Protein Kinase 2 (CK2) Controls CD4+ T-cell Effector Function in the Pathogenesis of Colitis
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ABSTRACT:
PROVIDER: PRJNA545474 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9160371.fastq.gz | Fastqsanger.gz | |||
| SRR9160371_1.fastq.gz | Fastqsanger.gz | |||
| SRR9160371_2.fastq.gz | Fastqsanger.gz | |||
| SRR9160372.fastq.gz | Fastqsanger.gz | |||
| SRR9160372_1.fastq.gz | Fastqsanger.gz |
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Project description:Crohn’s disease (CD) is one of the major forms of inflammatory bowel disease (IBD), characterized by chronic inflammation of the gastrointestinal tract. CD is associated with aberrant Th1 and Th17 responses accompanied by high levels of IFN-g and IL-17, respectively. Protein kinase 2 (CK2) is a highly conserved serine-threonine kinase that is involved in several signal transduction pathways which regulate inflammatory responses. CK2 promotes Th17 cell differentiation and suppresses the generation of Foxp3+ regulatory T cells. The function of CK2 in CD4+ T-cells during the pathogenesis of CD is unknown. We utilized T-cell induced colitis model, transferring CD45RBhi naïve CD4+ T-cells from CK2afl/fl littermate control and CK2afl/fldLck-Cre mice into Rag1-/- mice. We demonstrate that CD4+ T-cells from CK2afl/fldLck-Cre mice fail to induce wasting disease and significant intestinal inflammation, which is associated with decreased IL-17A+, IFN-g+ and double positive IL-17A+ IFN-g+ CD4+ T-cells in the spleen and colon. Further, we determine that CK2a regulates CD4+ T-cell proliferation through a cell-intrinsic manner. CK2a is also important in controlling CD4+ T-cell responses by regulating NFAT2, which is vital for T-cell activation and proliferation. Thus, our data demonstrate that CK2a contributes to the pathogenesis of colitis by promoting CD4+ T-cell proliferation and Th1 and Th17 responses, and that targeting CK2 kinase activity may be a novel therapeutic treatment for CD patients.
2020-08-05 | GSE131965 | GEO
Project description:Protein kinase 2 (CK2) is a serine/threonine kinase composed of two catalytic subunits (CK2α and/or CK2α') and two regulatory subunits (CK2β). CK2 has been shown to promote cancer progression by regulating the NF-κB, PI3K/AKT/mTOR, JAK/STAT and HIF-1α pathways, and also plays a critical role for immune cell development and function. However, the potential involvement of CK2 in CD8+ T-cell function has not explored. Here, we demonstrate that CK2 protein levels and kinase activity are enhanced upon CD8+ T-cell activation. CK2α deficiency results in impaired CD8+ T-cell activation and proliferation upon TCR stimulation. Furthermore, CK2α is involved in CD8+ T-cell metabolic reprogramming during activation through regulating the AKT/mTOR signaling pathway. Lastly, using a Listeria monocytogenes infection model, we demonstrate that CK2α is required for CD8+ T-cell expansion, maintenance and effector function in both primary and memory immune responses. Taken together, our study implicates CK2 as an important regulator of CD8+ T-cell activation and differentiation both in vitro and in vivo.
2022-06-21 | GSE175941 | GEO
Project description:Protein Kinase 2 (CK2) Controls CD8+ T-cell Effector and Memory Function during Infection
| PRJNA734332 | ENA
Project description:Crohn's disease (CD), one of the major forms of inflammatory bowel disease (IBD), is characterized by chronic inflammation of the gastrointestinal tract and associated with aberrant CD4+ T-helper type 1 (Th1) and Th17 responses. Protein kinase 2 (CK2) is a conserved serine-threonine kinase involved in signal transduction pathways, which regulate immune responses. CK2 promotes Th17 cell differentiation and suppresses the generation of Foxp3+ regulatory T cells. The function of CK2 in CD4+ T cells during the pathogenesis of CD is unknown. We utilized the T cell-induced colitis model, transferring CD45RBhi-naive CD4+ T cells from CK2αfl/fl controls and CK2αfl/fldLck-Cre mice into Rag1-/- mice. CD4+ T cells from CK2αfl/fldLck-Cre mice failed to induce wasting disease and significant intestinal inflammation, which was associated with decreased interleukin-17A-positive (IL-17A+), interferon-γ-positive (IFN-γ+), and double-positive IL-17A+IFN-γ+ CD4+ T cells in the spleen and colon. We determined that CK2α regulates CD4+ T cell proliferation through a cell-intrinsic manner. CK2α is also important in controlling CD4+ T cell responses by regulating NFAT2, which is vital for T cell activation and proliferation. Our findings indicate that CK2α contributes to the pathogenesis of colitis by promoting CD4+ T cell proliferation and Th1 and Th17 responses, and that targeting CK2 may be a novel therapeutic treatment for patients with CD.
