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1

Gregory, Mark, Meng-Xin Yin, Malcolm J. McConville, et al. "Synthesis of Highly Water-Soluble Adamantyl Phosphoinositide Derivatives." Australian Journal of Chemistry 68, no. 4 (2015): 543. http://dx.doi.org/10.1071/ch14543.

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Phosphatidylinositol phosphates are key regulators of cell signalling pathways and membrane trafficking in eukaryotic cells, and there is a need for new chemical probes to further understand how they interact with lipid-binding proteins. Here, the synthesis of phosphatidylinositol phosphate analogues containing adamantyl carboxylic ester groups, in place of the natural lipid side chains, is described. These derivatives are considerably more soluble in water than analogues containing other lipid side chains and do not form large aggregates such as liposomes or micelles. These adamantyl analogue
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Ibrahim, Muktar Musa, Adamu Uzairu, Muhammad Tukur Ibrahim, and Abdullahi Bello Umar. "Modelling PIP4K2A inhibitory activity of 1,7-naphthyridine analogues using machine learning and molecular docking studies." RSC Advances 13, no. 6 (2023): 3402–15. http://dx.doi.org/10.1039/d2ra07382j.

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Boronenkov, Igor V., Joost C. Loijens, Masato Umeda, and Richard A. Anderson. "Phosphoinositide Signaling Pathways in Nuclei Are Associated with Nuclear Speckles Containing Pre-mRNA Processing Factors." Molecular Biology of the Cell 9, no. 12 (1998): 3547–60. http://dx.doi.org/10.1091/mbc.9.12.3547.

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Phosphoinositide signal transduction pathways in nuclei use enzymes that are indistinguishable from their cytosolic analogues. We demonstrate that distinct phosphatidylinositol phosphate kinases (PIPKs), the type I and type II isoforms, are concentrated in nuclei of mammalian cells. The cytosolic and nuclear PIPKs display comparable activities toward the substrates phosphatidylinositol 4-phosphate and phosphatidylinositol 3-phosphate. Indirect immunofluorescence revealed that these kinases were associated with distinct subnuclear domains, identified as “nuclear speckles,” which also contained
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4

Smith, C. D., and K. J. Chang. "Regulation of Brain Phosphatidylinositol-4-phosphate Kinase by GTP Analogues." Journal of Biological Chemistry 264, no. 6 (1989): 3206–10. http://dx.doi.org/10.1016/s0021-9258(18)94052-4.

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Pratt, Clifford, Yue-Jin Liu, Ting-Yi Chu, Karin Melkonian, Burton E. Tropp, and Robert Engel. "Phosphonolipids. 3. Phosphonic acid analogues of phosphatidylinositol and related materials." Canadian Journal of Chemistry 70, no. 8 (1992): 2135–41. http://dx.doi.org/10.1139/v92-268.

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A convergent synthesis of an isosteric phosphonic acid analogue of phosphatidylinositol has been accomplished in which a non-hydrolyzable P—C—C linkage is present in place of the normal P—O—C esteric linkage joining the phosphate and diacylglycerol portions of the molecule. The synthetic route used provides the configuration at each stereogenic center to correspond to that present in the biologically generated phospholipid. In addition, the approach provides asymmetric introduction of acyl functions, placing saturated and unsaturated acyl groups in the terminal and internal positions respectiv
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Morii, Hiroyuki, Tatsuo Okauchi, Hiroki Nomiya, Midori Ogawa, Kazumasa Fukuda, and Hatsumi Taniguchi. "Studies of inositol 1-phosphate analogues as inhibitors of the phosphatidylinositol phosphate synthase in mycobacteria." Journal of Biochemistry 153, no. 3 (2012): 257–66. http://dx.doi.org/10.1093/jb/mvs141.

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7

Graves, J. D., S. C. Lucas, D. R. Alexander, and D. A. Cantrell. "Guanine nucleotide regulation of inositol phospholipid hydrolysis and CD3-antigen phosphorylation in permeabilized T lymphocytes." Biochemical Journal 265, no. 2 (1990): 407–13. http://dx.doi.org/10.1042/bj2650407.

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A method of membrane permeabilization of T lymphocytes with the bacterial cytotoxin streptolysin O has allowed the effect of guanine nucleotide analogues on phosphatidylinositol metabolism and protein kinase C (PKC) activation to be investigated. The data demonstrate that, in permeabilized cells, phosphorylation of the gamma subunit of the CD3 antigen can be induced in response to the PKC activator phorbol 12,13-dibutyrate, the polyclonal mitogen phytohaemagglutinin (PHA) and the stimulatory guanine nucleotide analogue guanosine 5′-[gamma-thio]triphosphate (GTP[S]). Application of a pseudo-sub
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8

Xu, Yong, Stephanie A. Lee, Tatiana G. Kutateladze, Diego Sbrissa, Assia Shisheva, and Glenn D. Prestwich. "Chemical Synthesis and Molecular Recognition of Phosphatase-Resistant Analogues of Phosphatidylinositol-3-phosphate." Journal of the American Chemical Society 128, no. 3 (2006): 885–97. http://dx.doi.org/10.1021/ja0554716.

