CK2 activity is crucial for proper glucagon expression.

Aims/hypothesis: Protein kinase CK2 acts as a negative regulator of insulin expression in pancreatic beta cells. This action is mainly mediated by phosphorylation of the transcription factor pancreatic and duodenal homeobox protein 1 (PDX1). In pancreatic alpha cells, PDX1 acts in a reciprocal fashion on glucagon (GCG) expression.

Protein Kinase CK2α', More than a Backup of CK2α.

The serine/threonine protein kinase CK2 is implicated in the regulation of fundamental processes in eukaryotic cells. CK2 consists of two catalytic α or α' isoforms and two regulatory CK2β subunits. These three proteins exist in a free form, bound to other cellular proteins, as tetrameric holoenzymes composed of CK2α/β, CK2αα'/β, or CK2α'/β as well as in higher molecular forms of the tetramers.

Protein Kinase CK2 and Epstein-Barr Virus.

Protein kinase CK2 is a pleiotropic protein kinase, which phosphorylates a number of cellular and viral proteins. Thereby, this kinase is implicated in the regulation of cellular signaling, controlling of cell proliferation, apoptosis, angiogenesis, immune response, migration and invasion. In general, viruses use host signaling mechanisms for the replication of their genome as well as for cell transformation leading to cancer.

Protein Kinase CK2 Contributes to Glucose Homeostasis by Targeting Fructose-1,6-Bisphosphatase 1.

Glucose homeostasis is of critical importance for the survival of organisms. It is under hormonal control and often coordinated by the action of kinases and phosphatases. We have previously shown that CK2 regulates insulin production and secretion in pancreatic β-cells.

Inhibition of CK2 Reduces NG2 Expression in Juvenile Angiofibroma.

Juvenile angiofibroma (JA) is a rare fibrovascular neoplasm predominately found within the posterior nasal cavity of adolescent males. JA expresses the proteoglycan nerve-glial antigen (NG)2, which crucially determines the migratory capacity of distinct cancer cells. Moreover, it is known that the protein kinase CK2 regulates NG2 gene expression.

SGC-CK2-1 Is an Efficient Inducer of Insulin Production and Secretion in Pancreatic β-Cells.

The pyrazolopyrimidine based compound SGC-CK2-1 is a potent and highly specific CK2 inhibitor and a new tool to study the biological functions of protein kinase CK2 irrespective from off-target effects. We used this compound in comparison with the well-established CK2 inhibitor CX-4945 to analyze the importance of CK2 for insulin production and secretion from pancreatic β-cells. Both inhibitors affected the proliferation and viability of MIN6 cells only marginally and downregulated the endogenous CK2 activity to a similar level.

Control of TRPM3 Ion Channels by Protein Kinase CK2-Mediated Phosphorylation in Pancreatic β-Cells of the Line INS-1.

In pancreatic β-cells of the line INS-1, glucose uptake and metabolism induce the openings of Ca-permeable TRPM3 channels that contribute to the elevation of the intracellular Ca concentration and the fusion of insulin granules with the plasma membrane. Conversely, glucose-induced Ca signals and insulin release are reduced by the activity of the serine/threonine kinase CK2. Therefore, we hypothesized that TRPM3 channels might be regulated by CK2 phosphorylation.

Protein kinase CK2 and ion channels (Review).

Protein kinase CK2 appears as a tetramer or higher molecular weight oligomer composed of catalytic CK2α, CK2α' subunits and non-catalytic regulatory CK2β subunits or as individual subunits. It is implicated in a variety of different regulatory processes, such as Akt signalling, splicing and DNA repair within eukaryotic cells. The present review evaluates the influence of CK2 on ion channels in the plasma membrane.

Protein Kinase CK2 Controls Ca2.1-Dependent Calcium Currents and Insulin Release in Pancreatic β-Cells.

The regulation of insulin biosynthesis and secretion in pancreatic β-cells is essential for glucose homeostasis in humans. Previous findings point to the highly conserved, ubiquitously expressed serine/threonine kinase CK2 as having a negative regulatory impact on this regulation. In the cell culture model of rat pancreatic β-cells INS-1, insulin secretion is enhanced after CK2 inhibition.

The stability of CREB3/Luman is regulated by protein kinase CK2 phosphorylation.

CREB3 (Luman) is a family member of ER resident transcription factors, which are cleaved upon the induction of ER stress. Their N-terminal fragments shuttle into the nucleus where they regulate the transcription of target genes. Here, we found that human CREB3 is phosphorylated within its transcription activation domain on serine 46 by protein kinase CK2.

Protein Kinase CK2-A Putative Target for the Therapy of Diabetes Mellitus?

Since diabetes is a global epidemic, the development of novel therapeutic strategies for the treatment of this disease is of major clinical interest. Diabetes is differentiated in two types: type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). T1DM arises from an autoimmune destruction of insulin-producing β-cells whereas T2DM is characterized by an insulin resistance, an impaired insulin reaction of the target cells, and/or dysregulated insulin secretion.

Influence of cryopreservation on the 2 and expression levels and protein levels in human spermatozoa.

This study designed to assess the expression level of and to evaluate the levels of CatSper2 and Tektin2 proteins in human spermatozoa before and after cryopreservation. One hundred and twenty semen samples were included in this study. All the samples were subjected to qPCR and Western blot analysis.

The status of global DNA methylation in the spermatozoa of smokers and non-smokers.

Research Question: Does regular smoking affect semen quality and the levels of DNA methylation in mature human spermatozoa?

Design: Spermatozoa from 109 men were evaluated (55 smokers and 54 non-smokers). DNA was extracted from purified spermatozoa, and DNA methylation was quantified by enzyme-linked immunosorbent assay (ELISA).

