting VRK2 and B1 share additional substrates. VRK2 expression facilitates later stages of the viral life cycle in the absence of B1. VRK1/VRK2 knockout cell lines, B1-deletion vaccinia virus (vvΔB1), viral replication assays Journal of virology Medium 28515294
2018 VRK2 interacts with Akt1 and Akt2 (but not Akt3) at lysosomes during autophagy induction; the C-terminus of Akt and N-terminus of VRK2 mediate this interaction. VRK2A (but not VRK2B or kinase-dead VRK2A) facilitates lysosomal accumulation of phosphorylated Akt. VRK2 downregulation abrogates lysosomal Akt accumulation, impairs nuclear TFEB localization, and inhibits autophagy induction. TOF/MS, co-immunoprecipitation, bimolecular fluorescence complementation (BiFC), immunofluorescence, siRNA knockdown Oncogene High 29872222
2019 VRK2 (and B1) inhibit vaccinia virus B12 protein in a phosphorylation-dependent manner, and this inhibition is required for viral replication factory formation. VRK2 coprecipitates with B12, and kinase-dead VRK2 cannot inhibit B12 activity. Co-precipitation, kinase-dead mutant analysis, execution point analysis, viral replication assay in KO cells Journal of virology Medium 31341052
2021 VRK2 promotes mitochondrial stress-induced VDAC1 oligomerization and mtDNA release into the cytosol, activating the cGAS-mediated innate immune response. VRK2 associates with VDAC1 upon viral infection. VRK2 deficiency inhibits antiviral gene induction and causes higher mortality in mice after viral infection. Co-immunoprecipitation (VRK2-VDAC1 interaction), VDAC1 oligomerization assay, VRK2 KO mice, viral infection models, cGAS signaling readouts Cellular & molecular immunology High 33785841
2021 VRK2 is required for PD-1-induced phosphorylation of PAK2 and for PD-1-mediated inhibition of IL-2, IL-8, and IFN-γ secretion in T cells. Pharmacological or genetic inhibition of VRK2 combined with PD-1 blockade enhances tumor clearance in vivo. Phosphoproteomic analysis, shRNA knockdown, pharmacological inhibition, in vivo syngeneic tumor models Immunology letters Medium 33741379
2022 VRK1 and VRK2 are synthetic lethal paralogs in glioblastoma: VRK2 is silenced by promoter methylation in ~2/3 of GBM, and VRK1 knockdown in VRK2-null/methylated cells decreases BAF (barrier to autointegration factor) phosphorylation, causing nuclear lobulation, blebbing, micronucleation, G2-M arrest, and DNA damage. Ectopic VRK2 expression rescues VRK1 KD lethality. Genetic knockdown, ectopic expression rescue, BAF phosphorylation assay, nuclear morphology analysis, cell-line and patient-derived xenograft models Cancer research High 36069976
2022 VRK1 is a synthetic lethal target in VRK2-promoter-methylated gliomas and neuroblastomas; VRK1 depletion reduces BAF phosphorylation during mitosis, resulting in DNA damage and apoptosis specifically in VRK2-low cells. Genome-scale CRISPR/Cas9 screens, RNA-seq, VRK2 KO, BAF phosphorylation assay, in vivo xenograft JCI insight High 36040810
2022 VRK2 interacts with IKKβ and directly phosphorylates IKKβ at Ser177 and Ser181, thereby activating the TNFα/NF-κB signaling pathway and promoting pancreatic cancer growth. Co-immunoprecipitation, in vitro kinase assay, IKKβ inhibitor rescue experiments, tumor organoid and xenograft models International journal of biological sciences Medium 35173553
2023 VRK2 promotes phosphorylation of TKT (transketolase) at Thr287, which recruits FBXL6 to promote TKT ubiquitination and activation; activated TKT increases PD-L1 and VRK2 expression via ROS-mTOR, establishing a feed-forward oncogenic loop driving immune evasion and HCC metastasis. In vitro kinase assay (Thr287 phosphorylation), co-immunoprecipitation, ubiquitination assay, ROS measurement, mTOR pathway readouts, in vivo xenograft, IHC in patient samples Experimental & molecular medicine Medium 37653031
2023 VRK2-dependent phosphorylation of GAPDH at Ser151 is critical for GAPDH polyubiquitination by FBXW10 and subsequent activation; activated GAPDH interacts with TRAF2, upregulating canonical and noncanonical NF-κB pathways and increasing PD-L1 and AR-VRK2 expression, promoting male-specific HCC tumorigenesis. In vitro kinase assay, co-immunoprecipitation, ubiquitination assay, transgenic mouse models, NF-κB pathway readouts Cell reports Medium 37450367