| S-EPMC7382987 | biostudies-literature
Project description:Protein Ser/Thr kinase CK2 is involved in a myriad of cellular processes including cell growth and proliferation by phosphorylating hundreds of substrates, yet the regulation process of CK2 function is poorly understood. The CK2 catalytic subunit, CK2α, is modified by O-GlcNAc on Ser347 proximal to a Cdk1 phosphorylation site at Thr344 on the same protein. The substrate selectivity for protein kinase CK2 was examined by performing kinase assays on protein microarrays spotted with 17,000 human proteins. Semisynthetic CK2α proteins were prepared to contain an unmodified C-terminal tail, S-GlcNAc-Serine at S347, or Pfa (non-hyrdolyzeable phosphomimic) at T344. These semisynthetic proteins were used to determine if the posttranslational modifications on CK2 alpha modulate the substrate selectivity for this pleiotropic kinase. The different semisynthetic CK2α proteins were tested alone and in the presence of the regulatory subunit CK2β since it is known that the CK2α subunit is active both in its isolated state and in the heterotetrameric state formed in the presence of the regulatory beta subunit. The CK2β subunit has been shown to modulate CK2 activity with some substrates and not others. In the study presented here, kinase assays were performed using three different semisynthetic CK2 alpha proteins: unmodified C-terminal tail; S-GlcNAc-Ser at 347; and Pfa (phosphomimic) at 344. The semisynthetic proteins were each tested alone and in the presence of the regualatory CK2 beta subunit. There were six different kinase conditions and each condition was performed in duplicate and one no kinase control was performed to eliminate autophorylated proteins.
2011-10-24 | E-GEOD-33149 | biostudies-arrayexpress
Project description:Maf-family basic motif leucine zipper protein NRL specifies rod photoreceptor cell fate during retinal development and, in concert with homeodomain protein CRX and other regulatory factors, controls the expression of most rod-expressed genes including the visual pigment gene RHO (rhodopsin). Transcriptional regulatory activity of NRL is modulated by post-translational modifications (PTMs), specially phosphorylation, and mutations in phosphosites can lead to retinal degeneration. During our studies to elucidate NRL-mediated transcriptional regulation, we identified Protein Kinase CK2 in NRL-enriched complexes bound to RHO promoter-enhancer regions and in NRL-enriched high molecular mass fractions from the bovine retina. The presence of CK2 in NRL complexes was confirmed by co-immunoprecipitation from developing and adult mouse retinal extracts. Bioinformatic and mass spectrometry analysis indicated potential phosphorylation of NRL at Ser117 residue by CK2. Co-transfection of Csnk2a1 cDNA encoding CK2 with NRL and CRX reduced the bovine Rho promoter-driven luciferase expression in HEK293 cells, and mutagenesis of NRL-Ser117 residue to Ala restored the reporter gene expression. In concordance, overexpression of CK2 in the mouse retina in vivo by electroporation resulted in reduction of Rho promoter-driven DsRed reporter gene expression. RNA-seq analysis of CK2-electroporated retina revealed altered expression of many transcriptional targets of NRL. Thus, our studies demonstrate an important role of CK2 in context-dependent fine-tuning of NRL function, consequently modulating the expression of rod photoreceptor genes.
