keyword
MENU ▼
Read by QxMD icon Read
search

pi(3,4,5)p3

keyword
https://www.readbyqxmd.com/read/29078297/increased-intracellular-ca-2-concentrations-prevent-membrane-localization-of-ph-domains-through-the-formation-of-ca-2-phosphoinositides
#1
Jin Ku Kang, Ok-Hee Kim, June Hur, So Hee Yu, Santosh Lamichhane, Jin Wook Lee, Uttam Ojha, Jeong Hee Hong, Cheol Soon Lee, Ji-Young Cha, Young Jae Lee, Seung-Soon Lm, Young Joo Park, Cheol Soo Choi, Dae Ho Lee, In-Kyu Lee, Byung-Chul Oh
Insulin resistance, a key etiological factor in metabolic syndrome, is closely linked to ectopic lipid accumulation and increased intracellular Ca(2+) concentrations in muscle and liver. However, the mechanism by which dysregulated intracellular Ca(2+) homeostasis causes insulin resistance remains elusive. Here, we show that increased intracellular Ca(2+) acts as a negative regulator of insulin signaling. Chronic intracellular Ca(2+) overload in hepatocytes during obesity and hyperlipidemia attenuates the phosphorylation of protein kinase B (Akt) and its key downstream signaling molecules by inhibiting membrane localization of pleckstrin homology (PH) domains...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29056325/pten-regulates-pi-3-4-p2-signaling-downstream-of-class-i-pi3k
#2
Mouhannad Malek, Anna Kielkowska, Tamara Chessa, Karen E Anderson, David Barneda, Pınar Pir, Hiroki Nakanishi, Satoshi Eguchi, Atsushi Koizumi, Junko Sasaki, Véronique Juvin, Vladimir Y Kiselev, Izabella Niewczas, Alexander Gray, Alexandre Valayer, Dominik Spensberger, Marine Imbert, Sergio Felisbino, Tomonori Habuchi, Soren Beinke, Sabina Cosulich, Nicolas Le Novère, Takehiko Sasaki, Jonathan Clark, Phillip T Hawkins, Len R Stephens
The PI3K signaling pathway regulates cell growth and movement and is heavily mutated in cancer. Class I PI3Ks synthesize the lipid messenger PI(3,4,5)P3. PI(3,4,5)P3 can be dephosphorylated by 3- or 5-phosphatases, the latter producing PI(3,4)P2. The PTEN tumor suppressor is thought to function primarily as a PI(3,4,5)P3 3-phosphatase, limiting activation of this pathway. Here we show that PTEN also functions as a PI(3,4)P2 3-phosphatase, both in vitro and in vivo. PTEN is a major PI(3,4)P2 phosphatase in Mcf10a cytosol, and loss of PTEN and INPP4B, a known PI(3,4)P2 4-phosphatase, leads to synergistic accumulation of PI(3,4)P2, which correlated with increased invadopodia in epidermal growth factor (EGF)-stimulated cells...
November 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28939768/plasma-membrane-phosphatidylinositol-4-phosphate-and-4-5-bisphosphate-determine-the-distribution-and-function-of-k-ras4b-but-not-h-ras-proteins
#3
Gergö Gulyás, Glória Radvánszki, Rita Matuska, András Balla, László Hunyady, Tamas Balla, Péter Várnai
Plasma membrane (PM) localization of Ras proteins is crucial for transmitting signals upon mitogen stimulation. Posttranslational lipid modification of Ras proteins plays an important role in their recruitment to the PM. Electrostatic interactions between negatively charged PM phospholipids and basic amino acids found in K-Ras4B (K-Ras) but not in H-Ras are important for permanent K-Ras localization to the PM. Here, we investigated how acute depletion of negatively charged PM polyphosphoinositides (PPIns) from the PM alters the intracellular distribution and activity of K- and H-Ras proteins...
September 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28916189/phosphoinositide-5-phosphatase-activities-control-cell-motility-in-glioblastoma-two-phosphoinositides-pi-4-5-p2-and-pi-3-4-p2-are-involved
#4
REVIEW
Ana Raquel Ramos, William's Elong Edimo, Christophe Erneux
Inositol polyphosphate 5-phosphatases or phosphoinositide 5-phosphatases (PI 5-phosphatases) are enzymes that can act on soluble inositol phosphates and/or phosphoinositides (PIs). Several PI 5-phosphatases have been linked to human genetic diseases, in particular the Lowe protein or OCRL which is mutated in the Lowe syndrome. There are 10 different members of this family and 9 of them can use PIs as substrate. One of these substrates, PI(3,4,5)P3 binds to specific PH domains and recruits as effectors specific proteins to signaling complexes...
