Search

Your search keyword '"MESH: Protein-Serine-Threonine Kinases/metabolism"' showing total 5 results
Start Over Descriptor "MESH: Protein-Serine-Threonine Kinases/metabolism"
5 results on '"MESH: Protein-Serine-Threonine Kinases/metabolism"'

1. Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia

Author

Tamas L. Horvath, Maria Teresa Dell’Anno, Xiao-Bing Gao, Naoki Nakagawa, Anze Testen, Yalan Zhang, Tianliuyun Gao, Mihovil Pletikos, Candace Bichsel, Nenad Sestan, Mingfeng Li, Sirisha Pochareddy, Brett D. Lindenbach, Leonard K. Kaczmarek, Zhen Li, Wenqi Han, Forrest O. Gulden, Fuchen Liu, André M. M. Sousa, Stephen M. Strittmatter, Andrew T.N. Tebbenkamp, Marco Onorati, Steven Lisgo, Jernej Mlakar, Marie Flamand, Mara Popović, Eva S. Anton, Luis Varela, Klara Szigeti-Buck, Ying Zhu, Department of Neuroscience [New Haven], Yale University School of Medicine-Kavli Institute for Neuroscience [New Haven], Department of Cell Biology and Physiology, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Cellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience [New Haven], Yale University School of Medicine, Section of Comparative Medicine [New Haven], Institute of Genetic Medicine, Newcastle University [Newcastle], Departments of pharmacology and molecular biophysics and biochemistry [New Haven], University of Ljubljana, Département de Virologie - Department of Virology, Institut Pasteur [Paris], Departments of Internal Medicine, Cellular & Molecular Physiology, Departments of Medicine and Cell Biology & Physiology, Department of Microbial Pathogenesis, Reproductive Neuroscience Unit, Department of Obstetrics and Gynecology and Department of Neurobiology, Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism, Kavli Institute for Neuroscience [New Haven], Departments of Psychiatry and Genetics, This work was supported by grants NS076503, MH103339, MH105972, MH106934, MH060929, NS080388, AG034924, AG047270, DC01919, AI120113, and AI089826 from the NIH, SFARI 307705 from the Simons Foundation, and 15-RMA-YALE-31 from Connecticut Innovations’ Regenerative Medicine Research Fund. The Laboratory of Developmental Biology at the University of Washington, Seattle, and Human Developmental Biology Resource were supported by NIH award number HD0008836 and the Joint MRC/Wellcome Trust grant 099175/Z/12/Z, respectively. Additional support was provided by the Kavli Foundation and the Falk Medical Research Trust., Department of Neuroscience, Yale University School of Medicine, Yale School of Medicine [New Haven, Connecticut] (YSM), Institut Pasteur [Paris] (IP), Kavli Institute for Neuroscience, Yale School of Medicine, and Yale School of Medicine [New Haven, Connecticut] (YSM)-Yale School of Medicine [New Haven, Connecticut] (YSM)

