TY - JOUR. T1 - Synthesis of fluorescent phosphatidylinositols using a novel inositol H- phosphonate. AU - Leung, Lawrence W.. AU - Vilchèze, Catherine. AU - Bittman, Robert. PY - 1998/5/7. Y1 - 1998/5/7. N2 - Coupling of 1,2-diradyl-sn-glycerol 5 with the novel inositol H- phosphonate derivative, 6-O-benzyl-2,3:4,5-di-O-isopropylidene-myo-inositol H-phosphonate (3), gave fluorescent analogs of phosphatidylinositol (PtdIns, 1) and PtdIns(4,5)-bisphosphate (PtdIns(4,5)P2, 2). Unlike the corresponding phosphoramidate, 3 was stable at -20 °C for several months, making it a useful intermediate for the synthesis of myo-inositol phospholipids.. AB - Coupling of 1,2-diradyl-sn-glycerol 5 with the novel inositol H- phosphonate derivative, 6-O-benzyl-2,3:4,5-di-O-isopropylidene-myo-inositol H-phosphonate (3), gave fluorescent analogs of phosphatidylinositol (PtdIns, 1) and PtdIns(4,5)-bisphosphate (PtdIns(4,5)P2, 2). Unlike the corresponding phosphoramidate, 3 was stable at -20 °C for several months, ...
The incorporation of 32Pi into phospholamban, troponin I, phosphatidylinositols, and inositol trisphosphates was studied in Langendorff-perfused guinea pig hearts stimulated with isoproterenol. Hearts were perfused with Krebs-Henseleit buffer containing [32P]Pk and freeze-clamped at different times during the positive inotropic response. Exposure of the hearts to 0.1 microM isoproterenol for up to 1 minute was associated with significant (up to threefold) increases in phospholamban and troponin I phosphorylation, but there was no significant increase in 32P incorporation into phospholipids. However, longer exposure (2 minutes or more) to isoproterenol was associated with increases in the degree of 32P labeling of phosphatidylinositols and phosphatidic acid. Examination of 32P labeling of inositol trisphosphates in the same hearts revealed that the radioactivity associated with these compounds decreased with time. The decreases were significant at times of exposure of 2 minutes or longer to ...
PIP2(16:0/16:2(9Z,12Z)) is a phosphatidylinositol bisphosphate. Phosphatidylinositol bisphosphates are acidic (anionic) phospholipids that consist of a phosphatidic acid backbone, linked via the phosphate group to a bisphosphorylated inositol (hexahydroxycyclohexane). Phosphatidylinositol bisphosphates are generated from phosphatidylinositols which are phosphorylated by a number of different kinases that place the phosphate moiety on positions 4 and 5 of the inositol ring, although position 3 can also be phosphorylated. Phosphatidylinositols bisphosphates can have many different combinations of fatty acids of varying lengths and saturation attached at the C-1 and C-2 positions. Fatty acids containing 18 and 20 carbons are the most common. PIP2(16:0/16:2(9Z,12Z)), in particular, consists of one chain of palmitic acid at the C-1 position and one chain of (9Z,12Z-hexadecadienoate) at the C-2 position. The palmitic acid moiety is derived from fish oils, milk fats, vegetable oils and animal fats, ...
PIP3(18:1(9Z)/20:3(8Z,11Z,14Z)) is a phosphatidylinositol trisphosphate. Phosphatidylinositol trisphosphates are acidic (anionic) phospholipids that consist of a phosphatidic acid backbone, linked via the phosphate group to a trisphosphorylated inositol (hexahydroxycyclohexane). Phosphatidylinositol trisphosphates are generated from phosphatidylinositols, which are phosphorylated by a number of different kinases that place the phosphate moiety on positions 4 and 5 of the inositol ring, although position 3 can also be phosphorylated. Phosphatidylinositols trisphosphates can have many different combinations of fatty acids of varying lengths and saturation attached at the C-1 and C-2 positions. Fatty acids containing 18 and 20 carbons are the most common. PIP3(18:1(9Z)/20:3(8Z,11Z,14Z)), in particular, consists of one chain of oleic acid at the C-1 position and one chain of homo-g-linolenic acid at the C-2 position. The oleic acid moiety is derived from vegetable oils, especially olive and canola ...