September 5, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28869677/fibroblasts-derived-from-patients-with-opsismodysplasia-display-ship2-specific-cell-migration-and-adhesion-defects
#5
Somadri Ghosh, Céline Huber, Quentin Siour, Sérgio B Sousa, Michael Wright, Valérie Cormier-Daire, Christophe Erneux
The SH2 domain containing inositol phosphatase 2 (SHIP2) dephosphorylates PI(3,4,5)P3 to generate PI(3,4)P2, a lipid involved in the control of cell migration and adhesion. The INPPL1 gene that encodes SHIP2 has been found to be mutated in several cases of opsismodysplasia (OPS), a rare autosomal recessive chondrodysplasia characterized by growth plate defects and delayed bone maturation. Reported mutations often result in premature stop codons or missense mutations in SHIP2 catalytic domain. SHIP2 biochemical properties are known from studies in cancer cells; its role in endochondral ossification is unknown...
September 4, 2017: Human Mutation
https://www.readbyqxmd.com/read/28792888/structural-basis-for-interdomain-communication-in-ship2-providing-high-phosphatase-activity
#6
Johanne Le Coq, Marta Camacho-Artacho, José Vicente Velázquez, Clara M Santiveri, Luis Heredia Gallego, Ramón Campos-Olivas, Nicole Dölker, Daniel Lietha
SH2-containing-inositol-5-phosphatases (SHIPs) dephosphorylate the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3) and play important roles in regulating the PI3K/Akt pathway in physiology and disease. Aiming to uncover interdomain regulatory mechanisms in SHIP2, we determined crystal structures containing the 5-phosphatase and a proximal region adopting a C2 fold. This reveals an extensive interface between the two domains, which results in significant structural changes in the phosphatase domain...
August 9, 2017: ELife
https://www.readbyqxmd.com/read/28710365/suppression-of-cell-migration-by-phospholipase-c-related-catalytically-inactive-protein-dependent-modulation-of-pi3k-signalling
#7
Satoshi Asano, Yuri Taniguchi, Yosuke Yamawaki, Jing Gao, Kae Harada, Hiroshi Takeuchi, Masato Hirata, Takashi Kanematsu
The metabolic processes of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] into PI(3,4,5)P3 and the subsequent PI(3,4,5)P3 signalling are involved in cell migration. Dysfunctions in the control of this pathway can cause human cancer cell migration and metastatic growth. Here we investigated whether phospholipase C-related catalytically inactive protein (PRIP), a PI(4,5)P2-binding protein, regulates cancer cell migration. PRIP overexpression in MCF-7 and BT-549 human breast cancer cells inhibited cell migration in vitro and metastasis development in vivo...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28659327/phosphoinositide-dependent-enrichment-of-actin-monomers-in-dendritic-spines-regulates-synapse-development-and-plasticity
#8
Wenliang Lei, Kenneth R Myers, Yanfang Rui, Siarhei Hladyshau, Denis Tsygankov, James Q Zheng
Dendritic spines are small postsynaptic compartments of excitatory synapses in the vertebrate brain that are modified during learning, aging, and neurological disorders. The formation and modification of dendritic spines depend on rapid assembly and dynamic remodeling of the actin cytoskeleton in this highly compartmentalized space, but the precise mechanisms remain to be fully elucidated. In this study, we report that spatiotemporal enrichment of actin monomers (G-actin) in dendritic spines regulates spine development and plasticity...
August 7, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28650469/a-compartmentalized-phosphoinositide-signaling-axis-at-cilia-is-regulated-by-inpp5e-to-maintain-cilia-and-promote-sonic-hedgehog-medulloblastoma
#9
S E Conduit, V Ramaswamy, M Remke, D N Watkins, B J Wainwright, M D Taylor, C A Mitchell, J M Dyson
Sonic Hedgehog (SHH) signaling at primary cilia drives the proliferation and progression of a subset of medulloblastomas, the most common malignant paediatric brain tumor. Severe side effects associated with conventional treatments and resistance to targeted therapies has led to the need for new strategies. SHH signaling is dependent on primary cilia for signal transduction suggesting the potential for cilia destabilizing mechanisms as a therapeutic target. INPP5E is an inositol polyphosphate 5-phosphatase that hydrolyses PtdIns(4,5)P2 and more potently, the phosphoinositide (PI) 3-kinase product PtdIns(3,4,5)P3...
October 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28621027/aromatic-amino-acids-and-their-relevance-in-the-specificity-of-the-ph-domain
#10
Ja Morales, M Sobol, L C Rodriguez-Zapata, P Hozak, E Castano
Phosphoinositides are phosphatidylinositol derived, well known to be second messengers in various cell signaling pathways as well as in processes such as cell differentiation, cellular stress response, gene transcription, and chromatin remodeling. The pleckstrin homology domain of phospholipase C-delta 1 is responsible for recognizing and binding to PI(4,5)P2 and for this reason has been widely used to study this phosphoinositide as a biosensor when it is conjugated to a fluorescent tag. In this work, we modified the primary structure of pleckstrin homology domain by site-specific mutagenesis to change the specificity for phosphoinositides...
