Search results for "PROTEIN KINASE"
showing 10 items of 1188 documents
Role of cAMP in mediating AHR signaling.
2009
Regulation of the nuclear import of many transcription factors represents a step in gene regulation which is crucial for a number of cellular processes. The aryl hydrocarbon receptor (AHR), a basic helix-loop-helix protein of the PAS (PER-ARNT-SIM) family of transcriptional regulators is a cytosol-associated and ligand-activated receptor. The environmental toxin dioxin binds with high affinity to AHR rendering it nuclear and leading to the activation of AHR sensitive genes. However, the fact, that the AHR mediates a large variety of physiological events without the involvement of any known exogenous ligand, including liver and vascular system development, maturation of the immune system, re…
Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity.
2008
Colon carcinoma is one of the leading causes of death from cancer and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, it was reported that a population of undifferentiated cells from a primary tumor, so-called cancer stem cells (CSC), can reconstitute the original tumor on xenotransplantation. Here, we show that spheroid cultures of these colon CSCs contain expression of CD133, CD166, CD44, CD29, CD24, Lgr5, and nuclear β-catenin, which have all been suggested to mark the (cancer) stem cell population. More importantly, by using these spheroid cultures or freshly isolated tumor cells from multiple colon carcinomas, we now provide compelling…
NF-κB inducing kinase (NIK) is an essential post-transcriptional regulator of T-cell activation affecting F-actin dynamics and TCR signaling
2018
NF-κB inducing kinase (NIK) is the key protein of the non-canonical NF-κB pathway and is important for the development of lymph nodes and other secondary immune organs. We elucidated the specific role of NIK in T cells using T-cell specific NIK-deficient (NIKΔT) mice. Despite showing normal development of lymphoid organs, NIKΔT mice were resistant to induction of CNS autoimmunity. T cells from NIKΔT mice were deficient in late priming, failed to up-regulate T-bet and to transmigrate into the CNS. Proteomic analysis of activated NIK-/- T cells showed de-regulated expression of proteins involved in the formation of the immunological synapse: in particular, proteins involved in cytoskeleton dy…
Central Modulatory Neurons Control Fuel Selection in Flight Muscle of Migratory Locust
2003
Insect flight is one of the most intense and energy-demanding physiological activities. High carbohydrate oxidation rates are necessary for take-off, but, to spare the limited carbohydrate reserves, long-distance flyers, such as locusts, soon switch to lipid as the main fuel. We demonstrate that before a flight, locust muscles are metabolically poised for take-off by the release of octopamine from central modulatory dorsal unpaired median (DUM) neurons, which increases the levels of the potent glycolytic activator fructose 2,6-bisphosphate in flight muscle. Because DUM neurons innervating the flight muscles are active during rest but selectively inhibited during flight, they stimulate carbo…
Mechanisms of ceramide-induced COX-2-dependent apoptosis in human ovarian cancer OVCAR-3 cells partially overlapped with resveratrol.
2013
Ceramide is a member of the sphingolipid family of bioactive molecules demonstrated to have profound, diverse biological activities. Ceramide is a potential chemotherapeutic agent via the induction of apoptosis. Exposure to ceramide activates extracellular-signal-regulated kinases (ERK)1/2- and p38 kinase-dependent apoptosis in human ovarian cancer OVCAR-3 cells, concomitant with an increase in the expression of COX-2 and p53 phosphorylation. Blockade of cyclooxygenase-2 (COX-2) activity by siRNA or NS398 correspondingly inhibited ceramide-induced p53 Ser-15 phosphorylation and apoptosis; thus COX-2 appears at the apex of the p38 kinase-mediated signaling cascade induced by ceramide. Induct…
Anandamide-induced apoptosis in Chang liver cells involves ceramide and JNK/AP-1 pathway
2006
In the present study we demonstrate that anandamide, the most important endogenous cannabinoid, markedly induced apoptosis in Chang liver cells, an immortalized non-tumor cell line derived from normal liver tissue, while it induced only modest effects in a number of hepatoma cell lines. The apoptotic effect was reduced by methyl-beta-cyclodextrin, a membrane cholesterol depletor, suggesting an interaction between anandamide and the membrane microdomains named lipid rafts. Anandamide effects were mediated by the production of ceramide, as demonstrated by experiments performed with the sphingomyelinase inhibitor, desipramine, or with the sphingomyelinase activator, melittin. This conclusion w…
Control of the mutagenicity of aromatic amines by protein kinases and phosphatases
1997
The role of protein kinase C and protein phosphatases was examined in the control of mutagenic metabolites of aromatic amines. Various metabolic activating systems derived from rat liver were treated with: 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C modulator; okadaic acid (OA), a potent inhibitor of serine/threonine protein phosphatases (PP1 and PP2A); and ortho-vanadate (OV), an inhibitor of tyrosine phosphatases. TPA used over a wide concentration range (10−9–10−6 M) did not affect the bacterial mutagenicity of the aromatic amines and of the aromatic amide investigated, 2-aminoanthracene, 2-aminofluorene and 2-acetylaminofluorene (2AAF). At the molecular level, TPA did…
Ras-related GTPase Rhob represses NF-kappaB signaling.
2000
rhoB encoding a Ras-related GTPase is immediate-early inducible by genotoxic treatments, indicating that it is part of the cellular stress response. Here, we investigated the influence of RhoB on signal pathways that are rapidly evoked by genotoxic compounds. The data obtained show that wild-type RhoB neither affects activation of mitogen-activated protein kinases nor AP-1-dependent gene expression. However, RhoB inhibited both basal and genotoxic agent-stimulated activity of the transcription factor nuclear factor kappaB (NF-kappaB). Thus, RhoB attenuated alkylation-induced increase in the DNA binding activity of NF-kappaB and abrogated NF-kappaB-driven gene expression. Furthermore, RhoB i…
ChemInform Abstract: Synthesis of Pyrrolidin-2-ones and of Staurosporine Aglycon (K-252c) by Intermolecular Michael Reaction.
2010
Indolo[2,3-a]pyrrolo[3,4-c]carbazoles were isolated from nature, e.g., from low plants, especially fungi, as structurally rare natural substances. Responsible for naming and also the most important representative of this type is staurosporine (1), isolated from Streptomyces staurosporeus, and its aglycon (2), also known as staurosporinone or K-252c. 3,4-Disubstituted pyrrolidin-2-ones, a group of compounds with many interesting biological properties are related to staurosporinone. The most important property is the inhibition of protein kinase C (PKC), so that this antiproliferative agent can interfere with the cell cycle. The synthetic strategy, developed by us, allows the synthesis of pyr…
Light-Dependent Translocation of Arrestin in Rod Photoreceptors is Signaled through a Phospholipase C Cascade and Requires ATP
2009
Light adaptation of rod photoreceptors induces translocation of arrestin from inner segments (IS) to outer segments (OS). Our study suggests that components of the G-protein linked phosphoinositide pathway play a role in signaling the initiating events of arrestin translocation. We show that arrestin translocation can be stimulated by activators of phospholipase C (PLC) and protein kinase C (PKC) in the absence of light. Conversely, arrestin translocation to the OS is significantly slowed by inhibitors of PLC and PKC.In the second part of this study, we investigated the mechanism by which arrestin translocates in response to light. Other investigators have suggested that arrestin translocat…