A5002600082- Receptor Mechanisms and Signaling
- Protein Kinase Regulation and GTPase Signaling
- Melanoma and MAPK Pathways
- Neuropeptides and Animal Physiology
- Neuroscience and Neuropharmacology Research
- Signaling Pathways in Disease
- Cytokine Signaling Pathways and Interactions
- Cancer Mechanisms and Therapy
- Cellular Mechanics and Interactions
- Cellular transport and secretion
- Ubiquitin and proteasome pathways
- T-cell and B-cell Immunology
- Cell Adhesion Molecules Research
- PI3K/AKT/mTOR signaling in cancer
- NF-κB Signaling Pathways
- Cannabis and Cannabinoid Research
- Axon Guidance and Neuronal Signaling
- Ion channel regulation and function
- Neurological diseases and metabolism
- Neurotransmitter Receptor Influence on Behavior
- Immunotherapy and Immune Responses
- Endoplasmic Reticulum Stress and Disease
- Liver physiology and pathology
- Nerve injury and regeneration
- Computational Drug Discovery Methods
Institut Cochin
2010-2023
Université Paris Cité
2010-2023
Inserm
2009-2023
Centre National de la Recherche Scientifique
2011-2023
Délégation Paris 5
2010-2019
Sorbonne Paris Cité
2013-2019
Max Perutz Labs
2010
University of Vienna
2010
Sorbonne Université
2003-2009
Institut du Fer à Moulin
2003-2009
The cAMP response element-binding protein (CREB) has been shown to mediate transcriptional activation of genes in both and calcium influx signal transduction pathways. roles two multifunctional calcium/calmodulin-dependent kinases, CaMKIV CaMKII, were examined transient transfection studies that utilized either the full-length or constitutively active forms these kinases. results indicate is much more potent than CaMKII activating CREB three different cell lines. It was also found Ser133...
Many drugs of abuse exert their addictive effects by increasing extracellular dopamine in the nucleus accumbens, where they likely alter plasticity corticostriatal glutamatergic transmission. This mechanism implies key molecular alterations neurons which both and glutamate inputs are activated. Extracellular signal-regulated kinase (ERK), an enzyme important for long-term synaptic plasticity, is a good candidate playing such role. Here, we show mouse that d -amphetamine activates ERK subset...
The cellular response to treatment with proinflammatory cytokines or exposure environmental stress is mediated, in part, by the p38 group of mitogen-activated protein (MAP) kinases. We report molecular cloning a novel isoform MAP kinase, p38β2. This like p38α, inhibited pyridinyl imidazole drug SB203580. kinase MKK6 identified as common activator p38β2, and p38γ isoforms, while MKK3 activates only p38α isoforms. signal transduction pathways are therefore coupled distinct, but overlapping,...
We have characterized Ca2+/calmodulin-dependent protein kinase IV (CaM IV), expressed using the baculovirus/Sf9 cell system, to assess its potential role in Ca2+-dependent transcriptional regulation. CaM was strongly inhibited vitro by KN-62, a specific inhibitor which suppresses transcription of several genes, so we tested whether could stimulate transcription. Co-transfection COS-1 cells cDNA for gave 3-fold stimulation reporter gene expression, whereas co-transfection with II no...
Endocannabinoids form a novel class of intercellular messengers, the functions which include retrograde signaling in brain and mediation or modulation several types synaptic plasticity. Yet, mechanisms long-term effects stimulation CB1 cannabinoid receptors (CB1-R) are poorly understood. We show that anandamide, 2-arachidonoyl-glycerol, Δ9-tetrahydrocannabinol (THC) activated extracellular signal-regulated kinase (ERK) hippocampal slices. In living mice, THC ERK neurons induced its...
Membrane depolarization of NG108 cells gives rapid (< 5 min) activation Ca2+/calmodulin-dependent protein kinase IV (CaM-KIV), as well c-Jun N-terminal (JNK). To investigate whether the Ca2+-dependent mitogen-activated kinases (ERK, JNK, and p38) might be mediated by CaM cascade, we have transfected PC12 cells, which lack CaM-KIV, with constitutively active mutants and/or CaM-KIV (CaM-KKc CaM-KIVc, respectively). In absence depolarization, CaM-KKc transfection had no effect on...
Recent studies have demonstrated that Ca2+/calmodulin-dependent protein kinase IV (CaM-kinase IV) can mediate Ca2+-dependent regulation of gene expression through the phosphorylation transcriptional activating proteins. We previously identified and purified a 68-kDa rat brain CaM-kinase phosphorylates increases total Ca2+-independent activities (Tokumitsu, H., Brickey, D. A., Gold, J., Hidaka, Sikela, Soderling, T. R.(1994) J. Biol. Chem. 269, 28640-28647). Using partial amino acid sequence...