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9

Taylor, S. J., and J. H. Exton. "Guanine-nucleotide and hormone regulation of polyphosphoinositide phospholipase C activity of rat liver plasma membranes. Bivalent-cation and phospholipid requirements." Biochemical Journal 248, no. 3 (1987): 791–99. http://dx.doi.org/10.1042/bj2480791.

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The effect of the GTP analogue guanosine 5′-[gamma-thio]triphosphate (GTP[S]) on the polyphosphoinositide phospholipase C (PLC) of rat liver was examined by using exogenous [3H]phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]. GTP[S] stimulated the membrane-bound PLC up to 20-fold, with a half-maximal effect at approx. 100 nM. Stimulation was also observed with guanosine 5′-[beta gamma-imido]triphosphate, but not with adenosine 5′-[gamma-thio]triphosphate, and was inhibited by guanosine 5′-[beta-thio]diphosphate. Membrane-bound PLC was entirely Ca2+-dependent, and GTP[S] produced both a d
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10

Lobasso, Simona, Patrizia Lopalco, Roberto Angelini, et al. "Coupled TLC and MALDI-TOF/MS Analyses of the Lipid Extract of the Hyperthermophilic ArchaeonPyrococcus furiosus." Archaea 2012 (2012): 1–10. http://dx.doi.org/10.1155/2012/957852.

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The lipidome of the marine hyperthermophilic archaeonPyrococcus furiosuswas studied by means of combined thin-layer chromatography and MALDI-TOF/MS analyses of the total lipid extract. 80–90% of the major polar lipids were represented by archaeol lipids (diethers) and the remaining part by caldarchaeol lipids (tetraethers). The direct analysis of lipids on chromatography plate showed the presence of the diphytanylglycerol analogues of phosphatidylinositol and phosphatidylglycerol, theN-acetylglucosamine-diphytanylglycerol phosphate plus some caldarchaeol lipids different from those previously
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11

Gold, M. R., J. P. Jakway, and A. L. DeFranco. "Involvement of a guanine-nucleotide-binding component in membrane IgM-stimulated phosphoinositide breakdown." Journal of Immunology 139, no. 11 (1987): 3604–13. http://dx.doi.org/10.4049/jimmunol.139.11.3604.

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Abstract Cross-linking of membrane immunoglobulin, the B cell receptor for antigen, activates the phosphoinositide signal transduction pathway. The initial event in this pathway is the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdInsP2) by phospholipase C. This reaction yields two intracellular second messengers, diacylglycerol, which activates protein kinase C, and inositol trisphosphate, which causes an increase in cytoplasmic Ca2+. The experiments reported here demonstrate that activation of phospholipase C by membrane IgM (mIgM) involves a guanine nucleotide-dependent step. Sapo
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12

Huang, Wei, Honglu Zhang, Foteini Davrazou, et al. "Stabilized Phosphatidylinositol-5-Phosphate Analogues as Ligands for the Nuclear Protein ING2: Chemistry, Biology, and Molecular Modeling." Journal of the American Chemical Society 129, no. 20 (2007): 6498–506. http://dx.doi.org/10.1021/ja070195b.

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13

BRUZIK, K. S., G. LIN, and M. D. TSAI. "ChemInform Abstract: Phosphorothioate Analogues of Phosphatidylinositol and Inositol 1,2- Cyclic Phosphate. Application to the Mechanism of Phospholipase C." ChemInform 23, no. 1 (2010): no. http://dx.doi.org/10.1002/chin.199201338.

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14

Mannix, R. J., T. Moatter, K. A. Kelley, and M. E. Gerritsen. "Cellular signaling responses mediated by a novel nucleotide receptor in rabbit microvessel endothelium." American Journal of Physiology-Heart and Circulatory Physiology 265, no. 2 (1993): H675—H680. http://dx.doi.org/10.1152/ajpheart.1993.265.2.h675.

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The adenine nucleotide, ATP, elicits an elevation in intracellular ionized calcium concentration ([Ca2+]i) and phospholipase C-mediated phosphatidylinositol hydrolysis and stimulates the synthesis of the prostaglandins E2 and I2 in cultured endothelial cells derived from rabbit cardiac muscle. Use of various ATP analogues indicated that these events did not fit the classical definition of P1 or P2 purinergic receptors and, furthermore, indicated that the receptor(s) mediating these activities was not specific for purines. The rank order of agonist potency on prostaglandin release, elevations i
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15

Qiao, Lixin, Fajun Nan, Mark Kunkel, Alfred Gallegos, Garth Powis, and Alan P. Kozikowski. "3-Deoxy-d-myo-inositol 1-Phosphate, 1-Phosphonate, and Ether Lipid Analogues as Inhibitors of Phosphatidylinositol-3-kinase Signaling and Cancer Cell Growth." Journal of Medicinal Chemistry 41, no. 18 (1998): 3303–6. http://dx.doi.org/10.1021/jm980254j.

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Anderson, L., G. Milligan та K. A. Eidne. "Characterization of the gonadotrophin-releasing hormone receptor in αT3-1 pituitary gonadotroph cells". Journal of Endocrinology 136, № 1 (1993): 51—NP. http://dx.doi.org/10.1677/joe.0.1360051.

