Search results for "PROTEIN KINASES"
showing 10 items of 427 documents
Differential Roles of JNK in ConA/GalN and ConA-Induced Liver Injury in Mice
2008
Tumor necrosis factor-alpha-mediated liver injury can be induced by several different means; however, the signaling events and mechanisms of cell death are likely different. We investigated the mechanism of both apoptotic and necrotic hepatocyte cell death as well as the role of c-Jun NH2-terminal kinase (JNK) in the ConA and ConA/D-galactosamine (GalN) models of murine liver injury. ConA alone induced primarily necrotic cell death with no caspase activation, whereas ConA/GalN induced apoptosis in addition to necrotic cell death. The bi-modal death pattern in the ConA/GalN model was confirmed by the use of transgenic mice expressing a dominant-negative form of Fas-associated death domain in…
Calcium in plant defence‐signalling pathways
2006
In plant cells, the calcium ion is a ubiquitous intracellular second messenger involved in numerous signalling pathways. Variations in the cytosolic concentration of Ca2+ ([Ca2+]cyt) couple a large array of signals and responses. Here we concentrate on calcium signalling in plant defence responses, particularly on the generation of the calcium signal and downstream calcium-dependent events participating in the establishment of defence responses with special reference to calcium-binding proteins.
Kel1 is a phosphorylation-regulated noise suppressor of the pheromone signaling pathway.
2021
Abstract Mechanisms have evolved that allow cells to detect signals and generate an appropriate response. The accuracy of these responses relies on the ability of cells to discriminate between signal and noise. How cells filter noise in signaling pathways is not well understood. We have analyzed noise suppression in the yeast pheromone signaling pathway. By combining synthetic genetic array screening, mass spectrometry and single-cell time-resolved microscopy, we discovered that the poorly characterized protein Kel1 serves as a major noise suppressor of the pathway. At the molecular level, Kel1 suppresses spontaneous activation of the pheromone response by inhibiting membrane recruitment of…
Calcitonin gene-related peptide partly protects cultured smooth muscle cells from apoptosis induced by an oxidative stress via activation of ERK1/2 M…
2003
Abstract Oxidative stress induced by a glucose/glucose oxidase (G/GO) generator system dose-dependently decreased the viability of cultured vascular smooth muscle cells (VSMC) as estimated by MTT assay. Cell death was induced in 40% of cells exposed to 0.2 IU/ml of the free radical generating mixture. Annexin-V labeling, Hoechst staining together with DNA laddering demonstrated that apoptosis was responsible for this cell loss. Pretreatment of the cells with 10−8 M calcitonin gene-related peptide (CGRP) significantly attenuated the damaging effect of the oxidative stress. Indeed, cell viability was estimated to be 80% in CGRP-treated group, instead of 60% in absence of CGRP treatment. This …
Fatty acids liberated from low-density lipoprotein trigger endothelial apoptosis via mitogen-activated protein kinases.
2005
Enzymatic modification of low-density lipoprotein (LDL) as it probably occurs in the arterial intima drastically increases its cytotoxicity, which could be relevant for the progression of atherosclerotic lesions. LDL was treated with a protease and cholesterylesterase to generate a derivative similar to lesional LDL, with a high content of free cholesterol and fatty acids. Exposure of endothelial cells to the enzymatically modified lipoprotein (E-LDL), but not to native or oxidized LDL, resulted in programmed cell death. Apoptosis was triggered by apoptosis signal-regulating kinase 1 dependent phosphorylation of p38. Depletion and reconstitution experiments identified free fatty acids (FFA)…
Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP-1
2001
Glucocorticoids inhibit the proinflammatory activities of transcription factors such as AP-1 and NF-kappa B as well as that of diverse cellular signaling molecules. One of these signaling molecules is the extracellular signal-regulated kinase (Erk-1/2) that controls the release of allergic mediators and the induction of proinflammatory cytokine gene expression in mast cells. The mechanism of inhibition of Erk-1/2 activity by glucocorticoids is unknown. Here we report a novel dual action of glucocorticoids for this inhibition. Glucocorticoids increase the expression of the MAP kinase phosphatase-1 (MKP-1) gene at the promoter level, and attenuate proteasomal degradation of MKP-1, which we re…
Fumarate dependent protein composition under aerobic and anaerobic growth conditions in Escherichia coli
2020
Abstract In the absence of sugars, C4-dicarboxylates (C4DC) like fumarate represent important substrates for growth of Escherichia coli. Aerobically, C4DCs are oxidized to CO2 whereas anaerobically, C4DCs are used for fumarate respiration. In order to determine the impact of fumarate under aerobic and anaerobic conditions, proteomes of E. coli W3110 grown aerobically or anaerobically with fumarate and/or the non-C4DC substrate glycerol were comparatively profiled by nanoLC-MS/MS. Membrane enrichment allowed sensitive detection of membrane proteins. A total of 1657 proteins of which 646 and 374 were assigned to the cytosol or membrane, respectively, were covered. Presence of fumarate trigger…
Integrative genomic and proteomic analyses identify targets for Lkb1 deficient metastatic lung tumors
2010
SummaryIn mice, Lkb1 deletion and activation of KrasG12D results in lung tumors with a high penetrance of lymph node and distant metastases. We analyzed these primary and metastatic de novo lung cancers with integrated genomic and proteomic profiles, and have identified gene and phosphoprotein signatures associated with Lkb1 loss and progression to invasive and metastatic lung tumors. These studies revealed that SRC is activated in Lkb1-deficient primary and metastatic lung tumors, and that the combined inhibition of SRC, PI3K, and MEK1/2 resulted in synergistic tumor regression. These studies demonstrate that integrated genomic and proteomic analyses can be used to identify signaling pathw…
B-Raf Acts via the ROCKII/LIMK/Cofilin Pathway To Maintain Actin Stress Fibers in Fibroblasts
2004
Members of the Raf family of serine/threonine protein kinases have been well studied in a variety of organisms ranging from Drosophila to humans. Three raf homologues (raf-1, B-raf, and A-raf) exist in mammals, while a single prototypic homologue exists in lower organisms. A wealth of genetic and biochemical data have indicated that Raf family members are signaling kinases that are integral components of the conserved Ras/Raf/MEK/ERK signaling cascade. Following activation by Ras-dependent mechanisms, Raf protein kinases act as mitogen-activated protein (MAP) kinase kinase kinases, which phosphorylate and activate the type 1/2 MAP kinase kinases, also known as MEK1/2. These dual-specificity…
Aclidinium inhibits cholinergic and tobacco smoke-induced MUC5AC in human airways.
2010
Mucus hypersecretion and mucin MUC5AC overexpression are pathological features of chronic obstructive pulmonary disease (COPD). This study examines the inhibitory effect of aclidinium, a new long-acting muscarinic antagonist, on MUC5AC expression in human airway epithelial cells. MUC5AC mRNA (RT-PCR) and protein expression (ELISA and immunohistochemistry) were studied in human bronchial tissue and differentiated human airway epithelial cells activated with carbachol (100 μM) or cigarette smoke extract in the absence or presence of aclidinium. Carbachol increased MUC5AC mRNA and protein expression in human bronchus and cultured epithelial cells. Aclidinium inhibited the carbachol-induced MUC…