Results: Global DNA methylation of non-smokers is significantly lower (P < 0.

Ecto-protein kinase CK2, the neglected form of CK2.

Ecto-protein kinases, including protein kinase CK2 (former name, casein kinase 2), have been the focus of research for more than 30 years. At the beginning of the ecto-kinase research their identification was performed with substrates and inhibitors whose specificity under the current knowledge was rather limited. Since all currently known ecto-kinases, including ecto-CK2, have intracellular counterparts, one has to exclude that an ecto-localization originates from intracellular counterparts after cell damage.

Functional interplay between the transcription factors USF1 and PDX-1 and protein kinase CK2 in pancreatic β-cells.

Glucose homeostasis is regulated by insulin, which is produced in the β-cells of the pancreas. The synthesis of insulin is controlled by several transcription factors including PDX-1, USF1 and USF2. Both, PDX-1 and USF1 were identified as substrates for protein kinase CK2.

The impact of cigarette smoking on protamines 1 and 2 transcripts in human spermatozoa.

This study was conducted to evaluate the relation between cigarette smoking, semen quality and ratios of protamine mRNAs in smokers and non-smokers. Spermatozoa from 123 men and 64 smokers and 59 non-smokers whose female partners attended an assisted reproduction and andrology laboratory were evaluated. Protamine mRNA was extracted from purified sperm, reverse-transcribed and subjected to real-time quantitative PCR using specific primer pairs for protamine 1 (PRM1) and protamine 2 (PRM2).

Quinalizarin inhibits adipogenesis through down-regulation of transcription factors and microRNA modulation.

Background: Protein kinase CK2 is induced early in adipogenesis whereas later on, this kinase seems to be dispensable. Here, we have analysed how CK2 might be involved in early steps of differentiation of 3T3-L1 cells.

Methods: 3T3-L1 cells were differentiated to adipocytes in the absence or presence of quinalizarin.

Impact of protein kinase CK2 inhibitors on proliferation and differentiation of neural stem cells.

Background: Protein kinases play central roles in cell and tissue development. Protein kinase CK2, an ubiquitously expressed serine/threonine kinase has severe impacts on embryo- and spermatogenesis. Since its role in neurogenesis has so far only been investigated in very few studies, we analysed the role of CK2 in neural stem cells by using two specific inhibitors.

The mammalian STE20-like kinase 1 (MST1) is a substrate for the apoptosis inhibiting protein kinase CK2.

Apoptosis and the response to cell stress are evolutionary highly conserved mechanisms. Both processes require strict regulation, which is often performed by protein kinases. The mammalian Sterile 20-like kinase 1 (MST1) is a pro-apoptotic protein kinase, which is activated and cleaved by caspases upon the induction of cell stress.

Novel coumarin- and quinolinone-based polycycles as cell division cycle 25-A and -C phosphatases inhibitors induce proliferation arrest and apoptosis in cancer cells.

Cell division cycle phosphatases CDC25 A, B and C are involved in modulating cell cycle processes and are found overexpressed in a large panel of cancer typology. Here, we describe the development of two novel quinone-polycycle series of CDC25A and C inhibitors on the one hand 1a-k, coumarin-based, and on the other 2a-g, quinolinone-based, which inhibit either enzymes up to a sub-micro molar level and at single-digit micro molar concentrations, respectively. When tested in six different cancer cell lines, compound 2c displayed the highest efficacy to arrest cell viability, showing in almost all cell lines sub-micro molar IC values, a profile even better than the reference compound NCS95397.

Protein kinase CK2 in development and differentiation.

Among the human kinomes, protein kinase CK2 (formerly termed casein kinase II) is considered to be essential, as it is implicated in the regulation of various cellular processes. Experiments with pharmacological inhibitors of the kinase activity of CK2 provide evidence that CK2 is essential for development and differentiation. Therefore, the present review addresses the role of CK2 during embryogenesis, neuronal, adipogenic, osteogenic and myogenic differentiation in established model cell lines, and in embryonic, neural and mesenchymal stem cells.

An Updated View on an Emerging Target: Selected Papers from the 8th International Conference on Protein Kinase CK2.

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Inhibition of Protein Kinase CK2 Prevents Adipogenic Differentiation of Mesenchymal Stem Cells Like C3H/10T1/2 Cells.

Protein kinase CK2 as a holoenzyme is composed of two catalytic α- or α'-subunits and two non-catalytic β-subunits. Knock-out experiments revealed that CK2α and CK2β are required for embryonic development. Little is known about the role of CK2 during differentiation of stem cells.

The Phosphorylation of PDX-1 by Protein Kinase CK2 Is Crucial for Its Stability.

The homeodomain protein PDX-1 is a critical regulator of pancreatic development and insulin production in pancreatic β-cells. We have recently shown that PDX-1 is a substrate of protein kinase CK2; a multifunctional protein kinase which is implicated in the regulation of various cellular aspects, such as differentiation, proliferation, and survival. The CK2 phosphorylation site of PDX-1 is located within the binding region of the E3 ubiquitin ligase adaptor protein PCIF1.

Protein Kinase CK2 Regulates Leukocyte-Endothelial Cell Interactions during Ischemia and Reperfusion in Striated Skin Muscle.

Background: Ischemia and reperfusion (I/R) causes tissue injury by inflammatory processes. This involves the upregulation of endothelial surface proteins by phospho-regulated signaling pathways, resulting in enhanced interactions of leukocytes with endothelial cells. Recently, we found that protein kinase CK2 is a crucial regulator of leukocyte-mediated inflammation.