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ABSTRACT The present study has characterized the gonadotrophin-releasing hormone (GnRH) receptor in immortalized αT3-1 pituitary gonadotroph cells. GnRH and GnRH analogues produced both a dose- and time-dependent increase in total inositol phosphate (IP) accumulation. The rank order of potency of these analogues was the same as that obtained in parallel receptor-binding studies in αT3-1 cells. These responses were abolished following pretreatment with a GnRH antagonist. The use of a specific inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) assay demonstrated a rapid but short-lived rise in Ins(1,4,
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17

Eberhard, D. A., and R. W. Holz. "Regulation of the formation of inositol phosphates by calcium, guanine nucleotides and ATP in digitonin-permeabilized bovine adrenal chromaffin cells." Biochemical Journal 279, no. 2 (1991): 447–53. http://dx.doi.org/10.1042/bj2790447.

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Both micromolar Ca2+ and guanosine 5′-[gamma-thio]triphosphate (GTP[S]) stimulated the formation of inositol phosphates (InsPs) in digitonin-permeabilized chromaffin cells prelabelled with [3H]inositol. The production of InsPs was potentiated by ATP. Guanosine 5′-[beta-thio]diphosphate (GDP[S]) caused a GTP-reversible shift to higher concentrations in the Ca(2+)-concentration-response curve for the release of InsPs without changing the maximal response. GTP[S] caused a shift to lower concentrations of Ca2+ and also increased the maximal response. The effects of GTP[S] and Ca2+ were synergistic
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18

Tamir, A., and N. Isakov. "Cyclic AMP inhibits phosphatidylinositol-coupled and -uncoupled mitogenic signals in T lymphocytes. Evidence that cAMP alters PKC-induced transcription regulation of members of the jun and fos family of genes." Journal of Immunology 152, no. 7 (1994): 3391–99. http://dx.doi.org/10.4049/jimmunol.152.7.3391.

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Abstract T lymphocyte stimulation via the Ag receptor results in activation of phospholipase C gamma 1 that catalyses the hydrolysis of phosphatidylinositol (PI). The hydrolysis generates inositol phosphate and diacylglycerol, which in turn, increase intracellular Ca2+ concentration and activates protein kinase C, respectively. Agonists operating via the adenylate cyclase pathway or cell permeable cAMP analogues inhibit T cell activation by interfering with the PI-turnover. We have shown that dbcAMP inhibits PI-independent mitogenic signals in T cells after stimulation with TPA plus ionomycin.
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19

Faili, A., J. Randon, I. M. Francischetti, B. B. Vargaftig, and M. Hatmi. "Convulxin-induced platelet aggregation is accompanied by a powerful activation of the phospholipase C pathway." Biochemical Journal 298, no. 1 (1994): 87–91. http://dx.doi.org/10.1042/bj2980087.

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Platelet aggregation and stimulation of phosphoinositide-specific phospholipase C (PLC) by thrombin and by convulxin (Cvx), a non-enzymic snake venom glycoprotein, were compared. Cvx-stimulated production of inositol phosphates by washed platelets was independent of the cyclo-oxygenase pathway, formation of platelet-activating factor and ADP release, but prostacyclin (prostaglandin I2), a stimulator of cyclic AMP formation, suppressed its effects on platelet and PLC activation. Kinetic analysis showed that inositol 1,4,5-trisphosphate formation reached its maximal value 15 s after platelet sti
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20

Harnett, M. M., and G. G. Klaus. "G protein coupling of antigen receptor-stimulated polyphosphoinositide hydrolysis in B cells." Journal of Immunology 140, no. 9 (1988): 3135–39. http://dx.doi.org/10.4049/jimmunol.140.9.3135.

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Abstract Cross-linking of the IgM and IgD Ag-R on mature B lymphocytes provokes the rapid hydrolysis of phosphatidylinositol 4,5-bisphosphate. We show here that in permeabilized, [3H]inositol-labeled mouse B cells the nonhydrolyzable GTP analogue GTP gamma S induces release of inositol phosphates, including inositol trisphosphate. The response is markedly augmented by the addition of polyclonal anti-Ig or anti-mu or anti-delta mAb. Inositol phosphate release provoked in intact B cells by any of the anti-receptor antibodies was not inhibited by pertussis toxin and only partially inhibited by ch
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21

Camps, M., C. F. Hou, K. H. Jakobs та P. Gierschik. "Guanosine 5′-[γ-thio]triphosphate-stimulated hydrolysis of phosphatidylinositol 4,5-bisphosphate in HL-60 granulocytes. Evidence that the guanine nucleotide acts by relieving phospholipase C from an inhibitory constraint". Biochemical Journal 271, № 3 (1990): 743–48. http://dx.doi.org/10.1042/bj2710743.

