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pi(3,4,5)p3

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https://www.readbyqxmd.com/read/27903653/the-phosphatidylinositol-3-4-5-trisphosphate-pi-3-4-5-p3-binder-rasa3-regulates-phosphoinositide-3-kinase-pi-3-kinase-dependent-integrin-%C3%AE-iib%C3%AE-3-outside-in-signaling
#1
Anthony M Battram, Tom N Durrant, Ejaife O Agbani, Kate J Heesom, David S Paul, Raymond Piatt, Alastair W Poole, Peter J Cullen, Wolfgang Bergmeier, Samantha F Moore, Ingeborg Hers
The class I phosphoinositide 3-kinase (PI 3-kinase) family of lipid kinases plays an important role in integrin αIIbβ3 function, thereby supporting thrombus growth and consolidation. Here, we identify the Ras/Rap1GAP Rasa3 (GAP1IP4BP) as a major phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3)-binding protein in human platelets and a key regulator of integrin αIIbβ3 outside-in signaling. We demonstrate that cytosolic Rasa3 translocates to the plasma membrane in a PI 3kinase-dependent manner upon activation of human platelets...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27897158/iqgap1-makes-pi-3-k-signalling-as-easy-as-pip-pip2-pip3
#2
Lucia E Rameh, Ashley M Mackey
Despite being one of the most studied signalling pathways, precisely how phospholipid synthesis is regulated in the phosphoinositide signalling cascade remains unclear. The scaffold protein IQGAP1 is now shown to orchestrate the assembly of a multi-enzyme complex that streamlines PtdIns(3,4,5)P3 synthesis to facilitate Akt activation in response to extracellular stimuli.
November 29, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27872186/the-interplay-between-calmodulin-and-membrane-interactions-with-the-pleckstrin-homology-domain-of-akt
#3
Constance Agamasu, Ruba H Ghanam, Fei Xu, Yong Sun, Yabing Chen, Jamil S Saad
The Akt protein, a serine/threonine kinase, plays important roles in cell survival, apoptosis and oncogenes. Akt is translocated to the plasma membrane (PM) for activation. Akt-membrane binding is mediated by direct interactions between its pleckstrin homology domain (PHD) and phosphatidylinositol-(3,4,5)-trisphosphate (PI(3,4,5)P3). It has been shown that Akt activation in breast cancer cells is modulated by calmodulin (CaM). However, the molecular mechanism of the interplay between CaM and membrane binding is not established...
November 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27870828/agonist-stimulated-phosphatidylinositol-3-4-5-trisphosphate-generation-by-scaffolded-phosphoinositide-kinases
#4
Suyong Choi, Andrew C Hedman, Samar Sayedyahossein, Narendra Thapa, David B Sacks, Richard A Anderson
Generation of the lipid messenger phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) is crucial for development, cell growth and survival, and motility, and it becomes dysfunctional in many diseases including cancers. Here we reveal a mechanism for PtdIns(3,4,5)P3 generation by scaffolded phosphoinositide kinases. In this pathway, class I phosphatidylinositol-3-OH kinase (PI(3)K) is assembled by IQGAP1 with PI(4)KIIIα and PIPKIα, which sequentially generate PtdIns(3,4,5)P3 from phosphatidylinositol...
November 21, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27819060/the-hidden-conundrum-of-phosphoinositide-signaling-in-cancer
#5
Narendra Thapa, Xiaojun Tan, Suyong Choi, Paul F Lambert, Alan C Rapraeger, Richard A Anderson
Phosphoinositide 3-kinase (PI3K) generation of PI(3,4,5)P3 from PI(4,5)P2 and the subsequent activation of Akt and its downstream signaling cascades (e.g. mTORC1) dominates the landscape of phosphoinositide signaling axis in cancer research. However, PI(4,5)P2 is breaking its boundary as merely a substrate for PI3K and phospholipase C (PLC), and is now an established lipid messenger pivotal for different cellular events in cancer. Here, we review the phosphoinositide signaling axis in cancer, giving due weight to PI(4,5)P2 and its generating enzymes, the phosphatidylinositol phosphate (PIP) kinases (PIPKs)...