2024 VRK2 interacts with VDAC2 and RACK1 at mitochondria; VRK2 inhibits IBDV-induced apoptosis by phosphorylating RACK1, thereby reducing viral replication. Overexpression of VRK2 reduces viral load, while VRK2 absence increases it. Co-immunoprecipitation, overexpression and knockdown, viral load quantification, apoptosis assay International journal of biological macromolecules Medium 39579830
2025 VRK2 directly phosphorylates MYC at Ser281 and Ser293, stabilizing the oncoprotein by competing with SCF-FBXO24 E3 ligase to block MYC polyubiquitination and proteasomal degradation. The stabilized MYC-VRK2 complex amplifies transcription of PD-L1 and VRK2 itself, creating a self-reinforcing oncogenic circuit in HCC. In vitro kinase assay (site-specific phosphorylation), co-immunoprecipitation, ubiquitination assay, proteasomal degradation assay, transcriptional reporter assay, VRK2 inhibitor treatment in tumor models Nature communications High 41073389
2025 RNF144A is upregulated by cellular stress (sodium arsenite, cisplatin) and promotes VRK2 proteasomal degradation. VRK2 phosphorylates G3BP1, and reduced VRK2 (and reduced G3BP1 phosphorylation) promotes stress granule assembly. Overexpression of VRK2 inhibits stress granule formation and sensitizes cells to chemotherapy. Co-immunoprecipitation, proteasomal degradation assay, in vitro kinase assay (G3BP1 phosphorylation), stress granule imaging, VRK2 overexpression/knockdown Cell death discovery Medium 40204710
2026 VRK2 is expressed specifically in microglia (not astrocytes) in the thalamus; microglial VRK2 loss reduces tonic GABA currents in the mediodorsal thalamus by altering cytokine signaling pathways. TNF-α inhibition or microglial depletion in wild-type mice recapitulates this deficit, indicating VRK2 maintains astrocytic GABA synthesis (via DAO-ALDH1A1 pathway) through microglial cytokine-dependent non-cell-autonomous signaling. Single-cell and bulk transcriptomics, Vrk2-deficient mice, electrophysiology (tonic GABA currents), pharmacological microglial depletion, TNF-α inhibition, astrocyte-specific interventions Glia Medium 41263186

Source papers

Stage 0 corpus · 41 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Common variants at VRK2 and TCF4 conferring risk of schizophrenia. Human molecular genetics 165 21791550
1997 Identification of two novel human putative serine/threonine kinases, VRK1 and VRK2, with structural similarity to vaccinia virus B1R kinase. Genomics 122 9344656
2006 The subcellular localization of vaccinia-related kinase-2 (VRK2) isoforms determines their different effect on p53 stability in tumour cell lines. The FEBS journal 69 16704422
2008 Modulation of interleukin-1 transcriptional response by the interaction between VRK2 and the JIP1 scaffold protein. PloS one 56 18286207
2021 VRK2 is involved in the innate antiviral response by promoting mitostress-induced mtDNA release. Cellular & molecular immunology 45 33785841
2012 Meta-analysis and brain imaging data support the involvement of VRK2 (rs2312147) in schizophrenia susceptibility. Schizophrenia research 44 23102693
2012 Human VRK2 (vaccinia-related kinase 2) modulates tumor cell invasion by hyperactivation of NFAT1 and expression of cyclooxygenase-2. The Journal of biological chemistry 40 23105117
2008 Proteomics identification of nuclear Ran GTPase as an inhibitor of human VRK1 and VRK2 (vaccinia-related kinase) activities. Molecular & cellular proteomics : MCP 39 18617507
2011 Differential inhibitor sensitivity between human kinases VRK1 and VRK2. PloS one 37 21829721
2010 VRK2 inhibits mitogen-activated protein kinase signaling and inversely correlates with ErbB2 in human breast cancer. Molecular and cellular biology 37 20679487
2018 VRK2, a Candidate Gene for Psychiatric and Neurological Disorders. Molecular neuropsychiatry 32 30643786
2022 VRK1 Is a Synthetic-Lethal Target in VRK2-Deficient Glioblastoma. Cancer research 31 36069976
2023 Elevated FBXL6 expression in hepatocytes activates VRK2-transketolase-ROS-mTOR-mediated immune evasion and liver cancer metastasis in mice. Experimental & molecular medicine 28 37653031