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Myeloid differentiated human leukaemia (HL-60) cells contain a soluble phospholipase C that hydrolysed phosphatidylinositol 4.5-bisphosphate and was markedly stimulated by the metabolically stable GTP analogue guanosine 5′-[gamma-thio]triphosphate (GTP[S]). Half-maximal and maximal (up to 5-fold) stimulation of inositol phosphate formation by GTP[S] occurred at 1.5 microM and 30 microM respectively. Other nucleotides (GTP, GDP, GMP, guanosine 5′-[beta-thio]diphosphate. ATP, adenosine 5′-[gamma-thio]triphosphate, UTP) did not affect phospholipase C activity, GTP[S] stimulation of inositol phosp
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Klima, Martin, Adriana Baumlova, Dominika Chalupska та ін. "The high-resolution crystal structure of phosphatidylinositol 4-kinase IIβ and the crystal structure of phosphatidylinositol 4-kinase IIα containing a nucleoside analogue provide a structural basis for isoform-specific inhibitor design". Acta Crystallographica Section D Biological Crystallography 71, № 7 (2015): 1555–63. http://dx.doi.org/10.1107/s1399004715009505.

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Phosphatidylinositol 4-phosphate (PI4P) is the most abundant monophosphoinositide in eukaryotic cells. Humans have four phosphatidylinositol 4-kinases (PI4Ks) that synthesize PI4P, among which are PI4K IIβ and PI4K IIα. In this study, two crystal structures are presented: the structure of human PI4K IIβ and the structure of PI4K IIα containing a nucleoside analogue. The former, a complex with ATP, is the first high-resolution (1.9 Å) structure of a PI4K. These structures reveal new details such as high conformational heterogeneity of the lateral hydrophobic pocket of the C-lobe and together pr
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Vicentini, L. M., A. Ambrosini, F. Di Virgilio, J. Meldolesi, and T. Pozzan. "Activation of muscarinic receptors in PC12 cells. Correlation between cytosolic Ca2+ rise and phosphoinositide hydrolysis." Biochemical Journal 234, no. 3 (1986): 555–62. http://dx.doi.org/10.1042/bj2340555.

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The intracellular signals generated by carbachol activation of the muscarinic receptor [release of inositol phosphates as a consequence of phosphoinositide hydrolysis and rise of the cytosolic Ca2+ concentration ([Ca2+]i, measured by quin2)] were studied in intact PC12 pheochromocytoma cells that had been differentiated by treatment with nerve growth factor. When measured in parallel samples of the same cell preparation 30 s after receptor activation, the release of inositol trisphosphate and of its possible metabolites, inositol bis- and mono-phosphate, and the [Ca2+]i rise were found to occu
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24

Golla, Rajasree, and Ramakrishna Seethala. "A Homogeneous Enzyme Fragment Complementation Cyclic AMP Screen for GPCR Agonists." Journal of Biomolecular Screening 7, no. 6 (2002): 515–25. http://dx.doi.org/10.1177/1087057102238625.

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In the new high-throughput screening (HTS) campaign, receptor functional assays, 3’,5’-cyclic adenosine mono-phosphate (cAMP), intracellular [Ca2+]i, phosphatidylinositol turnover, and reporter-based assays are being used as primary screens as they are now developed as homogeneous and automation-friendly assays. FlashPlate assay and scintillation proximity assay using radiolabeled cAMP have been used for measuring cAMP. A nonradioactive homogeneous HTS assay using HitHunter™ enzyme fragment complementation (EFC) technology was evaluated for measuring cAMP in adherent and suspension cells overe
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Van Haastert, P. J. M., M. J. De Vries, L. C. Penning та ін. "Chemoattractant and guanosine 5′-[γ-thio]triphosphate induce the accumulation of inositol 1,4,5-trisphosphate in Dictyostelium cells that are labelled with [3H]inositol by electroporation". Biochemical Journal 258, № 2 (1989): 577–86. http://dx.doi.org/10.1042/bj2580577.

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The analysis of the inositol cycle in Dictyostelium discoideum cells is complicated by the limited uptake of [3H]inositol (0.2% of the applied radioactivity in 6 h), and by the conversion of [3H]inositol into water-soluble inositol metabolites that are eluted near the position of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] on anion-exchange h.p.l.c. columns. The uptake was improved to 2.5% by electroporation of cells in the presence of [3H]inositol; electroporation was optimal at two 210 microseconds pulses of 7 kV. Cells remained viable and responsive to chemotactic signals after electroporat
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26

Tokuoka, Suzumi M., Adolfo Saiardi, and Stephen J. Nurrish. "The Mood Stabilizer Valproate Inhibits both Inositol- and Diacylglycerol-signaling Pathways in Caenorhabditis elegans." Molecular Biology of the Cell 19, no. 5 (2008): 2241–50. http://dx.doi.org/10.1091/mbc.e07-09-0982.

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The antiepileptic valproate (VPA) is widely used in the treatment of bipolar disorder, although the mechanism of its action in the disorder is unclear. We show here that VPA inhibits both inositol phosphate and diacylglycerol (DAG) signaling in Caenorhabditis elegans. VPA disrupts two behaviors regulated by the inositol-1,4,5-trisphosphate (IP3): defecation and ovulation. VPA also inhibits two activities regulated by DAG signaling: acetylcholine release and egg laying. The effects of VPA on DAG signaling are relieved by phorbol ester, a DAG analogue, suggesting that VPA acts to inhibit DAG pro
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Smith, C. D., D. Wen, S. L. Mooberry, and K. J. Chang. "Inhibition of phosphatidylinositol 4-phosphate kinase by heparin. A possible mechanism for the antiproliferative effects of heparin." Biochemical Journal 281, no. 3 (1992): 803–8. http://dx.doi.org/10.1042/bj2810803.