Subjects
Genetics and Molecular Biology (all), Microcephaly, Transcription, Genetic, Neocortex, MESH: Neuroepithelial Cells/ultrastructure, Biochemistry, environment and public health, MESH: Brain/virology, Neural Stem Cells, MESH: Centrosome/drug effects, MESH: Mitochondria/metabolism, lcsh:QH301-705.5, Neurons, MESH: Protein-Serine-Threonine Kinases/metabolism, Zika Virus Infection, Brain, MESH: Neurons/virology, MESH: Neural Stem Cells/virology, MESH: Neural Stem Cells/immunology, Nucleosides, MESH: Zika Virus/physiology, MESH: Virus Replication/drug effects, Neural stem cell, 3. Good health, Cell biology, Neuroepithelial cell, MESH: Brain/pathology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Spinal Cord, MESH: Neocortex/pathology, MESH: Neuroepithelial Cells/immunology, Neuroglia, MESH: Receptor Protein-Tyrosine Kinases/metabolism, Article, General Biochemistry, Genetics and Molecular Biology, MESH: Protein Kinase Inhibitors/pharmacology, 03 medical and health sciences, MESH: Gene Expression Profiling, Fetus, Humans, MESH: Phosphorylation/drug effects, Mitosis, MESH: Neural Stem Cells/ultrastructure, Biochemistry, Genetics and Molecular Biology (all), MESH: Humans, Receptor Protein-Tyrosine Kinases, MESH: Zika Virus/pathogenicity, medicine.disease, Immunity, Innate, MESH: Mitosis/drug effects, 030104 developmental biology, MESH: Neuroprotective Agents/pharmacology, MESH: Mitochondria/drug effects, MESH: Spinal Cord/pathology, MESH: Neuroglia/ultrastructure, 0301 basic medicine, MESH: Fetus/virology, viruses, [SDV]Life Sciences [q-bio], Neuroepithelial Cells, MESH: Zika Virus/ultrastructure, Virus Replication, MESH: Neurons/drug effects, MESH: Neuroepithelial Cells/drug effects, MESH: Zika Virus Infection/pathology, MESH: Neurons/pathology, MESH: Immunity, Innate/drug effects, Phosphorylation, Genetics, Cell Death, MESH: Transcription, Genetic/drug effects, MESH: Neuroglia/virology, MESH: Nucleosides/pharmacology, Mitochondria, Neuroprotective Agents, MESH: Neuroglia/pathology, lipids (amino acids, peptides, and proteins), MESH: Zika Virus Infection/virology, Stem cell, Programmed cell death, MESH: Centrosome/metabolism, MESH: Brain/embryology, Protein Serine-Threonine Kinases, Biology, Proto-Oncogene Proteins, MESH: Microcephaly/pathology, medicine, MESH: Zika Virus/drug effects, Protein Kinase Inhibitors, Centrosome, MESH: Neural Stem Cells/enzymology, Gene Expression Profiling, MESH: Proto-Oncogene Proteins/metabolism, Zika Virus, Axl Receptor Tyrosine Kinase, MESH: Microcephaly/virology, Gene expression profiling, MESH: Cell Death/drug effects, lcsh:Biology (General), MESH: Neuroepithelial Cells/virology
Abstract

SummaryThe mechanisms underlying Zika virus (ZIKV)-related microcephaly and other neurodevelopment defects remain poorly understood. Here, we describe the derivation and characterization, including single-cell RNA-seq, of neocortical and spinal cord neuroepithelial stem (NES) cells to model early human neurodevelopment and ZIKV-related neuropathogenesis. By analyzing human NES cells, organotypic fetal brain slices, and a ZIKV-infected micrencephalic brain, we show that ZIKV infects both neocortical and spinal NES cells as well as their fetal homolog, radial glial cells (RGCs), causing disrupted mitoses, supernumerary centrosomes, structural disorganization, and cell death. ZIKV infection of NES cells and RGCs causes centrosomal depletion and mitochondrial sequestration of phospho-TBK1 during mitosis. We also found that nucleoside analogs inhibit ZIKV replication in NES cells, protecting them from ZIKV-induced pTBK1 relocalization and cell death. We established a model system of human neural stem cells to reveal cellular and molecular mechanisms underlying neurodevelopmental defects associated with ZIKV infection and its potential treatment.

Published
2016

2. Strategies to interfere with PDZ-mediated interactions in neurons: What we can learn from the rabies virus

Author

Elouan Terrien, Nicolas Babault, Nicolas Wolff, Monique Lafon, Florence Cordier, Pierre Maisonneuve, Célia Caillet-Saguy, Florent Delhommel, Plateforme technologique de RMN biologique - Biological NMR Technological Platform, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Cellule Pasteur UPMC, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP), Neuro-Immunologie Virale, This work was supported by grants from the Institut Pasteur, Agence Nationale pour la Recherche and Institut Carnot Pasteur Maladies Infectieuses. N.B., E.T., P.M. and F.D. are recipients of fellowships from the Ministère de l’Enseignement Supérieur et de la Recherche and the Fondation pour la Recherche Médicale., Prof. Henri Buc is ackowledged for helpul discussion., Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris]

