ArticlePloS one2008
Modulation of interleukin-1 transcriptional response by the interaction between VRK2 and the JIP1 scaffold protein.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Common variants at VRK2 and TCF4 conferring risk of schizophrenia.Human molecular genetics · 2011Pooled it
- Emergence of Catalytic Activity in VRK3: Phosphoproteomic Insights into the Regulatory Network of a Former Pseudokinase.Proteomes · 2026Review
- Gene-by-Sleep Duration Interaction for Glycemic Traits in over 480,000 Individuals.medRxiv : the preprint server for health sciences · 2026Article
- Combination Approaches to Target PD-1 Signaling in Cancer.Frontiers in immunology · 2022Review
- Purification, characterization and functional site prediction of the vaccinia-related kinase 2A small transmembrane domain.MethodsX · 2022Article
- VRK2 inhibition synergizes with PD-1 blockade to improve T cell responses.Immunology letters · 2021Article
- VRK2 is involved in the innate antiviral response by promoting mitostress-induced mtDNA release.Cellular & molecular immunology · 2021Article
- Novel alternatively-spliced exons of the VRK2 gene in mouse brain and microglial cells.Molecular biology reports · 2020Article
- Molecular dissection of Chagas induced cardiomyopathy reveals central disease associated and druggable signaling pathways.PLoS neglected tropical diseases · 2020Article
- Profiling of differentially expressed circular RNAs in peripheral blood mononuclear cells from Alzheimer's disease patients.Metabolic brain disease · 2020Article
- Review
- Article
- DUSP1 regulates apoptosis and cell migration, but not the JIP1-protected cytokine response, during Respiratory Syncytial Virus and Sendai Virus infection.Scientific reports · 2017Article
- Structural characterization of human Vaccinia-Related Kinases (VRK) bound to small-molecule inhibitors identifies different P-loop conformations.Scientific reports · 2017Article
- Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population.Molecular psychiatry · 2017Article
- Identification of Multiple Forms of RNA Transcripts Associated with Human-Specific Retrotransposed Gene Copies.Genome biology and evolution · 2016Article
- Predictive value of vrk 1 and 2 for rectal adenocarcinoma response to neoadjuvant chemoradiation therapy: a retrospective observational cohort study.BMC cancer · 2016Article
- Oncogenic Sox2 regulates and cooperates with VRK1 in cell cycle progression and differentiation.Scientific reports · 2016Article
- Vaccinia-related kinase 1 (VRK1) confers resistance to DNA-damaging agents in human breast cancer by affecting DNA damage response.Oncotarget · 2014Article
- Effects of VRK2 (rs2312147) on white matter connectivity in patients with schizophrenia.PloS one · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCellular biological responses to specific stimulation are determined by a balance among signaling pathways. Protein interactions are likely to modulate these pathways. Vaccinia-related kinase-2 (VRK2) is a novel human kinase that can modulate different signaling pathways. PRINCIPAL
findingsWe report that in vivo, the activity of JIP1-JNK complexes is downregulated by VRK2 in response to interleukin-1beta. Also the reduction of endogenous VRK2 with shRNA increases the transcriptional response to IL-1beta. The JIP1 scaffold protein assembles three consecutive members of a given MAPK pathway forming signaling complexes and their signal can be modulated by interactions with regulatory proteins that remain to be identified. Knocking-down JIP1 with siRNA resulted in elimination of the AP1 transcriptional response to IL-1beta. VRK2, a member of novel Ser-Thr kinase family, is able to stably interact with JIP1, TAK1 and MKK7, but not JNK, and can be isolated forming oligomeric complexes with different proportions of TAK1, MKK7beta1 and JNK. JIP1 assembles all these proteins in an oligomeric signalosome. VRK2 binding to the JIP1 signalosome prevents the association of JNK and results in a reduction in its phosphorylation and downregulation of AP1-dependent transcription. CONCLUSIONS/SIGNIFICANCE: This work suggests that the intracellular level of VRK2 protein can modulate the flow through a signaling pathway and alter the response from a receptor that can be distributed by more than one pathway, and thus contribute to the cellular specificity of the response by forming alternative signaling complexes. Furthermore, the effect might be more general and affect other signaling routes assembled on the JIP1 scaffold protein for which a model is proposed.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.