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Heparin and related glycosaminoglycans are important modulators of vascular smooth muscle cell growth, and may be involved in pathological processes such as atherosclerosis. Since polyphosphoinositide metabolism is a major mechanism for regulating cellular activities, including proliferation, the effects of glycosaminoglycans and polyanionic compounds on the activities of phosphoinositide kinases were characterized. Heparin and heparan sulphate caused dose-dependent inhibitions of rat brain cytosolic phosphatidylinositol 4-phosphate (PIP) kinase activity, with half-maximal inhibitory concentra
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Putney, J. W. "The role of phosphoinositide metabolism in signal transduction in secretory cells." Journal of Experimental Biology 139, no. 1 (1988): 135–50. http://dx.doi.org/10.1242/jeb.139.1.135.

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Activation of a variety of cell surface receptors results in a biphasic increase in the cytoplasmic Ca2+ concentration, due to the release, or mobilization, of intracellular Ca2+ stores and to the entry of Ca2+ from the extracellular space. Stimulation of these same receptors also results in the phospholipase-C-catalysed hydrolysis of the minor plasma membrane phospholipid, phosphatidylinositol 4,5-bisphosphate, with the concomitant formation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and diacylglycerol. Analogous to the adenylyl cyclase signalling system, receptor-mediated stimulation of
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29

Kolb, J. P., D. Renard, B. Dugas, et al. "Monoclonal anti-CD23 antibodies induce a rise in [Ca2+]i and polyphosphoinositide hydrolysis in human activated B cells. Involvement of a Gp protein." Journal of Immunology 145, no. 2 (1990): 429–37. http://dx.doi.org/10.4049/jimmunol.145.2.429.

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Abstract Transduction through the CD23 molecule (Fc epsilon RII) was analyzed in human activated B lymphocytes using anti-CD23 mAb. B cell blasts expressing an increased amount of surface CD23 molecule were obtained by stimulation of normal peripheral blood B lymphocytes with Staphylococcus aureus strain Cowan I and IL-4. Anti-CD23 mAb were found to trigger polyphosphoinositide hydrolysis in these cells (and also in tumoral B cells expressing spontaneously CD23) and a rise in [Ca2+]i which could be attributed to mobilization from cytoplasmic pools. This increase in [Ca2+]i could be mimicked, w
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Kang, Yuan-Lin, Yi-ying Chou, Paul W. Rothlauf, et al. "Inhibition of PIKfyve kinase prevents infection by Zaire ebolavirus and SARS-CoV-2." Proceedings of the National Academy of Sciences 117, no. 34 (2020): 20803–13. http://dx.doi.org/10.1073/pnas.2007837117.

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Virus entry is a multistep process. It initiates when the virus attaches to the host cell and ends when the viral contents reach the cytosol. Genetically unrelated viruses can subvert analogous subcellular mechanisms and use similar trafficking pathways for successful entry. Antiviral strategies targeting early steps of infection are therefore appealing, particularly when the probability for successful interference through a common step is highest. We describe here potent inhibitory effects on content release and infection by chimeric vesicular stomatitis virus (VSV) containing the envelope pr
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31

Anderson, M. P., and M. J. Welsh. "Isoproterenol, cAMP, and bradykinin stimulate diacylglycerol production in airway epithelium." American Journal of Physiology-Lung Cellular and Molecular Physiology 258, no. 6 (1990): L294—L300. http://dx.doi.org/10.1152/ajplung.1990.258.6.l294.

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Previous studies using phorbol esters and cell-free preparations suggest that protein kinase C (PKC) may regulate Cl- secretion and apical membrane Cl- channels in airway epithelium. To determine whether PKC may be involved in receptor-mediated control of secretion, we measured the mass of diacylglycerol (DAG) generated by two Cl- secretagogues, isoproterenol and bradykinin. Bradykinin increased cellular DAG at concentrations similar to those that increase inositol phosphates, suggesting that bradykinin stimulates phosphatidylinositol hydrolysis, as observed in other systems. Isoproterenol als
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32

Stewart Campbell, A., and Gregory R. J. Thatcher. "Synthesis of an analogue of D,L-MYO-inositol-1,2-cyclic phosphate: inhibition of phosphatidylinositol-specific phospholipase C." Tetrahedron Letters 32, no. 20 (1991): 2207–10. http://dx.doi.org/10.1016/s0040-4039(00)79682-1.

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Apgar, J. R. "Polymerization of actin in RBL-2H3 cells can be triggered through either the IgE receptor or the adenosine receptor but different signaling pathways are used." Molecular Biology of the Cell 5, no. 3 (1994): 313–22. http://dx.doi.org/10.1091/mbc.5.3.313.