2012 VRK2 anchors KSR1-MEK1 to endoplasmic reticulum forming a macromolecular complex that compartmentalizes MAPK signaling. Cellular and molecular life sciences : CMLS 28 22752157
2006 Human cellular protein VRK2 interacts specifically with Epstein-Barr virus BHRF1, a homologue of Bcl-2, and enhances cell survival. The Journal of general virology 25 16963744
2018 Functional characterization of lysosomal interaction of Akt with VRK2. Oncogene 24 29872222
2008 The C/H3 domain of p300 is required to protect VRK1 and VRK2 from their downregulation induced by p53. PloS one 23 18612383
2022 VRK1 as a synthetic lethal target in VRK2 promoter-methylated cancers of the nervous system. JCI insight 21 36040810
2017 Deletion of the Vaccinia Virus B1 Kinase Reveals Essential Functions of This Enzyme Complemented Partly by the Homologous Cellular Kinase VRK2. Journal of virology 18 28515294
2023 Elevated FBXW10 drives hepatocellular carcinoma tumorigenesis via AR-VRK2 phosphorylation-dependent GAPDH ubiquitination in male transgenic mice. Cell reports 17 37450367
2022 VRK2 activates TNFα/NF-κB signaling by phosphorylating IKKβ in pancreatic cancer. International journal of biological sciences 17 35173553
2017 Vaccinia Related Kinase 2 (VRK2) expression in neurological disorders: schizophrenia, epilepsy and multiple sclerosis. Multiple sclerosis and related disorders 16 29100046
2015 Association of the VRK2 gene rs3732136 polymorphism with schizophrenia in a Northwest Chinese Han population. Genetics and molecular research : GMR 15 26345874
2014 Effects of VRK2 (rs2312147) on white matter connectivity in patients with schizophrenia. PloS one 14 25079070
2016 Further evidence of VRK2 rs2312147 associated with schizophrenia. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry 10 27382989
2023 Reduced Vrk2 expression is associated with higher risk of depression in humans and mediates depressive-like behaviors in mice. BMC medicine 8 37452335
2021 VRK2 inhibition synergizes with PD-1 blockade to improve T cell responses. Immunology letters 8 33741379
2022 Vrk2 deficiency elicits aggressive behavior in female zebrafish. Genes to cells : devoted to molecular & cellular mechanisms 7 35094457
2019 The Vaccinia Virus (VACV) B1 and Cellular VRK2 Kinases Promote VACV Replication Factory Formation through Phosphorylation-Dependent Inhibition of VACV B12. Journal of virology 6 31341052
2020 Novel alternatively-spliced exons of the VRK2 gene in mouse brain and microglial cells. Molecular biology reports 5 32583282
2021 Blocking VRK2 suppresses pulmonary adenocarcinoma progression via ERK1/2/AKT signal pathway by targeting miR-145-5p. European review for medical and pharmacological sciences 3 33506902
2025 VRK2 promotes colorectal cancer growth and impedes immunotherapy and 5-FU treatment efficacy. Biochimica et biophysica acta. Molecular basis of disease 2 39978443
2021 Blocking VRK2 suppresses pulmonary adenocarcinoma progression via ERK1/2/AKT signal pathway by targeting miR-145-5p. European review for medical and pharmacological sciences 2 34156669
2026 Microglial VRK2 Regulates Astrocytic GABA Synthesis and Tonic Inhibition in the Thalamus. Glia 1 41263186
2025 RNF144A-VRK2-G3BP1 axis regulates stress granule assembly. Cell death discovery 1 40204710
2025 VRK2 targeting potentiates anti-PD-1 immunotherapy in hepatocellular carcinoma through MYC destabilization. Nature communications 1 41073389
2024 VRK2 inhibits the replication of infectious bursal disease virus by phosphorylating RACK1 and suppressing apoptosis. International journal of biological macromolecules 1 39579830
2021 Data on the identification of VRK2 as a mediator of PD-1 function. Data in brief 1 34113705
2025 VRK2 kinase pathogenic pathways in cancer and neurological diseases. Biochimica et biophysica acta. Molecular cell research 0 40187568
2025 The complex association of VRK2 with major depressive disorder in Han Chinese population. Journal of affective disorders 0 40294824
2021 Evaluation of the relationship between VRK2, rs4380187 polymorphisms, and genetic susceptibility to schizophrenia in the Chinese Han population. The journal of gene medicine 0 33522046