In isolated rat hepatocytes, vasopressin evoked a large increase in the incorporation of [32P]Pi into phosphatidylinositol, accompanied by smaller increases in the incorporation of [1-14C]oleate and [U-14C]glycerol. Incorporation of these precursors into the other major phospholipids was unchanged during vasopressin treatment. Vasopressin also promoted phosphatidylinositol breakdown in hepatocytes. Half-maximum effects on phosphatidylinositol breakdown and on phosphatidylinositol labelling occurred at about 5 nM-vasopressin, a concentration at which approximately half of the hepatic vasopressin receptors are occupied but which is much greater than is needed to produce half-maximal activation of glycogen phosphorylase. Insulin did not change the incorporation of [32P]Pi into the phospholipids of hepatocytes and it had no effect on the response to vasopressin. Although the incorporation of [32P]Pi into hepatocyte lipids was decreased when cells were incubated in a Ca2+-free medium, vasopressin ...
immune Uncategorized PP121, Rabbit polyclonal to BMPR2 Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that regulate diverse cellular procedures including PP121 proliferation adhesion success and motility. III tests in individuals with advanced indolent non-Hodgkins lymphoma and mantle cell lymphoma. With this review we summarized the main substances of PI3K signaling pathway and talked about the preclinical versions and clinical tests of powerful small-molecule PI3K inhibitors. Intro Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that play central part in rules of cell routine apoptosis DNA restoration senescence angiogenesis mobile rate of metabolism and motility [1]. They become intermediate signaling substances PP121 and are renowned for their jobs in the PI3K/AKT/mTOR signaling pathway [2 3 PI3Ks transmit indicators through the cell surface towards the cytoplasm by producing second messengers - phosphorylated phosphatidylinositols - which activate multiple effector ...
Abbreviations: CAPS, calcyphosine; CISK, cytokine-independent survival kinase; DAG, diacylglycerol; DCV, dense core vesicle; DGK, DAG kinase; EEA1, early endosomal antigen 1; ENTH, epsin N-terminal homology; ER, endoplasmic reticulum; IP3, myo-inositol 1,4,5-trisphosphate; LUV, large unilamellar vesicle; NSF, N-ethylmaleimide-sensitive factor; PH domain, pleckstrin homology domain; PI3K, phosphoinositide 3-kinase; PIP, phosphoinositide phosphate; PIP5K, PtdIns4P 5-kinase; PKC, protein kinase C; PLA, phospholipase A; PLC, phospholipase C; PLD, phospholipase D; PI-PLC, phosphoinositide-specific PLC; PtdOH, phosphatidic acid; PX domain, Phox homology domain; SARA, Smad anchor for receptor activation; SNAP, soluble NSF-attachment protein; SNARE, SNAP receptor; SCAMP2, secretory carrier membrane protein 2; VAMP, vesicle-associated membrane protein ...
Phosphatidylinositol-4,5-bisphosphate 3-kinase (also called phosphatidylinositol 3-kinase (PI3K)) is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate phosphatidylinositols (PtdIns), PtdIns4P and PtdIns(4,5)P2.[7] The involvement of p110α in human cancer has been hypothesized since 1995. Support for this hypothesis came from genetic and functional studies, including the discovery of common activating PIK3CA missense mutations in common human tumors.[8] It has been found to be oncogenic and is implicated in cervical cancers.[9] PIK3CA mutations are present in over one-third of breast cancers, with enrichment in the luminal and in human epidermal growth factor receptor 2-positive subtypes (HER2 +). The three hotspot mutation positions (GLU542, GLU545, and HIS1047) have been widely reported till date.[10] While substantial preclinical data show an association with robust ...