Subjects
Cell signaling, G protein, Viral protein, Enzymatic regulation, MESH: PDZ Domains, [SDV]Life Sciences [q-bio], PDZ domain, Molecular Sequence Data, Biophysics, Cellular homeostasis, PDZ Domains, MESH: Amino Acid Sequence, Biology, Protein Serine-Threonine Kinases, medicine.disease_cause, 03 medical and health sciences, MESH: Rabies virus/physiology, 0302 clinical medicine, MESH: Neurons/enzymology, medicine, MESH: Protein Binding, Animals, Humans, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Phosphorylation, Molecular Biology, Neuronal signaling, MESH: Neurons/cytology, 030304 developmental biology, MESH: Protein-Serine-Threonine Kinases/metabolism, Neurons, 0303 health sciences, MESH: Humans, MESH: Molecular Sequence Data, Kinase, Rabies virus, Protein Tyrosine Phosphatase, Non-Receptor Type 4, MESH: Neurons/metabolism, MESH: Neurons/virology, MESH: Protein Tyrosine Phosphatase, Non-Receptor Type 4/metabolism, Cell biology, MESH: Rabies virus/metabolism, 030217 neurology & neurosurgery, Protein Binding
Abstract

International audience; PDZ (PSD-95/Dlg/ZO-1) domains play a major role in neuronal homeostasis in which they act as scaffold domains regulating cellular trafficking, self-association and catalytic activity of essential proteins such as kinases and phosphatases. Because of their central role in cell signaling, cellular PDZ-containing proteins are preferential targets of viruses to hijack cellular function to their advantage. Here, we describe how the viral G protein of the rabies virus specifically targets the PDZ domain of neuronal enzymes during viral infection. By disrupting the complexes formed by cellular enzymes and their ligands, the virus triggers drastic effect on cell signaling and commitment of the cell to either survival (virulent strains) or death (vaccinal strains). We provide structural and biological evidences that the viral proteins act as competitors endowed with specificity and affinity in an essential cellular process by mimicking PDZ binding motif of cellular partners. Disruption of critical endogenous protein-protein interactions by viral protein drastically alters intracellular protein trafficking and catalytic activity of cellular proteins that control cell homeostasis. This work opens up many perspectives to mimic viral sequences and developing innovative therapies to manipulate cellular homeostasis.

Published
2014

3. Posttranscriptional Regulation of PER1 Underlies the Oncogenic Function of IRE

Author

Arisa Higa, Raphael Pineau, Michael Hallett, Stéphanie Lhomond, Olivier Pluquet, Marion Bouchecareilh, Anne Vital, Sandrine Loriot, Gaelle Cubel, Jann N. Sarkaria, Maylis Delugin, Hugues Loiseau, Wenting Wu, Nicolas Dejeans, Keith Anderson, Sara J. C. Gosline, Frédéric Saltel, Martin E. Fernandez-Zapico, Fausto J. Rodriguez, C. Combe, Jean Rosenbaum, Eric Chevet, Nathalie Dugot-Senant, Saïd Taouji, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), DIPI (DIPI), ENISE, Ecosystèmes aquatiques et changements globaux (UR EABX), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Centre de Recherche sur la Matière Divisée (CRMD), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Department of Health and Human Services, National Institutes of Health [Bethesda] (NIH), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), This work was supported by an Avenir program (INSERM), grants from the Institut National du Cancer (INCa), Ligue contre le cancer, a Marie Curie International Reintegration Grant (E. Chevet), a grant from the Mayo Clinic Cancer Centre (M.E. Fernandez-Zapico), a grant from Institut Fédératif de Recherche 66 (O. Pluquet). O. Pluquet was supported by fellowships from INSERM and Association pour la Recherche contre le Cancer. M. Bouchecareilh was supported from a fellowship from le Conseil Régional d'Aquitaine and la Fondation pour la Recherche Française (FRM). Human glioblastoma samples were collected through the Bordeaux Tumor Bank (JP Merlio, CHU Bordeaux, France) funded by the Cancéropôle Grand Sud-Ouest and by a CEREPEG project grant (PHRC 2003, H. Loiseau) or through the Mayo Clinic Department of Clinical Pathology and funded by the Mayo Clinic SPORE in Brain Cancer P50 CA108961 (Rochester)., The authors thank M. Moenner (Université Bordeaux 1, Bordeaux, France) for precious help and fruitful discussions, S. Manié (UMR CNRS 5286, INSERM 1052, Cancer Research Center of Lyon, Lyon, France), and the Chevet lab for critical reading of the manuscript. The authors also thank Dr S. Gery (University of California, Los Angeles, CA) for the gift of pcDNA3.1-hPER1 expression vector and Dr U. Albrecht (Freiburg, Switzerland) for providing us with the pPER1-Luc vector., Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), Diagnostics et imageries des procédés industriels (ENISE-DIPI), Ecole Nationale d'Ingénieurs de Saint Etienne (ENISE), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)