July 2016: Trends in Cancer
https://www.readbyqxmd.com/read/27775720/a-neuronal-pi-3-4-5-p3-dependent-program-of-oligodendrocyte-precursor-recruitment-and-myelination
#6
Sandra Goebbels, Georg L Wieser, Alexander Pieper, Sonia Spitzer, Bettina Weege, Kuo Yan, Julia M Edgar, Oleksandr Yagensky, Sven P Wichert, Amit Agarwal, Khalad Karram, Nicolas Renier, Marc Tessier-Lavigne, Moritz J Rossner, Ragnhildur Thóra Káradóttir, Klaus-Armin Nave
The molecular trigger of CNS myelination is unknown. By targeting Pten in cerebellar granule cells and activating the AKT1-mTOR pathway, we increased the caliber of normally unmyelinated axons and the expression of numerous genes encoding regulatory proteins. This led to the expansion of genetically wild-type oligodendrocyte progenitor cells, oligodendrocyte differentiation and de novo myelination of parallel fibers. Thus, a neuronal program dependent on the phosphoinositide PI(3,4,5)P3 is sufficient to trigger all steps of myelination...
October 24, 2016: Nature Neuroscience
https://www.readbyqxmd.com/read/27760174/bar-proteins-pstpip1-2-regulate-podosome-dynamics-and-the-resorption-activity-of-osteoclasts
#7
Martin Sztacho, Sandra Segeletz, Maria Arantzazu Sanchez-Fernandez, Cornelia Czupalla, Christian Niehage, Bernard Hoflack
Bone resorption in vertebrates relies on the ability of osteoclasts to assemble F-actin-rich podosomes that condense into podosomal belts, forming sealing zones. Sealing zones segregate bone-facing ruffled membranes from other membrane domains, and disassemble when osteoclasts migrate to new areas. How podosome/sealing zone dynamics is regulated remains unknown. We illustrate the essential role of the membrane scaffolding F-BAR-Proline-Serine-Threonine Phosphatase Interacting Proteins (PSTPIP) 1 and 2 in this process...
2016: PloS One
https://www.readbyqxmd.com/read/27716613/lipid-phosphatase-ship2-functions-as-oncogene-in-colorectal-cancer-by-regulating-pkb-activation
#8
Elmer Hoekstra, Asha M Das, Marcella Willemsen, Marloes Swets, Peter J K Kuppen, Christien J van der Woude, Marco J Bruno, Jigisha P Shah, Timo L M Ten Hagen, John D Chisholm, William G Kerr, Maikel P Peppelenbosch, Gwenny M Fuhler
Colorectal cancer (CRC) is the second most common cause of cancer-related death, encouraging the search for novel therapeutic targets affecting tumor cell proliferation and migration. These cellular processes are under tight control of two opposing groups of enzymes; kinases and phosphatases. Aberrant activity of kinases is observed in many forms of cancer and as phosphatases counteract such "oncogenic" kinases, it is generally assumed that phosphatases function as tumor suppressors. However, emerging evidence suggests that the lipid phosphatase SH2-domain-containing 5 inositol phosphatase (SHIP2), encoded by the INPPL1 gene, may act as an oncogene...
September 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27698019/ralf-mediated-activation-of-arf6-controls-rickettsia-typhi-invasion-by-co-opting-phosphoinositol-metabolism
#9
Kristen E Rennoll-Bankert, M Sayeedur Rahman, Mark L Guillotte, Stephanie S Lehman, Magda Beier-Sexton, Joseph J Gillespie, Abdu F Azad
Rickettsiae are obligate intracellular pathogens that induce their uptake into non-phagocytic cells; however, the events instigating this process are incompletely understood. Importantly, diverse Rickettsia species are predicted to utilize divergent mechanisms to colonize host cells, as nearly all adhesins and effectors involved in host cell entry are differentially encoded in diverse Rickettsia species. One particular effector, RalF, a sec-7 domain containing protein that functions as a guanine nucleotide exchange factor of ADP-ribosylation factors (Arfs), is critical for R...
