ArticleThe Journal of biological chemistry2012
Human VRK2 (vaccinia-related kinase 2) modulates tumor cell invasion by hyperactivation of NFAT1 and expression of cyclooxygenase-2.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Metabolic modeling and functional genomics reveal taxa and host gene interactions in colorectal cancer.bioRxiv : the preprint server for biology · 2026Article
- Microglial VRK2 Regulates Astrocytic GABA Synthesis and Tonic Inhibition in the Thalamus.Glia · 2026Article
- DNA methylation and bronchiectasis: a Mendelian randomization analysis to investigate causal link and therapeutic target.Epigenetics · 2025Article
- VRK2 targeting potentiates anti-PD-1 immunotherapy in hepatocellular carcinoma through MYC destabilization.Nature communications · 2025Article
- RNF144A-VRK2-G3BP1 axis regulates stress granule assembly.Cell death discovery · 2025Article
- Elevated FBXL6 expression in hepatocytes activates VRK2-transketolase-ROS-mTOR-mediated immune evasion and liver cancer metastasis in mice.Experimental & molecular medicine · 2023Article
- Vaccinia-related kinase 2 variants differentially affect breast cancer growth by regulating kinase activity.Oncology research · 2023Article
- Differentially Expressed Genes in Nasopharyngeal Carcinoma Tissues and Their Correlation with Recurrence and Metastasis of Nasopharyngeal Carcinoma.Computational and mathematical methods in medicine · 2022Article
- VRK1 Predicts Poor Prognosis and Promotes Bladder Cancer Growth and MetastasisFrontiers in pharmacology · 2022Article
- VRK2 activates TNFα/NF-κB signaling by phosphorylating IKKβ in pancreatic cancer.International journal of biological sciences · 2022Article
- Combination Approaches to Target PD-1 Signaling in Cancer.Frontiers in immunology · 2022Review
- Vaccinia-related kinase 2 drives pancreatic cancer progression by protecting Plk1 from Chfr-mediated degradation.Oncogene · 2021Article
- Occurrence of Accelerated Epigenetic Aging and Methylation Disruptions in Human Immunodeficiency Virus Infection Before Antiretroviral Therapy.The Journal of infectious diseases · 2021Article
- VRK2 is involved in the innate antiviral response by promoting mitostress-induced mtDNA release.Cellular & molecular immunology · 2021Article
- VRK2 inhibition synergizes with PD-1 blockade to improve T cell responses.Immunology letters · 2021Article
- Vaccinia-related kinase 2 blunts sorafenib's efficacy against hepatocellular carcinoma by disturbing the apoptosis-autophagy balance.Oncogene · 2021Article
- The Trinity of Matrix Metalloproteinases, Inflammation, and Cancer: A Literature Review of Recent Updates.Anti-inflammatory & anti-allergy agents in medicinal chemistry · 2020Review
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human VRK2 (vaccinia-related kinase 2), a kinase that emerged late in evolution, affects different signaling pathways, and some carcinomas express high levels of VRK2. Invasion by cancer cells has been associated with NFAT1 (nuclear factor of activated T cells) activation and expression of the COX-2 (cyclooxygenase 2) gene. We hypothesized that VRK proteins might play a regulatory role in NFAT1 activation in tumor cells. We demonstrate that VRK2 directly interacts and phosphorylates NFAT1 in Ser-32 within its N-terminal transactivation domain. VRK2 increases NFAT1-dependent transcription by phosphorylation, and this effect is only detected following cell phorbol 12-myristate 13-acetate and ionomycin stimulation and calcineurin activation. This NFAT1 hyperactivation by VRK2 increases COX-2 gene expression through the proximal NFAT1 binding site in the COX-2 gene promoter. Furthermore, VRK2A down-regulation by RNA interference reduces COX-2 expression at transcriptional and protein levels. Therefore, VRK2 down-regulation reduces cell invasion by tumor cells, such as MDA-MB-231 and MDA-MB-435, upon stimulation with phorbol 12-myristate 13-acetate plus ionomycin. These findings identify the first reported target and function of human VRK2 as an active kinase playing a role in regulation of cancer cell invasion through the NFAT pathway and COX-2 expression.
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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.