Recent literature has shown that buffers affect the interaction between lipid bilayers through a mechanism that involves van der Waals forces, electrostatics, hydration forces and membrane bending rigidity. This talk will highlight our recent work that shows phase coexistence can be a result of Goods buffer charges on the mixed chain 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayers. Since the two phases must be in osmotic equilibrium with one another, this behavior challenges theoretical models of lipid interactions and introduces new variables to consider for the Gibbs phase rule. This model of lipid charging was then used to explain the mechanisms behind phase separation in lipid mixtures containing charged lipid head groups, particularly phosphatidylinositols. Furthermore, this work is then applied to our understanding of underlying mechanisms involved in membrane protein selective association with phosphoinositols, and later re-organization of these membranes. This work ...
Description: A complex mixture of PHOSPHOLIPIDS; GLYCOLIPIDS; and TRIGLYCERIDES; with substantial amounts of PHOSPHATIDYLCHOLINES; PHOSPHATIDYLETHANOLAMINES; and PHOSPHATIDYLINOSITOLS, which are sometimes loosely termed as 1,2-diacyl-3-phosphocholines. Lecithin is a component of the CELL MEMBRANE and commercially extracted from SOYBEANS and EGG YOLK. The emulsifying and surfactant properties are useful in FOOD ADDITIVES and for forming organogels (GELS ...
A complex mixture of phospholipids; glycolipids; and triglycerides; with substantial amounts of phosphatidylcholines; phosphatidylethanolamines; and phosphatidylinositols, which are sometimes loosely termed as 1,2-diacyl-3-phosphocholines. Lecithin is a component of the cell ...
Inositol phospholipids are well known for their pivotal role in calcium signaling as precursors of important second messengers generated in response to various stimuli. However, over the last 10 years, inositides have also emerged as universal signaling components present in virtually every membrane of eukaryotic cells. These lipids are locally produced and degraded by the numerous inositide kinase and phosphatase enzymes, to control the recruitment and activity of protein signaling complexes in specific membrane compartments. The spatial and temporal constraints imposed on changes in cellular inositides pose new challenges in finding experimental techniques through which such changes can be examined. Taking advantage of the protein domains selected by evolution to recognize cellular phosphoinositides, we have created fluorescent molecules by fusing these domains to the improved version of green fluorescent protein (EGFP); the distribution of these fusion proteins can be followed within live ...
The yeast Efr3p protein is a major regulator of the Stt4p phosphatidylinositol 4-kinase at ER-PM contact sites. Its mutant fly homologue, Rbo displays diminishing light responses attributed to progressively impaired PLC signaling. Here we find that Efr3s play a role in maintaining responsiveness to angiotensin II (AngII) receptors. RNAi-mediated depletion of EFR3A and EFR3B impaired the sustained phase of cytosolic Ca2+ response to high concentration of AngII in HEK293 cells expressing the wild type but not a truncated AT1a receptor, missing the phosphorylation sites. Efr3 depletion had minimal effect on the recovery of plasma membrane phosphoinositides during stimulation, and AT1 receptors still underwent ligand-induced internalization. A higher level of basal receptor phosphorylation and a larger response was observed after stimulation. Moreover, Gq activation more rapidly desensitized after AngII stimulation in Efr3 downregulated cells. Similar but smaller effect of EFR3 depletion was ...
PIK3CA [ENSP00000263967]. Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha; Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4- phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5- bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Breakdown products of phosphoinositides are ubiquitous second messengers that function downstream of many G protein-coupled receptors and tyrosine kinases regulating cell growth, calcium metabolism, and protein kinase C activity. This gene encodes an enzyme which regulates the amount of phosphatidylinositol available for signaling by catalyzing the conversion of phosphatidic acid to CDP-diacylglycerol. This enzyme is an integral membrane protein localized to two subcellular domains, the matrix side of the inner mitochondrial membrane where it is thought to be involved in the synthesis of phosphatidylglycerol and cardiolipin and the cytoplasmic side of the endoplasmic reticulum where it functions in phosphatidylinositol biosynthesis. Two genes encoding this enzyme have been identified in humans, one mapping to human chromosome 4q21 and a second to 20p13. [provided by RefSeq, Jul 2008 ...