October 3, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27563672/association-between-tlr4-and-pten-involved-in-lps-tlr4-signaling-response
#10
Huahua Yin, Yan Tan, Xiaofeng Wu, Hong Yan, Feng Liu, Yuanzhang Yao, Jianxin Jiang, Qi Wan, Lei Li
In this study, we explored the potential mechanisms of how PTEN regulating LPS induced TLR4 signaling pathway. The initial findings from ELISA demonstrate that PTEN influences TNF-α secretion by its lipid phosphatase activity. Subsequently, western blot, immunoprecipitation assay, and immunofluorescence were performed to explore the activation process of PTEN by stimulation with LPS. As early as 20 minutes after LPS stimulation, reduced phosphorylation of PTEN was found obviously. Accordingly, the whole cell-scattered PTEN translocated towards the cell membrane 20 minutes after stimulating with LPS...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27401686/the-joubert-syndrome-protein-inpp5e-controls-ciliogenesis-by-regulating-phosphoinositides-at-the-apical-membrane
#11
Wenyan Xu, Miaomiao Jin, Ruikun Hu, Hong Wang, Fan Zhang, Shiaulou Yuan, Ying Cao
Phosphoinositides, a family of phosphorylated derivatives of phosphatidylinositol (PtdIns), are tightly regulated both temporally and spatially by PtdIns phosphatases and kinases. Mutations in inositol polyphosphate 5-phosphatase E (INPP5E) cause Joubert syndrome, a human disorder associated with numerous ciliopathic defects, including renal cyst formation, linking phosphoinositides to ciliopathies. However, the molecular mechanism by which INPP5E-mediated PtdIns signaling regulates ciliogenesis and cystogenesis is unclear...
July 8, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27271914/multi-state-transition-kinetics-of-intracellular-signaling-molecules-by-single-molecule-imaging-analysis
#12
Satomi Matsuoka, Yukihiro Miyanaga, Masahiro Ueda
The chemotactic signaling of eukaryotic cells is based on a chain of interactions between signaling molecules diffusing on the cell membrane and those shuttling between the membrane and cytoplasm. In this chapter, we describe methods to quantify lateral diffusion and reaction kinetics on the cell membrane. By the direct visualization and statistic analyses of molecular Brownian movement achieved by single-molecule imaging techniques, multiple states of membrane-bound molecules are successfully revealed with state transition kinetics...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27222577/phosphoinositide-5-and-3-phosphatase-activities-of-a-voltage-sensing-phosphatase-in-living-cells-show-identical-voltage-dependence
#13
Dongil Keum, Martin Kruse, Dong-Il Kim, Bertil Hille, Byung-Chang Suh
Voltage-sensing phosphatases (VSPs) are homologs of phosphatase and tensin homolog (PTEN), a phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] 3-phosphatase. However, VSPs have a wider range of substrates, cleaving 3-phosphate from PI(3,4)P2 and probably PI(3,4,5)P3 as well as 5-phosphate from phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and PI(3,4,5)P3 in response to membrane depolarization. Recent proposals say these reactions have differing voltage dependence...
June 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27170292/expression-purification-crystallisation-and-x-ray-crystallographic-analysis-of-a-truncated-form-of-human-src-homology-2-containing-inositol-5-phosphatase-2
#14
Johanne Le Coq, Luis Heredia Gallego, Daniel Lietha
The Src homology 2 containing inositol 5-phosphatase 2 (SHIP2) catalyses the dephosphorylation of the phospholipid phosphatidylinositol 3,4,5-triphosphate (PI(3,4,5)P3) to form PI(3,4)P2. PI(3,4,5)P3 is a key lipid second messenger, which can recruit signalling proteins to the plasma membrane and subsequently initiate numerous downstream signalling pathways responsible for the regulation of a plethora of cellular events such as proliferation, growth, apoptosis and cytoskeletal rearrangements. SHIP2 has been heavily implicated with several serious diseases such as cancer and type 2 diabetes but its regulation remains poorly understood...
June 2016: Protein Journal
https://www.readbyqxmd.com/read/27076519/optogenetic-activation-reveals-distinct-roles-of-pip3-and-akt-in-adipocyte-insulin-action
#15
Yingke Xu, Di Nan, Jiannan Fan, Jonathan S Bogan, Derek Toomre
Glucose transporter 4 (GLUT4; also known as SLC2A4) resides on intracellular vesicles in muscle and adipose cells, and translocates to the plasma membrane in response to insulin. The phosphoinositide 3-kinase (PI3K)-Akt signaling pathway plays a major role in GLUT4 translocation; however, a challenge has been to unravel the potentially distinct contributions of PI3K and Akt (of which there are three isoforms, Akt1-Akt3) to overall insulin action. Here, we describe new optogenetic tools based on CRY2 and the N-terminus of CIB1 (CIBN)...