2024-04-06 | GSE171665 | GEO
Project description:Protein Ser/Thr kinase CK2 is involved in a myriad of cellular processes including cell growth and proliferation by phosphorylating hundreds of substrates, yet the regulation process of CK2 function is poorly understood. The CK2 catalytic subunit, CK2α, is modified by O-GlcNAc on Ser347 proximal to a Cdk1 phosphorylation site at Thr344 on the same protein. The substrate selectivity for protein kinase CK2 was examined by performing kinase assays on protein microarrays spotted with 17,000 human proteins. Semisynthetic CK2α proteins were prepared to contain an unmodified C-terminal tail, S-GlcNAc-Serine at S347, or Pfa (non-hyrdolyzeable phosphomimic) at T344. These semisynthetic proteins were used to determine if the posttranslational modifications on CK2 alpha modulate the substrate selectivity for this pleiotropic kinase. The different semisynthetic CK2α proteins were tested alone and in the presence of the regulatory subunit CK2β since it is known that the CK2α subunit is active both in its isolated state and in the heterotetrameric state formed in the presence of the regulatory beta subunit. The CK2β subunit has been shown to modulate CK2 activity with some substrates and not others.
2011-10-25 | GSE33149 | GEO
Project description:Protein Ser/Thr kinase CK2 is involved in a myriad of cellular processes including cell growth and proliferation by phosphorylating hundreds of substrates, yet the regulation process of CK2 function is poorly understood. The CK2 catalytic subunit, CK2α, is phosphorylated at Thr344 and phosphorylation on the C-terminal tail of CK2α is required for interaction with Pin1 protein. The substrate selectivity for protein kinase CK2α was examined by performing kinase assays on protein microarrays spotted with 17,000 human proteins. Semisynthetic CK2α proteins were prepared to contain an unmodified C-terminal tail or phospho-Thr (pThr) at T344. These semisynthetic proteins were used to determine if the phosphorylation-dependent interaction of CK2α with Pin1 can modulate the substrate selectivity for CK2. The different semisynthetic CK2α proteins (unmodified and pThr344) were tested alone and in the presence of the recombinant Pin1 protein. Pin1 has been shown to interaction with CK2α only when CK2α is phoshorylated on its C-terminal site (including Thr344). In the study presented here, kinase assays were performed using two different semisynthetic CK2α proteins: unmodified C-terminal tail and phospho-Thr (pThr) at 344. The semisynthetic proteins were each tested alone and in the presence of the recombinant Pin1 protein. There were four different kinase conditions and each condition was performed in duplicate.
2011-10-24 | E-GEOD-33150 | biostudies-arrayexpress
Project description:We report that CK2 inhibition with CX-4945 broadly suppresses Th17-associated effector and metabolic gene expression. CD4+ T cells were cultured in IL-6, IL-23 and TGFb1 for 72 h, in the absence of presence of 2 mM CX-4945, RNA-seq was performed and gene expression compared between the control and treatment groups.
2017-05-05 | GSE86976 | GEO
Project description:Protein Ser/Thr kinase CK2 is involved in a myriad of cellular processes including cell growth and proliferation by phosphorylating hundreds of substrates, yet the regulation process of CK2 function is poorly understood. The CK2 catalytic subunit, CK2α, is phosphorylated at Thr344 and phosphorylation on the C-terminal tail of CK2α is required for interaction with Pin1 protein. The substrate selectivity for protein kinase CK2α was examined by performing kinase assays on protein microarrays spotted with 17,000 human proteins. Semisynthetic CK2α proteins were prepared to contain an unmodified C-terminal tail or phospho-Thr (pThr) at T344. These semisynthetic proteins were used to determine if the phosphorylation-dependent interaction of CK2α with Pin1 can modulate the substrate selectivity for CK2. The different semisynthetic CK2α proteins (unmodified and pThr344) were tested alone and in the presence of the recombinant Pin1 protein. Pin1 has been shown to interaction with CK2α only when CK2α is phoshorylated on its C-terminal site (including Thr344).
2011-10-25 | GSE33150 | GEO