Pleckstrin homology (PH) domains are small protein modules known for their ability to bind phosphoinositides and to drive membrane recruitment of their host proteins. We investigated phosphoinositide binding (in vitro and in vivo) and subcellular localization, and we modeled the electrostatic proper …
Lipid components in biological membranes are essential for maintaining cellular function. Phosphoinositides, the phosphorylated derivatives of phosphatidylinositol (PI), regulate many critical cell processes involving membrane signaling, trafficking, and reorganization. Multiple metabolic pathways including phosphoinositide kinases and phosphatases and phospholipases tightly control spatio-temporal concentration of membrane phosphoinositides. Metabolizing enzymes responsible for PI 4,5-bisphosphate (PI(4,5)P2) production or degradation play a regulatory role in Toll-like receptor (TLR) signaling and trafficking. These enzymes include PI 4-phosphate 5-kinase, phosphatase and tensin homolog, PI 3-kinase, and phospholipase C. PI(4,5)P2 mediates the interaction with target cytosolic proteins to induce their membrane translocation, regulate vesicular trafficking, and serve as a precursor for other signaling lipids. TLR activation is important for the innate immune response and is implicated in ...
The stimulation of phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis is a widespread cellular response to many hormones, growth factors and neurotransmitters (Berridge 1987). It is catalyzed by...
Many cellular reactions involve both hydrophobic and hydrophilic molecules that reside within the chemically distinct environments defined by the phospholipid-based membranes and the aqueous lumens of cytoplasm and organelles.. Enzymes performing this type of reaction are required to access a lipophilic substrate located in the membranes and to catalyze its reaction with a polar, water-soluble compound. Here we focus on two enzymes involved in the early steps of the phosphatidylinositol mannosides (PIMs) biosynthetic pathway, unique glycolipids found in abundant quantities in the inner and outer membranes of the cell envelope of all Mycobacterium species. They are based on a phosphatidylinositol lipid anchor carrying one to six mannose residues and up to four acyl chains. PIMs are considered not only essential structural components of the cell envelope but also the structural basis of the lipoglycans lipomannan and lipoarabinomannan, important molecules implicated in host-pathogen interactions ...
Nahorski, S. R., Batty, I. H., Willcocks, A. L., Strupish, J. and Potter, B. V. L., 1989. Receptor-mediated phosphoinositide metabolism in brain. In: Segawa, T., Endo, M., Ui, M. and Kurihara, K., eds. Physiology and Pharmacology of Transmembrane Signalling. ...
TY - JOUR. T1 - The regulation of membrane to cytosol partitioning of signalling proteins by phosphoinositides and their soluble headgroups. AU - Downes, C Peter. AU - Gray, Alexandra. AU - Fairservice, A. AU - Safrany, S T. AU - Batty, Ian H. AU - Fleming, Ian Neil. PY - 2005/12. Y1 - 2005/12. N2 - Inositol phospholipids [PIs (phosphoinositides)] represent a group of membrane-tethered signalling molecules which differ with respect to the number and distribution of monoester phosphate groups around the inositol ring. They function by binding to proteins which possess one of several domains that bind a particular PI species, often with high affinity and specificity. PH (pleckstrin homology) domains for example possess ligand-binding pockets that are often lined with positively charged residues and which bind PIs with varying degrees of specificity. Several PH domains bind not only PIs, but also their cognate headgroups, many of which occur naturally in cells as relatively abundant cytosolic ...