June 16, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/28572395/mtorc1-activity-repression-by-late-endosomal-phosphatidylinositol-3-4-bisphosphate
#11
Andrea L Marat, Alexander Wallroth, Wen-Ting Lo, Rainer Müller, Giuseppe Danilo Norata, Marco Falasca, Carsten Schultz, Volker Haucke
Nutrient sensing by mechanistic target of rapamycin complex 1 (mTORC1) on lysosomes and late endosomes (LyLEs) regulates cell growth. Many factors stimulate mTORC1 activity, including the production of phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] by class I phosphatidylinositol 3-kinases (PI3Ks) at the plasma membrane. We investigated mechanisms that repress mTORC1 under conditions of growth factor deprivation. We identified phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2], synthesized by class II PI3K β (PI3KC2β) at LyLEs, as a negative regulator of mTORC1, whereas loss of PI3KC2β hyperactivated mTORC1...
June 2, 2017: Science
https://www.readbyqxmd.com/read/28480512/regulation-of-immune-cell-signaling-by-ship1-a-phosphatase-scaffold-protein-and-potential-therapeutic-target
#12
REVIEW
Samantha D Pauls, Aaron J Marshall
The phosphoinositide phosphatase SHIP is a critical regulator of immune cell activation. Despite considerable study, the mechanisms controlling SHIP activity to ensure balanced cell activation remain incompletely understood. SHIP dampens BCR signaling in part through its association with the inhibitory coreceptor Fc gamma receptor IIB, and serves as an effector for other inhibitory receptors in various immune cell types. The established paradigm emphasizes SHIP's inhibitory receptor-dependent function in regulating phosphoinositide 3-kinase signaling by dephosphorylating the phosphoinositide PI(3,4,5)P3 ; however, substantial evidence indicates that SHIP can be activated independently of inhibitory receptors and can function as an intrinsic brake on activation signaling...
June 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28409542/inhibitory-receptor-fc%C3%AE-riib-mediates-the-effects-of-igg-on-a-phagosome-acidification-and-a-sequential-dephosphorylation-system-comprising-ships-and-inpp4a
#13
Tomohiro Segawa, Kaoru Hazeki, Kiyomi Nigorikawa, Atsuko Nukuda, Tomoki Tanizawa, Kenshiro Miyamoto, Shin Morioka, Osamu Hazeki
The relative abundance of phosphoinositide (PI) species on the phagosome membrane fluctuates over the course of phagocytosis. PtdIns(3,4,5)P3 and PtdIns(3,4)P2 rapidly increase in the forming of the phagocytic cup, following which they disappear after sealing of the cup. In the present study, we monitored the clearance of these PI species using the enhanced green fluorescent protein-fused pleckstrin homology domain of Akt, a fluorescence probe that binds both PtdIns(3,4,5)P3 and PtdIns(3,4)P2 in Raw 264.7 macrophages...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28287133/activated-full-length-myosin-x-moves-processively-on-filopodia-with-large-steps-toward-diverse-two-dimensional-directions
#14
Osamu Sato, Hyun Suk Jung, Satoshi Komatsu, Yoshikazu Tsukasaki, Tomonobu M Watanabe, Kazuaki Homma, Mitsuo Ikebe
Myosin-X, (Myo 10), is an unconventional myosin that transports the specific cargos to filopodial tips, and is associated with the mechanism underlying filopodia formation and extension. To clarify the innate motor characteristic, we studied the single molecule movement of a full-length myosin-X construct with leucine zipper at the C-terminal end of the tail (M10(Full)LZ) and the tail-truncated myosin-X without artificial dimerization motif (BAP-M10(1-979)HMM). M10(Full)LZ localizes at the tip of filopodia like myosin-X full-length (M10(Full))...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28247205/the-mechanism-of-jurkat-cells-apoptosis-induced-by-aggregatibacter-actinomycetemcomitans-cytolethal-distending-toxin
#15
Hui-Ping Chen, Lu Li, Xu Chen, Mi-Fang Yang, Yu Ye, Xiao-Qian Wang, Yan Xu
Cytolethal distending toxin (CDT) which is produced by Aggregatibacter actinomycetemcomitans causes apoptosis in lymphocytes. But the specific mechanism is not clear. The aim of our research was to investigate the effect and mechanism during this process. The wild-type CdtA, CdtB, CdtC (CdtA(W), CdtB(W), CdtC(W)) and mutant CdtB (CdtB(M)) were expressed and purified respectively and the purity of each subunit was examined by BandScan software. And the type I deoxyribonuclease and PI-3,4,5-triphosphate (PI-3,4,5-P3, PIP3) phosphatase activity were detected by DNA agarose gel electrophoresis and enzyme-linked immunosorbent assay respectively...