Subjects
Cancer Research, Endoribonuclease activity, [SDV]Life Sciences [q-bio], Circadian clock, MESH: Base Sequence, MESH: Period Circadian Proteins/metabolism, Mice, 0302 clinical medicine, RNA interference, MESH: Glioblastoma/metabolism, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Animals, RNA Processing, Post-Transcriptional, MESH: Gene Expression Regulation, Neoplastic/physiology, Oligonucleotide Array Sequence Analysis, Regulation of gene expression, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, Period Circadian Proteins, MESH: Protein-Serine-Threonine Kinases/genetics, Cell biology, Gene Expression Regulation, Neoplastic, Oncology, MESH: Endoribonucleases/metabolism, 030220 oncology & carcinogenesis, MESH: Glioblastoma/genetics, RNA Interference, PER1, MESH: RNA Processing, Post-Transcriptional, endocrine system, MESH: Xenograft Model Antitumor Assays, XBP1, Molecular Sequence Data, MESH: RNA Interference, MESH: Endoribonucleases/genetics, [SDV.CAN]Life Sciences [q-bio]/Cancer, Protein Serine-Threonine Kinases, Biology, Transfection, Article, 03 medical and health sciences, Endoribonucleases, MESH: Unfolded Protein Response/physiology, Animals, Humans, Gene silencing, MESH: Protein-Serine-Threonine Kinases/metabolism, RNA, Messenger, MESH: Mice, 030304 developmental biology, MESH: RNA, Messenger, MESH: Period Circadian Proteins/genetics, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, MESH: Transfection, Xenograft Model Antitumor Assays, Molecular biology, MESH: Oligonucleotide Array Sequence Analysis, Unfolded Protein Response, Unfolded protein response, Glioblastoma
Abstract

Growing evidence supports a role for the unfolded protein response (UPR) in carcinogenesis; however, the precise molecular mechanisms underlying this phenomenon remain elusive. Herein, we identified the circadian clock PER1 mRNA as a novel substrate of the endoribonuclease activity of the UPR sensor IRE1α. Analysis of the mechanism shows that IRE1α endoribonuclease activity decreased PER1 mRNA in tumor cells without affecting PER1 gene transcription. Inhibition of IRE1α signaling using either siRNA-mediated silencing or a dominant-negative strategy prevented PER1 mRNA decay, reduced tumorigenesis, and increased survival, features that were reversed upon PER1 silencing. Clinically, patients showing reduced survival have lower levels of PER1 mRNA expression and increased splicing of XBP1, a known IRE-α substrate, thereby pointing toward an increased IRE1α activity in these patients. Hence, we describe a novel mechanism connecting the UPR and circadian clock components in tumor cells, thereby highlighting the importance of this interplay in tumor development. Cancer Res; 73(15); 4732–43. ©2013 AACR.

Published
2013

4. Autocrine control of glioma cells adhesion and migration through IRE1α-mediated cleavage of SPARC mRNA

Author

Dejeans, N., Pluquet, O., Lhomond, S., Grise, F., Bouchecareilh, M., Juin, A., Meynard-Cadars, M., Bidaud-Meynard, A., Gentil, C., Moreau, V., Saltel, F., Chevet, E., Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine Purpan, This work was supported by the Avenir program of Institut National de la Santé et de la Recherche Médicale, Institut national du cancer, Ligue Contre le Cancer to E.C., the French Association pour la Recherche contre le Cancer to O.P., La Ligue contre le Cancer to N.D., and the Cancéropôle Grand Sud-Ouest to C.G., and We thank the Chevet lab for critical reading of the manuscript. We are indebted to Sebastien Marais (Bordeaux Imaging Center, Bordeaux, France) for help with the ImageJ program.