May 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27063980/identification-of-toxoplasma-tgph1-a-pleckstrin-homology-domain-containing-protein-that-binds-to-the-phosphoinositide-pi-3-5-p2
#16
Wassim Daher, Juliette Morlon-Guyot, Tchilabalo Dilezitoko Alayi, Stan Tomavo, Kai Wengelnik, Maryse Lebrun
The phosphoinositide phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2) plays crucial roles in the maintenance of lysosome/vacuole morphology, membrane trafficking and regulation of endolysosome-localized membrane channel activity. In Toxoplasma gondii, we previously reported that PI(3,5)P2 is essential for parasite survival by controlling homeostasis of the apicoplast, a particular organelle of algal origin. Here, by using a phosphoinositide pull-down assay, we identified TgPH1 in Toxoplasma a protein conserved in many apicomplexan parasites...
May 2016: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/27033077/assessing-pten-subcellular-localization
#17
Anabel Gil, José I López, Rafael Pulido
PTEN subcellular localization is fundamental in the execution of the distinct PTEN biological activities, including not only its PI(3,4,5)P3 phosphatase activity when associated to membranes but also its subcellular compartment-specific interactions with regulatory and effector proteins, including those exerted in the nucleus. As a consequence, PTEN subcellular localization is tightly regulated in vivo by both intrinsic and extrinsic mechanisms. The plasma membrane/nucleus/cytoplasm partitioning of PTEN has been the focus of several studies, both from a mechanistic and from a disease-association point of view...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/26970734/tirf-imaging-of-fc-gamma-receptor-microclusters-dynamics-and-signaling-on-macrophages-during-frustrated-phagocytosis
#18
Jia Lin, Svetlana Kurilova, Brandon L Scott, Elizabeth Bosworth, Bradley E Iverson, Elizabeth M Bailey, Adam D Hoppe
BACKGROUND: Recent evidence indicates that in addition to the T-cell receptor, microclustering is an important mechanism for the activation of the B-cell receptor and the mast cell Fcε-receptor. In macrophages and neutrophils, particles opsonized with immunoglobulin G (IgG) antibodies activate the phagocytic Fcγ-receptor (FcγR) leading to rearrangements of the actin cytoskeleton. The purpose of this study was to establish a system for high-resolution imaging of FcγR microclustering dynamics and the recruitment of the downstream signaling machinery to these microclusters...
March 12, 2016: BMC Immunology
https://www.readbyqxmd.com/read/26916021/new-functions-of-the-inositol-polyphosphate-5-phosphatases-in-cancer
#19
Christophe Erneux, Somadri Ghosh, Ana Raquel Ramos, William's Elong Edimo
Inositol polyphosphate 5-phosphatases act on inositol phosphates and phosphoinositides as substrates. They are 10 different isoenzymes and several splice variants in the human genome that are involved in a series of human pathologies such as the Lowe syndrome, the Joubert and MORM syndromes, breast cancer, glioblastoma, gastric cancer and several other type of cancers. Inositol 5-phosphatases can be amplified in human cancer cells, whereas the 3- and 4- phosphatase tumor suppressor PTEN and INPP4B, repectively are often repressed or deleted...
2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/26862220/emerging-evidence-of-signalling-roles-for-pi-3-4-p2-in-class-i-and-ii-pi3k-regulated-pathways
#20
REVIEW
Phillip T Hawkins, Len R Stephens
There are eight members of the phosphoinositide family of phospholipids in eukaryotes; PI, PI3P, PI4P, PI5P, PI(4,5)P2, PI(3,4)P2, PI(3,5)P2 and PI(3,4,5)P3. Receptor activation of Class I PI3Ks stimulates the phosphorylation of PI(4,5)P2 to form PI(3,4,5)P3. PI(3,4,5)P3 is an important messenger molecule that is part of a complex signalling network controlling cell growth and division. PI(3,4,5)P3 can be dephosphorylated by both 3- and 5-phosphatases, producing PI(4,5)P2 and PI(3,4)P2, respectively. There is now strong evidence that PI(3,4)P2 generated by this route does not merely represent another pathway for removal of PI(3,4,5)P3, but can act as a signalling molecule in its own right, regulating macropinocytosis, fast endophilin-mediated endocytosis (FEME), membrane ruffling, lamellipodia and invadopodia...
February 2016: Biochemical Society Transactions
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