122 research outputs found
Hadronic gas models in particle production and phase transitions
In this work the methods of exact quantum number conservation in statistical mechanics are discussed and applied to the field of high energy nucleus-nucleus collisions. Various types of hadronic gas models are discussed as well as their merits and restrictions. Attempts to construct a phenomenological equation of state for nuclear matter are discussed in the context of the phase transition from hadronic matter to the quark-gluon plasma (QGP)
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 CK2α2/β2
, CK2αα’/β2
, or CK2α’2/β2 as well as in higher molecular
forms of the tetramers. The catalytic domains of CK2α and CK2α’ share a 90% identity. As CK2α
contains a unique C-terminal sequence. Both proteins function as protein kinases. These properties
raised the question of whether both isoforms are just backups of each other or whether they are
regulated differently and may then function in an isoform-specific manner. The present review
provides observations that the regulation of both CK2α isoforms is partly different concerning the
subcellular localization, post-translational modifications, and aggregation. Up to now, there are only
a few isoform-specific cellular binding partners. The expression of both CK2α isoforms seems to
vary in different cell lines, in tissues, in the cell cycle, and with differentiation. There are different
reports about the expression and the functions of the CK2α isoforms in tumor cells and tissues. In
many cases, a cell-type-specific expression and function is known, which raises the question about
cell-specific regulators of both isoforms. Another future challenge is the identification or design of
CK2α’-specific inhibitors
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. Therefore, it is not surprising that CK2 also plays a role in
controlling viral infection and the generation of cancer cells. Epstein–Barr virus (EBV) lytically infects
epithelial cells of the oropharynx and B cells. These latently infected B cells subsequently become
resting memory B cells when passing the germinal center. Importantly, EBV is responsible for the
generation of tumors such as Burkitt’s lymphoma. EBV was one of the first human viruses, which
was connected to CK2 in the early nineties of the last century. The present review shows that protein
kinase CK2 phosphorylates EBV encoded proteins as well as cellular proteins, which are implicated
in the lytic and persistent infection and in EBV-induced neoplastic transformation. EBV-encoded and
CK2-phosphorylated proteins together with CK2-phosphorylated cellular signaling proteins have
the potential to provide efficient virus replication and cell transformation. Since there are powerful
inhibitors known for CK2 kinase activity, CK2 might become an attractive target for the inhibition of
EBV replication and cell transformation
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. Furthermore, both inhibitors increased
the message for insulin and boosted the secretion of insulin from storage vesicles. Thus, regarding
the high specificity of SGC-CK2-1, we can clearly attribute the observed effects to biological functions
of protein kinase CK2
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. To study the interaction between PDX-1 and PCIF1 we used immunofluorescence analysis, co-immunoprecipitation, GST-pull-down studies, and proximity ligation assay (PLA). For the analysis of the stability of PDX-1 we performed a cycloheximide chase. We used PDX-1 in its wild-type form as well as phosphomutants of the CK2 phosphorylation site. In pancreatic β-cells PDX-1 binds to PCIF1. The phosphorylation of PDX-1 by CK2 increases the ratio of PCIF1 bound to PDX-1. The stability of PDX-1 is extended in the absence of CK2 phosphorylation. Our results identified protein kinase CK2 as new important modulator of the stability of PDX-1
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 Ca2+-permeable TRPM3 channels that contribute to the elevation of the intracellular Ca2+ concen tration and the fusion of insulin granules with the plasma membrane. Conversely, glucose-induced
Ca2+ signals and insulin release are reduced by the activity of the serine/threonine kinase CK2. There fore, we hypothesized that TRPM3 channels might be regulated by CK2 phosphorylation. We used
recombinant TRPM3α2 proteins, native TRPM3 proteins from INS-1 β-cells, and TRPM3-derived
oligopeptides to analyze and localize CK2-dependent phosphorylation of TRPM3 channels. The func tional consequences of CK2 phosphorylation upon TRPM3-mediated Ca2+ entry were investigated
in Fura-2 Ca2+-imaging experiments. Recombinant TRPM3α2 channels expressed in HEK293 cells
displayed enhanced Ca2+ entry in the presence of the CK2 inhibitor CX-4945 and their activity was
strongly reduced after CK2 overexpression. TRPM3α2 channels were phosphorylated by CK2 in vitro
at serine residue 1172. Accordingly, a TRPM3α2 S1172A mutant displayed enhanced Ca2+ entry. The
TRPM3-mediated Ca2+ entry in INS-1 β-cells was also strongly increased in the presence of CX-4945
and reduced after overexpression of CK2. Our study shows that CK2-mediated phosphorylation
controls TRPM3 channel activity in INS-1 β-cells
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. In the past, a growing number of studies have reported on the important role of the protein kinase CK2 in the regulation of the survival and endocrine function of pancreatic β-cells. In fact, inhibition of CK2 is capable of reducing cytokine-induced loss of β-cells and increases insulin expression as well as secretion by various pathways that are regulated by reversible phosphorylation of proteins. Moreover, CK2 inhibition modulates pathways that are involved in the development of diabetes and prevents signal transduction, leading to late complications such as diabetic retinopathy. Hence, targeting CK2 may represent a novel therapeutic strategy for the treatment of diabetes
Protein Kinase CK2 Controls CaV2.1-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. This enhancement is preceded by a rise in the cytosolic Ca2+ concentration. Here, we identified the serine residues S2362 and S2364 of the voltage-dependent calcium channel CaV2.1 as targets of CK2 phosphorylation. Furthermore, co-immunoprecipitation experiments revealed that CaV2.1 binds to CK2 in vitro and in vivo. CaV2.1 knockdown experiments showed that the increase in the intracellular Ca2+ concentration, followed by an enhanced insulin secretion upon CK2 inhibition, is due to a Ca2+ influx through CaV2.1 channels. In summary, our results point to a modulating role of CK2 in the CaV2.1-mediated exocytosis of insulin
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. In order to shed more
light on the CK2-regulated network of glucose homeostasis, in the present study, a qRT-PCR array was
carried out with 84 diabetes-associated genes. After inhibition of CK2, fructose-1,6-bisphosphatase 1
(FBP1) showed a significant lower gene expression. Moreover, FBP1 activity was down-regulated.
Being a central enzyme of gluconeogenesis, the secretion of glucose was decreased as well. Thus,
FBP1 is a new factor in the CK2-regulated network implicated in carbohydrate metabolism control
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Automated and rapid identification of multidrug resistant Escherichia coli against the lead drugs of acylureidopenicillins, cephalosporins, and fluoroquinolones using specific Raman marker bands
A Raman-based, strain-independent, semi-automated method is presented that allows the rapid (<3 hours) determination of antibiotic susceptibility of bacterial pathogens isolated from clinical samples. Applying a priori knowledge about the mode of action of the respective antibiotic, we identified characteristic Raman marker bands in the spectrum and calculated batch-wise weighted sum scores from standardized Raman intensity differences between spectra of antibiotic exposed and nonexposed samples of the same strains. The lead substances for three relevant antibiotic classes (fluoroquinolone ciprofloxacin, third-generation cephalosporin cefotaxime, ureidopenicillin piperacillin) against multidrug-resistant Gram-negative bacteria (MRGN) revealed a high sensitivity and specificity for the susceptibility testing of two Escherichia coli laboratory strains and 12 clinical isolates. The method benefits from the parallel incubation of control and treated samples, which reduces the variance due to alterations in cultivation conditions and the standardization of differences between batches leading to long-term comparability of Raman measurements. © 2020 The Authors. Journal of Biophotonics published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei
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