June 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28157504/pi-3-4-5-p3-engagement-restricts-akt-activity-to-cellular-membranes
#16
Michael Ebner, Iva Lučić, Thomas A Leonard, Ivan Yudushkin
Protein kinase B/Akt regulates cellular metabolism, survival, and proliferation in response to hormones and growth factors. Hyperactivation of Akt is frequently observed in cancer, while Akt inactivation is associated with severe diabetes. Here, we investigated the molecular and cellular mechanisms that maintain Akt activity proportional to the activating stimulus. We show that binding of phosphatidylinositol-3,4,5-trisphosphate (PIP3) or PI(3,4)P2 to the PH domain allosterically activates Akt by promoting high-affinity substrate binding...
February 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28130450/small-gtpase-rab8a-recruited-phosphatidylinositol-3-kinase-%C3%AE-regulates-signaling-and-cytokine-outputs-from-endosomal-toll-like-receptors
#17
Adam A Wall, Lin Luo, Yu Hung, Samuel J Tong, Nicholas D Condon, Antje Blumenthal, Matthew J Sweet, Jennifer L Stow
LPS-mediated activation of Toll-like receptor 4 (TLR4) in macrophages results in the coordinated release of proinflammatory cytokines, followed by regulatory mediators, to ensure that this potentially destructive pathway is tightly regulated. We showed previously that Rab8a recruits PI3Kγ for Akt-dependent signaling during TLR4 activation to limit the production of the proinflammatory cytokines IL-6 and IL-12p40 while enhancing the release of the regulatory/anti-inflammatory cytokine IL-10. Here we broaden the array of immune receptors controlled by Rab8a-PI3Kγ and further define the Rab-mediated membrane domains required for signaling...
March 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28105255/pi3k-ship2-pten-pathway-in-cell-polarity-and-hepatitis-c-virus-pathogenesis
#18
REVIEW
Aline Awad, Ama Gassama-Diagne
Hepatitis C virus (HCV) infects hepatocytes, polarized cells in the liver. Chronic HCV infection often leads to steatosis, fibrosis, cirrhosis and hepatocellular carcinoma, and it has been identified as the leading cause of liver transplantation worldwide. The HCV replication cycle is dependent on lipid metabolism and particularly an accumulation of lipid droplets in host cells. Phosphoinositides (PIs) are minor phospholipids enriched in different membranes and their levels are tightly regulated by specific PI kinases and phosphatases...
January 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/27999175/trans-inhibition-of-activation-and-proliferation-signals-by-fc-receptors-in-mast-cells-and-basophils
#19
Odile Malbec, Lydie Cassard, Marcello Albanesi, Friederike Jönsson, David Mancardi, Gaëtan Chicanne, Bernard Payrastre, Patrice Dubreuil, Eric Vivier, Marc Daëron
Allergic and autoimmune inflammation are associated with the activation of mast cells and basophils by antibodies against allergens or auto-antigens, respectively. Both cell types express several receptors for the Fc portion of antibodies, the engagement of which by antigen-antibody complexes controls their responses. When aggregated on the plasma membrane, high-affinity immunoglobulin E (IgE) receptors (FcεRI) and low-affinity IgG receptors (FcγRIIIA in mice, FcγRIIA in humans) induce these cells to release and secrete proinflammatory mediators, chemokines, and cytokines that account for clinical symptoms...
December 20, 2016: Science Signaling
https://www.readbyqxmd.com/read/27998989/inpp5e-regulates-phosphoinositide-dependent-cilia-transition-zone-function
#20
Jennifer M Dyson, Sarah E Conduit, Sandra J Feeney, Sandra Hakim, Tia DiTommaso, Alex J Fulcher, Absorn Sriratana, Georg Ramm, Kristy A Horan, Rajendra Gurung, Carol Wicking, Ian Smyth, Christina A Mitchell
Human ciliopathies, including Joubert syndrome (JBTS), arise from cilia dysfunction. The inositol polyphosphate 5-phosphatase INPP5E localizes to cilia and is mutated in JBTS. Murine Inpp5e ablation is embryonically lethal and recapitulates JBTS, including neural tube defects and polydactyly; however, the underlying defects in cilia signaling and the function of INPP5E at cilia are still emerging. We report Inpp5e(-/-) embryos exhibit aberrant Hedgehog-dependent patterning with reduced Hedgehog signaling. Using mouse genetics, we show increasing Hedgehog signaling via Smoothened M2 expression rescues some Inpp5e(-/-) ciliopathy phenotypes and "normalizes" Hedgehog signaling...
January 2, 2017: Journal of Cell Biology
keyword
keyword
87549
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"