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Crosslinking of the IgE receptor on rat basophilic leukemia (RBL) cells using the multivalent antigen DNP-BSA leads to a rapid and sustained increase in the filamentous actin content of the cells. Stimulation of RBL cells through the adenosine receptor also induces a very rapid polymerization of actin, which peaks in 45-60 s and is equivalent in magnitude to the F-actin response elicited through stimulation of the IgE receptor. However, in contrast to the IgE mediated response, which remains elevated for over 30 min, the F-actin increase induced by the adenosine analogue 5'-(N-ethylcarboxamido
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34

Pian, Phillip, Annalisa Bucchi, Richard B. Robinson, and Steven A. Siegelbaum. "Regulation of Gating and Rundown of HCN Hyperpolarization-activated Channels by Exogenous and Endogenous PIP2." Journal of General Physiology 128, no. 5 (2006): 593–604. http://dx.doi.org/10.1085/jgp.200609648.

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The voltage dependence of activation of the HCN hyperpolarization-activated cation channels is shifted in inside-out patches by −40 to −60 mV relative to activation in intact cells, a phenomenon referred to as rundown. Less than 20 mV of this hyperpolarizing shift can be due to the influence of the canonical modulator of HCN channels, cAMP. Here we study the role of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) in HCN channel rundown, as hydrolysis of PI(4,5)P2 by lipid phosphatases is thought to underlie rundown of several other channels. We find that bath application of exogenous PI(4,5)
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35

Dunlop, M. E., and R. G. Larkins. "Muscarinic-agonist and guanine nucleotide activation of polyphosphoinositide phosphodiesterase in isolated islet-cell membranes." Biochemical Journal 240, no. 3 (1986): 731–37. http://dx.doi.org/10.1042/bj2400731.

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Stimulated hydrolysis of the inositol phospholipids phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] was investigated by studying the phosphoinositides produced in a suspended preparation of plasma membranes by transference of 32P from [gamma-32P]ATP. At basal Ca2+ concentration (calculated free Ca2+, 150 nM) phospholipid hydrolysis was stimulated either by the muscarinic agonists carbamoylcholine and bethanecol or by the addition of the non-hydrolysable analogue of GTP, guanosine 5′-[beta gamma-imido]triphosphate [p(NH)ppG]. GTP was without
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CAMPBELL, A. S., and G. R. J. THATCHER. "ChemInform Abstract: Synthesis of an Analogue of D,L-myo-Inositol-1,2-cyclic Phosphate: Inhibition of Phosphatidylinositol-Specific Phospholipase C." ChemInform 23, no. 10 (2010): no. http://dx.doi.org/10.1002/chin.199210229.

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Antonny, Bruno, Joëlle Bigay, and Bruno Mesmin. "The Oxysterol-Binding Protein Cycle: Burning Off PI(4)P to Transport Cholesterol." Annual Review of Biochemistry 87, no. 1 (2018): 809–37. http://dx.doi.org/10.1146/annurev-biochem-061516-044924.

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To maintain an asymmetric distribution of ions across membranes, protein pumps displace ions against their concentration gradient by using chemical energy. Here, we describe a functionally analogous but topologically opposite process that applies to the lipid transfer protein (LTP) oxysterol-binding protein (OSBP). This multidomain protein exchanges cholesterol for the phosphoinositide phosphatidylinositol 4-phosphate [PI(4)P] between two apposed membranes. Because of the subsequent hydrolysis of PI(4)P, this counterexchange is irreversible and contributes to the establishment of a cholesterol
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38

Warburton, D., S. Buckley, and L. Cosico. "P1 and P2 purinergic receptor signal transduction in rat type II pneumocytes." Journal of Applied Physiology 66, no. 2 (1989): 901–5. http://dx.doi.org/10.1152/jappl.1989.66.2.901.

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Extracellular ATP is a potent agonist of surfactant phosphatidylcholine (PC) exocytosis from type II pneumocytes in culture. We studied P1 and P2 receptor signal transduction in type II pneumocytes. The EC50 for ATP on PC exocytosis was 10(-6) M, whereas the EC50 for ADP, AMP, adenosine, and the nonmetabolizable ATP analogue alpha,beta-methylene ATP was 10(-4) M. The rank order of agonists for PC exocytosis was ATP greater than ADP greater than AMP greater than adenosine greater than alpha,beta-methylene ATP. The rank order of agonists for phosphatidylinositol (PI) hydrolysis was ATP greater t
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39

Batty, Ian H., Jeroen van der Kaay, Alex Gray, Joan F. Telfer, Miles J. Dixon, and C. Peter Downes. "The control of phosphatidylinositol 3,4-bisphosphate concentrations by activation of the Src homology 2 domain containing inositol polyphosphate 5-phosphatase 2, SHIP2." Biochemical Journal 407, no. 2 (2007): 255–66. http://dx.doi.org/10.1042/bj20070558.