β-arrestins (βarrs) are two highly homologous proteins that uncouple G protein-coupled receptors from their cognate proteins, serve as adaptor molecules linking to clathrin-coat components (AP-2 complex and clathrin), act scaffolding for ERK1/2 JNK3 cascades. A striking difference between the βarrs (βarr1 βarr2) is βarr1 evenly distributed throughout cell, whereas βarr2 shows an apparent cytoplasmic localization at steady state. Here, we investigate molecular determinants underlying this...
Accumulating evidence suggests that the insect and mammalian innate immune response is mediated by homologous regulatory components.Proinflammatory cytokines bacterial lipopolysaccharide stimulate immunity activating transcription factors such as NF-B AP-1.One of responses evoked these stimuli initiation a kinase cascade leads to phosphorylation p38 mitogen-activated protein (MAP) on Thr Tyr within motif Thr-Gly-Tyr, which located subdomain VIII.We have investigated possible involvement MAP...
The chemotropic guidance cue netrin-1 promotes neurite outgrowth through its receptor Deleted in Colorectal Cancer (DCC) via activation of Rac1. guanine nucleotide exchange factor (GEF) linking netrin-1/DCC to Rac1 has not yet been identified. Here, we show that the RhoGEF Trio mediates signaling. We found interacts with DCC mouse embryonic brains and netrin-1-induced brain is impaired absence Trio. Trio−/− cortical neurons fail extend neurites response netrin-1, while they are able respond...
Nuclear factor of activated T cells (NFAT) is implicated in multiple biological processes, including cytokine gene expression, cardiac hypertrophy, and adipocyte differentiation.A conserved NFAT homology domain identified all members.Dephosphorylation the region critical for nuclear translocation transcriptional activation.Here we demonstrate that NFATc4 phosphorylated by p38 mitogen-activated protein (MAP) kinase but not JNK.The MAP phosphorylates residues, Ser 168 170 , NFATc4.Replacement...
Recent studies indicate multiple mechanisms are involved in Ca2+ stimulation of gene expression.We have used cell-permeable, specific inhibitors calmodulindependent protein kinases (CaM kinases) and phosphatase (calcineurin) to investigate the involvement these enzymes transcriptional regulation three immediate early genes PC12 cells stimulated with &18, or KCl.Preincubation CaM kinase inhibitor KN-62 blocked autophosphorylation I1 response by ionophore pt.sl,,.KN-62 treatment also resulted...
c-Jun N-terminal kinases (JNKs) (comprising JNK1–3 isoforms) are members of the MAPK (mitogen-activated protein kinase) family, activated in response to various stimuli including growth factors and inflammatory cytokines. Their activation is facilitated by scaffold proteins, notably JNK-interacting protein-1 (JIP1). Originally considered be mediators neuronal degeneration stress injury, recent studies support a role JNKs early stages neurite outgrowth, adult axonal regeneration. However,...
CD4 ؉ and CD8 T cells play specific roles during an immune response.Different molecular mechanisms could regulate the proliferation, death, effector functions of these two subsets cells.The p38 mitogen-activated protein (MAP) kinase pathway is induced by cytokines environmental stress has been associated with cell death cytokine expression.Here we report that activation MAP in vivo causes a selective loss due to induction apoptosis.In contrast, does not induce T-cell death.The apoptosis...
The development of T cells in the thymus is coordinated by cell-specific gene expression programs that involve multiple transcription factors and signaling pathways. Here, we show p38 mitogen-activated protein (MAP) kinase pathway strictly regulated during differentiation CD4−CD8− thymocytes. Persistent activation MAP blocks fetal thymocyte at CD25+CD44− stage vivo, results lack peripheral immune system adult mice. Inactivation required for further these into CD4+CD8+ arrest cell cycle...
Abstract Background Focal adhesion kinase (FAK) is a non-receptor tyrosine critical for processes ranging from embryo development to cancer progression. Although isoforms with specific molecular and functional properties have been characterized in rodents chicken, the organization of FAK gene throughout phylogeny its potential generate multiple are not well understood. Here, we study FAK, gene, post-transcriptional processing human. Results A single orthologue related PYK2 was found...
The conversion of prion protein (PrPC) to its protease-resistant isoform is involved in the pathogenesis diseases. Although PrPC highly expressed neurons and other cell types, physiological function still remains elusive. Here, we describe how evaluated expression, subcellular localization putative brain endothelial cells, which constitute blood-brain barrier. We detected expression microvascular endothelium mouse sections at intercellular junctions freshly isolated microvessels cultured...