Search results for "Phosphorylation"
showing 10 items of 975 documents
Phosphorylation of Elp1 by Hrr25 is required for elongator-dependent tRNA modification in yeast.
2014
Elongator is a conserved protein complex comprising six different polypeptides that has been ascribed a wide range of functions, but which is now known to be required for modification of uridine residues in the wobble position of a subset of tRNAs in yeast, plants, worms and mammals. In previous work, we showed that Elongator's largest subunit (Elp1; also known as Iki3) was phosphorylated and implicated the yeast casein kinase I Hrr25 in Elongator function. Here we report identification of nine in vivo phosphorylation sites within Elp1 and show that four of these, clustered close to the Elp1 C-terminus and adjacent to a region that binds tRNA, are important for Elongator's tRNA modification…
SIK2 orchestrates actin-dependent host response upon Salmonella infection
2021
Significance Through conducting quantitative proteomics upon Salmonella infection, we identified a SIK2 signaling network, implementing the kinase into a so far concealed biological function. Our data exposed SIK2 as a central orchestrator of an actin regulatory network, coordinating the stability of Salmonella-containing vacuole (SCV) and cellular actin assembly, in order to limit the acute phase of the infection. Most strikingly, SIK2 is not exclusively acting locally on actin assembly associated with the SCV but impacts the actin cytoskeleton architecture in its entirety upon Salmonella infection. Our work provides a mechanistic framework for how the actin cytoskeleton is regulated and h…
Mitochondrial proteomics profile points oxidative phosphorylation as main target for beauvericin and enniatin B mixture
2020
Abstract Beauvericin (BEA) and enniatin B (EN B) are non-legislated Fusarium mycotoxins usually found in cereal and cereal-based products all around the world. By the proteomic analysis of mitochondria enriched extracts from Jurkat cells exposed for 24 h to three concentrations of BEA:EN B (0.01–0.1–0.5 μM), a number of 1821 proteins (202 mitochondrial) were identified and relatively quantified. 340 proteins (59 mitochondrial) were statistically significant altered in our samples (Anova p-value ≤ 0.05 and fold change (FC) ≥1.5). The protein mitochondrial translational release factor 1 like (MTRF1L) was the most abundant protein in the three mycotoxin exposures studied. The mycotoxins mixtur…
Multi-laboratory experiment PME11 for the standardization of phosphoproteome analysis
2022
6 p.-2 fig.-2 tab.
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…
Piclamilast inhibits the pro-apoptotic and anti-proliferative responses of A549 cells exposed to H(2)O(2) via mechanisms involving AP-1 activation.
2012
Reactive oxygen species (ROS) are involved in the pathogenesis of many inflammatory diseases such as chronic obstructive pulmonary disease (COPD). They can alter the expression of genes involved in cellular damage by activating transcription factors, including the NF-κB and the activator protein 1 (AP-1). Phosphodiesterase type 4 (PDE4) inhibitors have anti-inflammatory and antioxidant effects, as described in in vivo and in vitro COPD models. This study analysed the effects of piclamilast, a selective PDE4 inhibitor, on modulating the global gene expression profile in A549 cells exposed to H(2)O(2).Changes in gene expression were analysed using high-density Affymetrix microarrays and valid…
Mitochondrial complex I: new insights from inhibitor assays
2000
The NADH:ubiquinone oxidoreductase (complex I) of the mitochondrial respiratory chain is by far the most complicated of the proton-translocating enzymes involved in the oxidative phosphorylation. Many clues regarding both electron transfer and proton translocation are still unknown. In this sense, inhibitor assays are relevant and useful pieces for elaborating a suitable model to explain the elusive bioenergetic mechanism of this enzyme. This short review presents the most recent advances in inhibitor studies and highlights the major controversies.
Oxidative Stress and Respiratory System: Pharmacological and Clinical Reappraisal of N-Acetylcysteine
2014
Abstract The large surface area for gas exchange makes the respiratory system particularly susceptible to oxidative stress-mediated injury. Both endogenous and exogenous pro-oxidants (e.g. cigarette smoke) trigger activation of leukocytes and host defenses. These mechanisms interact in a ìmultilevel cycleî responsible for the control of the oxidant/antioxidant homeostasis. Several studies have demonstrated the presence of increased oxidative stress and decreased antioxidants (e.g. reduced glutathione [GSH]) in subjects with chronic obstructive pulmonary disease (COPD), but the contribution of oxidative stress to the pathophysiology of COPD is generally only minimally discussed. The aim of t…
Regulation of endothelial nitric oxide synthase (eNOS) in myocardium subjected to cardioplegic arrest.
2009
BACKGROUND: Nitric oxide (NO) production by both coronary endothelial cells and cardiomyocytes is thought to play a significant role in myocardial pathophysiology following ischemia/reperfusion (I/R). METHODS: In thirteen pigs subjected to 1 hour cardioplegic arrest (CA) on CPB, left ventricular (LV) biopsies were collected prior to CPB (baseline), at 60 min CPA, at 15 and 30 min reperfusion on CPB, and at 120 min post CPB. LV specimens were immunocytochemically stained against phospho-eNOS Ser1177 , phospho-eNOS Thr495 , phosphorylated ERK1/2, and AKT/PKB. Four additional pigs without CA served as controls. Cardiomyocytes were quantitatively investigated using TV densitometry (gray units: …
Aclidinium inhibits human lung fibroblast to myofibroblast transition
2011
Background Fibroblast to myofibroblast transition is believed to contribute to airway remodelling in lung diseases such as asthma and chronic obstructive pulmonary disease. This study examines the role of aclidinium, a new long-acting muscarinic antagonist, on human fibroblast to myofibroblast transition. Methods Human bronchial fibroblasts were stimulated with carbachol (10 −8 to 10 −5 M) or transforming growth factor-β1 (TGF-β1; 2 ng/ml) in the presence or absence of aclidinium (10 −9 to 10 −7 M) or different drug modulators for 48 h. Characterisation of myofibroblasts was performed by analysis of collagen type I and α-smooth muscle actin (α-SMA) mRNA and protein expression as well as α…