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Activation of class Ia PI3K (phosphoinositide 3-kinase) produces PtdInsP3, a vital intracellular mediator whose degradation generates additional lipid signals. In the present study vanadate analogues that inhibit PTPs (protein tyrosine phosphatases) were used to probe the mechanisms which regulate the concentrations of these molecules allowing their independent or integrated function. In 1321N1 cells, which lack PtdInsP3 3-phosphatase activity, sodium vanadate or a cell permeable derivative, bpV(phen) [potassium bisperoxo(1,10-phenanthroline)oxovanadate (V)], increased the recruitment into ant
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40

van der Schaar, Hilde M., Pieter Leyssen, Hendrik J. Thibaut та ін. "A Novel, Broad-Spectrum Inhibitor of Enterovirus Replication That Targets Host Cell Factor Phosphatidylinositol 4-Kinase IIIβ". Antimicrobial Agents and Chemotherapy 57, № 10 (2013): 4971–81. http://dx.doi.org/10.1128/aac.01175-13.

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ABSTRACTDespite their high clinical and socioeconomic impacts, there is currently no approved antiviral therapy for the prophylaxis or treatment of enterovirus infections. Here we report on a novel inhibitor of enterovirus replication, compound 1, 2-fluoro-4-(2-methyl-8-(3-(methylsulfonyl)benzylamino)imidazo[1,2-a]pyrazin-3-yl)phenol. This compound exhibited a broad spectrum of antiviral activity, as it inhibited all tested species of enteroviruses and rhinoviruses, with 50% effective concentrations ranging between 4 and 71 nM. After a lengthy resistance selection process, coxsackievirus mutan
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41

Shirai, Y., K. Kashiwagi, N. Sakai, and N. Saito. "Phospholipase A(2) and its products are involved in the purinergic receptor-mediated translocation of protein kinase C in CHO-K1 cells." Journal of Cell Science 113, no. 8 (2000): 1335–43. http://dx.doi.org/10.1242/jcs.113.8.1335.

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The signal transduction involved in the purinergic stimuli-induced activation of protein kinase C (PKC) in CHO-K1 cells was investigated. Purinergic stimuli such as adenosine triphosphate and uridine triphosphate induced a transient translocation of PKC epsilon, gamma, and delta from the cytoplasm to the plasma membrane. These translocations were blocked by an inhibitor of phosphatidylinositol-specific phospholipase C (PLC), but not by an inhibitor of phosphatidylcholine-specific PLC. A diacylglycerol (DAG) analogue also induced reversible translocations of PKC gamma, epsilon, and delta from t
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42

Harrison, D., J. H. Phillips, and L. L. Lanier. "Involvement of a metalloprotease in spontaneous and phorbol ester-induced release of natural killer cell-associated Fc gamma RIII (CD16-II)." Journal of Immunology 147, no. 10 (1991): 3459–65. http://dx.doi.org/10.4049/jimmunol.147.10.3459.

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Abstract Two genes encode the CD16 low affinity IgG FcR. CD16-I (Fc gamma RIII-1) is expressed on PMN as a phosphatidylinositol-glycan anchored glycoprotein. CD16-II (Fc gamma RIII-2) is expressed on NK cells and macrophages as a transmembrane glycoprotein associated with CD3 zeta or Fc epsilon RI-gamma. NK cells spontaneously release soluble CD16-II from the cell surface and this is enhanced by activation with phorbol ester. In this study, we demonstrate that a metalloprotease is involved in the spontaneous and PMA-induced release of CD16-II from NK cells. 1,10-phenanthroline, an inhibitor of
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Zhang, Si Qing, William G. Tsiaras, Toshiyuki Araki, et al. "Receptor-Specific Regulation of Phosphatidylinositol 3′-Kinase Activation by the Protein Tyrosine Phosphatase Shp2." Molecular and Cellular Biology 22, no. 12 (2002): 4062–72. http://dx.doi.org/10.1128/mcb.22.12.4062-4072.2002.

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ABSTRACT Receptor tyrosine kinases (RTKs) play distinct roles in multiple biological systems. Many RTKs transmit similar signals, raising questions about how specificity is achieved. One potential mechanism for RTK specificity is control of the magnitude and kinetics of activation of downstream pathways. We have found that the protein tyrosine phosphatase Shp2 regulates the strength and duration of phosphatidylinositol 3′-kinase (PI3K) activation in the epidermal growth factor (EGF) receptor signaling pathway. Shp2 mutant fibroblasts exhibit increased association of the p85 subunit of PI3K wit
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Melamed, I., G. Wang, and C. M. Roifman. "Antigen receptor-mediated protein tyrosine kinase activity is regulated by a pertussis toxin-sensitive G protein." Journal of Immunology 149, no. 1 (1992): 169–74. http://dx.doi.org/10.4049/jimmunol.149.1.169.

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Abstract Ligation of the Ag receptor on B cells is associated with a rapid increase in phosphorylation on tyrosine residues of multiple substrates. One of the substrates is the phosphoinositide-specific phospholipase C-gamma 1. Because activation of phospholipase C-gamma 1 seems to be dependent on tyrosine phosphorylation, it is assumed that the two signaling pathways, phosphatidylinositol turnover and tyrosine phosphorylation, might be linked. However, since the Ag receptor does not possess a kinase domain, it remains unclear how these signaling pathways are regulated by the Ag receptor. Prev
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45

Ebanks, R., C. Roifman, A. Mellors, and G. B. Mills. "The diacylglycerol analogue, 1,2-sn-dioctanoylglycerol, induces an increase in cytosolic free Ca2+ and cytosolic acidification of T lymphocytes through a protein kinase C-independent process." Biochemical Journal 258, no. 3 (1989): 689–98. http://dx.doi.org/10.1042/bj2580689.