Subjects
cell migration, [SDV]Life Sciences [q-bio], MESH: Cell Movement*/genetics, MESH: Glioma/genetics, MESH: Brain Neoplasms/pathology, Cell Movement, MESH: Extracellular Matrix Proteins/metabolism, MESH: Actin Cytoskeleton/metabolism, Tumor Cells, Cultured, Osteonectin, MESH: Signal Transduction/genetics, MESH: Autocrine Communication*/genetics, Extracellular Matrix Proteins, Brain Neoplasms, MESH: Gene Expression Regulation, Neoplastic, Glioma, MESH: RNA, Messenger/metabolism, Gene Expression Regulation, Neoplastic, Actin Cytoskeleton, Autocrine Communication, MESH: Endoribonucleases/metabolism, MESH: Glioma/pathology, MESH: RNA, Messenger/genetics, Signal Transduction, Down-Regulation, [SDV.CAN]Life Sciences [q-bio]/Cancer, IRE1, Protein Serine-Threonine Kinases, MESH: Spheroids, Cellular/pathology, Models, Biological, MESH: Down-Regulation/genetics, MESH: Gene Expression Profiling, MESH: Cell Proliferation, Spheroids, Cellular, Endoribonucleases, Cell Adhesion, MESH: Osteonectin/genetics, MESH: Protein-Serine-Threonine Kinases/metabolism, Humans, MESH: Tumor Cells, Cultured, RNA, Messenger, MESH: Osteonectin/metabolism, MESH: rhoA GTP-Binding Protein/metabolism, Cell Proliferation, MESH: Extracellular Matrix Proteins/genetics, MESH: Humans, Gene Expression Profiling, MESH: Models, Biological, SPARC, MESH: Cell Adhesion/genetics, MESH: Brain Neoplasms/genetics, rhoA GTP-Binding Protein, Endoplasmic reticulum
Abstract

International audience; The endoplasmic reticulum (ER) is an organelle specialized for the folding and assembly of secretory and transmembrane proteins. ER homeostasis is often perturbed in tumor cells because of dramatic changes in the microenvironment of solid tumors, thereby leading to the activation of an adaptive mechanism named the unfolded protein response (UPR). The activation of the UPR sensor IRE1α has been described to play an important role in tumor progression. However, the molecular events associated with this phenotype remain poorly characterized. In the present study, we examined the effects of IRE1α signaling on the adaptation of glioma cells to their microenvironment. We show that the characteristics of U87 cell migration are modified under conditions where IRE1α activity is impaired (DN_IRE1). This is linked to increased stress fiber formation and enhanced RhoA activity. Gene expression profiling also revealed that loss of functional IRE1α signaling mostly resulted in the upregulation of genes encoding extracellular matrix proteins. Among these genes, Sparc, whose mRNA is a direct target of IRE1α endoribonuclease activity, was in part responsible for the phenotypic changes associated with IRE1α inactivation. Hence, our data demonstrate that IRE1α is a key regulator of SPARC expression in vitro in a glioma model. Our results also further support the crucial contribution of IRE1α to tumor growth, infiltration and invasion and extend the paradigm of secretome control in tumor microenvironment conditioning.

Published
2012

5. Distribution of a Potential p21-Activated Serine/Threonine Kinase (PAK) in Entamoeba histolytica

Author

Philippe J. Sansonetti, Vincent Galy, Elisabeth Labruyère, Nancy Guillén, Pathogénie Microbienne Moléculaire, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by grants from the French Ministère de l'Education Nationale, de l'enseignement Supérieur et de la Recherche, and from the NORD-SUD INSERM programme (Grant No. 4N0016). The confocal microscope used in this work is a gift from M and L Pollack., We thank R Hellio for confocal microscopy assistance., and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH: DNA Primers, MESH: p21-Activated Kinases, [SDV]Life Sciences [q-bio], p21-activated serine/threonine kinase, MESH: Amino Acid Sequence, Protein Serine-Threonine Kinases, MESH: Base Sequence, 03 medical and health sciences, Entamoeba histolytica, 0302 clinical medicine, Animals, MESH: Protein-Serine-Threonine Kinases/metabolism, Distribution (pharmacology), MESH: Animals, Base sequence, Amino Acid Sequence, p21-activated kinases, Peptide sequence, ComputingMilieux_MISCELLANEOUS, DNA Primers, 030304 developmental biology, Serine/threonine-specific protein kinase, 0303 health sciences, Base Sequence, biology, Chemistry, [SDV.BA]Life Sciences [q-bio]/Animal biology, General Medicine, biology.organism_classification, Receptor protein serine/threonine kinase, 3. Good health, p21-Activated Kinases, Biochemistry, PAK, Surface receptor capping, 030220 oncology & carcinogenesis, MESH: Entamoeba histolytica/enzymology
Abstract

International audience

Published
2000

Catalog

Books, media, physical & digital resources
See catalog results