A5045893326- NF-κB Signaling Pathways
- interferon and immune responses
- Peptidase Inhibition and Analysis
- Immune Response and Inflammation
- Magnesium in Health and Disease
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Immune cells in cancer
- Cellular Mechanics and Interactions
- Trace Elements in Health
- Plant Micronutrient Interactions and Effects
- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cancer Immunotherapy and Biomarkers
- Ubiquitin and proteasome pathways
- Immunotherapy and Immune Responses
- Asthma and respiratory diseases
- Fibroblast Growth Factor Research
- Biochemical and Molecular Research
- Ion Channels and Receptors
- Phagocytosis and Immune Regulation
- Cancer-related Molecular Pathways
- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Pancreatic and Hepatic Oncology Research
University of Pittsburgh
2023-2025
University at Buffalo, State University of New York
2023-2024
MRC Protein Phosphorylation and Ubiquitylation Unit
2008-2022
University of Dundee
2008-2022
Boston University
2020-2021
Boston Medical Center
2020-2021
General Department of Preventive Medicine
2019
Medical Research Council
2011-2018
Radboud University Nijmegen
2006-2016
Radboud Institute for Molecular Life Sciences
2016
TANK-binding kinase 1 (TBK1) and IkappaB epsilon (IKKepsilon) regulate the production of Type interferons during bacterial viral infection, but lack useful pharmacological inhibitors has hampered progress in identifying additional physiological roles these protein kinases how they are regulated. Here we demonstrate that BX795, a potent relatively specific inhibitor TBK1 IKKepsilon, blocked phosphorylation, nuclear translocation, transcriptional activity interferon regulatory factor 3 and,...
Members of the IKK {IκB [inhibitor NF-κB (nuclear factor κB)] kinase} family play a central role in innate immunity by inducing NF-κB- and IRF [IFN (interferon) regulatory factor]-dependent gene transcription programmes required for production pro-inflammatory cytokines IFNs. However, molecular mechanisms that activate these protein kinases their complement physiological substrates remain poorly defined. Using MRT67307, novel inhibitor IKKϵ/TBK1 (TANK {TRAF [TNF...
Macrophages acquire strikingly different properties that enable them to play key roles during the initiation, propagation, and resolution of inflammation. Classically activated (M1) macrophages produce proinflammatory mediators combat invading pathogens respond tissue damage in host, whereas regulatory (M2b) high levels anti-inflammatory molecules, such as IL-10, low cytokines, like IL-12, are important for inflammatory responses. A central problem this area is understand how formation can...
The polarization of macrophages into a regulatory-like phenotype and the production IL-10 plays an important role in resolution inflammation. We show this study that PGE2, combination with LPS, is able to promote anti-inflammatory characterized by high expression regulatory markers SPHK1 LIGHT via protein kinase A–dependent pathway. Both TLR agonists PGE2 phosphorylation transcription factor CREB on Ser133. However, although regulates transcription, mutation Ser133 Ala endogenous gene did...
Mutations in leucine-rich repeat kinase 2 (LRRK2) are strongly associated with late-onset autosomal dominant Parkinson's disease. LRRK2 is highly expressed immune cells and recent work points towards a link between innate immunity. Here we demonstrate that stimulation of the Toll-Like Receptor (TLR) pathway by MyD88-dependent agonists bone marrow-derived macrophages (BMDMs) or RAW264.7 induces marked phosphorylation at Ser910 Ser935, sites regulate binding 14-3-3 to LRRK2. Phosphorylation...
Toll-like receptor (TLR) ligands that signal via TIR-domain-containing adapter-inducing IFNβ (TRIF) activate the IκB kinase (IKK)-related kinases, TRAF associated NFκB activator (TANK)-binding kinase-1 (TBK1) and IKKε, which then phosphorylate IRF3 induce production of IFNβ. Here we show TBK1 IKKε are also activated by TLR MyD88. Notably, activation is rapid, transient, it precedes a more prolonged TBK1. The MyD88- TRIF-dependent signaling pathways IKK-related kinases two pathways. One...
IKKβ {IκB [inhibitor of NF-κB (nuclear factor κB)] kinase β} is required to activate the transcription NF-κB, but how itself activated in vivo still unclear. It was found require phosphorylation by one or more ‘upstream’ protein kinases some reports, autophosphorylation others. In present study, we resolve this contro-versy demonstrating that activation induced IL-1 (interleukin-1) TNF (tumour necrosis factor) embryonic fibroblasts, ligands Toll-like receptors macrophages, requires two...
TRPM7 is a ubiquitously expressed nonspecific cation channel that has been implicated in cellular Mg2+ homeostasis. We have recently shown moderate overexpression of neuroblastoma N1E-115 cells elevates cytosolic Ca2+ levels and enhances cell-matrix adhesion. Furthermore, activation by phospholipase C (PLC)-coupled receptor agonists caused further increase intracellular augmented cell adhesion spreading Ca2+-dependent manner (1Clark K. Langeslag M. van Leeuwen B. Ran L. Ryazanov A.G. Figdor...
TRPM6 and TRPM7 are bifunctional proteins expressing a TRP channel fused to an atypical α-kinase domain. While the gating properties of channels have been studied in detail, little is known about mechanisms regulating kinase activity. Recently, we found that associates with its substrate myosin II via kinase-dependent mechanism suggesting role for autophosphorylation recognition. Here, demonstrate cytosolic C-terminus undergoes massive (32±4 mol/mol), which strongly increases rate...
Macrophages switch to an anti-inflammatory, 'regulatory'-like phenotype characterized by the production of high levels interleukin (IL)-10 and low pro-inflammatory cytokines promote resolution inflammation. A potential therapeutic strategy for treatment chronic inflammatory diseases would be administer drugs that could induce formation macrophages at sites In present study, we demonstrate clinically approved cancer bosutinib dasatinib several hallmark features macrophages. Treatment with or...
The salt-inducible kinases (SIKs) control a novel molecular switch regulating macrophage polarization. Pharmacological inhibition of the SIKs induces phenotype characterized by secretion high levels anti-inflammatory cytokines, including interleukin (IL)-10, and very low pro-inflammatory such as tumour necrosis factor α. SIKs, therefore, represent attractive new drug targets for treatment macrophage-driven diseases, but which three isoforms, SIK1, SIK2 or SIK3, would be appropriate to target...
MINT‐6700314: GNA1 (uniprotkb:Q96EK6) and bind (MI:0407) by X-ray crystallography (MI:0114)
By conjugation of proteins to beads, Ags can be selectively targeted into the MHC class I pathway phagocytes in vivo and stimulate CTL responses. Because also present particulate Ag on II molecules, we examined whether these stimulated concomitant CD4 T cell immunity. Although priming cells with soluble OVA required adjuvants, was stimulatory when injected saline. We next responses played a role generation Ag. At low concentrations Ag, primed CTLs wild-type mice but not II-deficient animals,...
Abstract Eosinophil degranulation is thought to play a pivotal role in the pathogenesis of allergic disorders. Although mouse models disorders have been used extensively identify contribution eosinophils disease, ultrastructural evidence active granule disassembly has not reported. In this investigation, we characterized degree eosinophil activation bone marrow, blood, lung tissue, and airways lumen [bronchoalveolar lavage fluid (BALF)] ovalbumin-sensitized aero-challenged wild-type...