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In this paper, we demonstrate that low concentrations (0.5-2.5 microM) of 1,2-sn-dioctanoylglycerol (DiC8), a potent diacylglycerol used in many previous studies to probe the role of protein kinase C (PKC) in cell activation, cause cytosolic alkalinization of human, mouse and pig T lymphocytes through PKC-mediated activation of the Na+/H+ antiport. However, at higher concentrations (greater than or equal to 12.5 microM), the effect on cytosolic pH (pHi) is reversed, resulting in a marked cytosolic acidification, followed by a gradual return of pHi to baseline values. DiC8 also induces marked c
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46

Chartash, E. K., A. Imai, M. C. Gershengorn, M. K. Crow, and S. M. Friedman. "Direct human T helper cell-induced B cell activation is not mediated by inositol lipid hydrolysis." Journal of Immunology 140, no. 6 (1988): 1974–81. http://dx.doi.org/10.4049/jimmunol.140.6.1974.

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Abstract The Ag-specific interaction between cloned allospecific human Th cells and class II MHC determinants on the surface of allogeneic B cells induces a significant fraction of resting B cells to express a B cell specific activation Ag BLAST-2 (CD23). On the other hand, cross-linking of B cell surface Ig R by Ag analogues does not lead to BLAST-2 expression. By utilizing the BLAST-2 induction assay as a positive control for efficient Th-B cell interaction, we have investigated the biochemical basis of human B cell activation mediated by Ag and Th cells. Our data demonstrate that ligands fo
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Kim, Ji-Eun, Hana Park та Tae-Cheon Kang. "CDDO-Me Distinctly Regulates Regional Specific Astroglial Responses to Status Epilepticus via ERK1/2-Nrf2, PTEN-PI3K-AKT and NFκB Signaling Pathways". Antioxidants 9, № 10 (2020): 1026. http://dx.doi.org/10.3390/antiox9101026.

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2-Cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) is a triterpenoid analogue of oleanolic acid. CDDO-Me shows anti-inflammatory and neuroprotective effects. Furthermore, CDDO-Me has antioxidant properties, since it activates nuclear factor-erythroid 2-related factor 2 (Nrf2), which is a key player of redox homeostasis. In the present study, we evaluated whether CDDO-Me affects astroglial responses to status epilepticus (SE, a prolonged seizure activity) in the rat hippocampus in order to understand the underlying mechanisms of reactive astrogliosis and astroglial apopto
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Lucas, David M., and Larry R. Rohrschneider. "A Novel Spliced Form of SH2-Containing Inositol Phosphatase Is Expressed During Myeloid Development." Blood 93, no. 6 (1999): 1922–33. http://dx.doi.org/10.1182/blood.v93.6.1922.406k21_1922_1933.

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SH2-containing Inositol Phosphatase (SHIP) is a 145 kD protein expressed in hematopoietic cells. SHIP is phosphorylated on tyrosine after receptor binding by several cytokines and has a negative role in hematopoiesis. We cloned a murine complementary DNA (cDNA) sequence for an isoform of SHIP with an internal 183 nucleotide deletion, encoding a protein 61 amino acids shorter than 145 kD SHIP. This deletion eliminates potential SH3-domain binding regions and a potential binding site for the p85 subunit of Phosphatidylinositol 3-Kinase. Using polyclonal anti-SHIP antibodies, we and others have p
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Desai, Trupti, Jill Gigg, Roy Gigg, and Eloisa Martín-Zamora. "The preparation of racemic and enantiomerically pure myo-inositol derivatives as intermediates for the synthesis of phosphatidylinositol 3-, 3,4-bis-, and 3,4,5-tris-phosphates and for the synthesis of analogues of 1d-myo-inositol 1,3,4,5-tetrakisphosphate." Carbohydrate Research 296, no. 1-4 (1996): 97–133. http://dx.doi.org/10.1016/s0008-6215(96)00211-x.

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Chiarini, Francesca, Cecilia Grimaldi, Francesca Ricci, et al. "Dual Inhibition of Phosphatidylinositol 3-Kinase and Mammalian Target of Rapamycin with NVP-BEZ235 as a New Therapeutic Option for T-Cell Acute Lymphoblastic Leukemia." Blood 114, no. 22 (2009): 2025. http://dx.doi.org/10.1182/blood.v114.22.2025.2025.

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Abstract Abstract 2025 Poster Board II-2 Introduction: Recent findings have highlighted that constitutively active phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian Target of Rapamycin (mTOR) signaling is a common feature of T-cell acute lymphoblastic leukemia (T-ALL) where it strongly influences cell proliferation and survival. Pathway activation could be due to several reasons which include Notch1 activation leading to HES1-mediated transcriptional suppression of PTEN gene, PTEN phosphorylation or oxidation, and inactivation of SHIP1 phosphatase. These findings lend compelling weight for th
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