The regulation of the synthesis of PtdIns(4,5)P2 is emerging as being as complex as we might expect from the multi-functional nature of this lipid. In the present chapter we focus on one aspect of inositide metabolism, which is the functions of the Type II PIPkins (Type II PtdInsP kinases). These are primarily PtdIns5P 4-kinases, although in vitro they will also phosphorylate PtdIns3P to PtdIns(3,4)P2. Thus they have three, not necessarily exclusive, functions: to make PtdIns(4,5)P2 by a quantitatively minor route, to remove PtdIns5P and to make PtdIns(3,4)P2 by a route that does not involve a Class I PtdIns 3-kinase. None of these three possible functions has yet been unambiguously proven or ruled out. Of the three isoforms, α and β are widely expressed, the IIα being predominantly cytosolic and the IIβ primarily nuclear. PIPkin IIγ has a much more restricted tissue expression pattern, and appears to be localized primarily to intracellular vesicles. Here we introduce in turn each of the ...
When cancer strikes, with many forms, researchers will see alterations in lipid metabolism. While this relationship is known, scientists still dont fully understand how lipids contribute to cellular transformations, tumour development and cancer spread.. At Ryerson, a research group in the Department of Chemistry and Biology set out to study one particular type of lipid, namely signaling phospholipids, also referred to as phosphoinositides. Leslie Bone, a student who is currently completing her PhD in Molecular Science at Ryerson, has dedicated her studies to learning more about how fats communicate within cells and how they can be involved in cancer progression. She was also the lead author of the phosphoinositides study, supervised by two Ryerson professors, Dr. Roberto Botelho and Dr. Costin Antonescu.. Asked to further explain the role of tiny signaling phospholipids, Bone says: Phosphoinositides are important for cellular processes such as cell migration and cell growth. The function of ...
Online Cover This week features a Research Article that identifies ARAP3 as the downstream effector of phosphoinositide 3-kinase (PI3K) in the regulation of sprouting angiogenesis during development. The image shows a wild-type mouse embryo stained for a marker of vascular endothelial cells. [Image: Laure Gambardella, Inositide Laboratory, The Babraham Institute] ...
myo-lnositol (ml), a simple polyol isomer of glucose, is an important osmolyte in the brain and a precursor of the phosphatidyl inositol metabolic pathway. It is known to facilitate various cellular events such as membrane ...
The effect of oxytocin on phosphoinositide metabolism as well as on membrane protein phosphorylation in myometrial tissue was studied. Oxytocin enhanced the 32P incorporation into phospholipids in myometrial tissue. The effect of oxytocin on phosphoinositide metabolism was also detected in plasma membrane of 20 days pregnant rats. Phosphorylated membrane lipids have been analysed and phosphatidylinositol 4, 5-bisphosphate proved to be the main reaction product. Oxytocin enhanced the 32P incorporation into phospholipids measured in the first 30 sec then the labeling decreased more rapidly then in case of the control. The effect of oxytocin proved to be concentration dependent. The protein phosphorylation was also influenced by oxytocin. However the amount of alkylphosphate formed depended on the presence or absence of Ca2+, Ca2+-calmodulin and cyclic AMP, oxytocin influenced the protein phosphorylation in the presence of Ca2+-calmodulin only.
Hi everyone. Im having trouble finding good figures to explain the detailed structure of amphiphilic molecules such as glycerophospholipids, sphingolipids, phosphatidylinositols, phosphatidylcholine, and sterols to a group of high school students taking an early college course in Biology. If anyone knows where to find some without breaking copyright laws (because I would like to post them online) please let me know. Thanks ...
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TY - JOUR. T1 - Regional development of carbachol-, glutamate-, norepinephrine-, and serotonin-stimulated phosphoinositide metabolism in rat brain. AU - Balduini, Walter. AU - Candura, Stefano M.. AU - Costa, Lucio G.. PY - 1991/9/19. Y1 - 1991/9/19. N2 - Phosphoinositide metabolism stimulated by activation of cholinergic muscarinic, glutamatergic, α-adrenergic and serotoninergic receptors was measured in brain regions of the developing rats. Accumulation of [3H]inositol phosphates ([3H]InsPs) in [3H]inositol-prelabeled slices from cerebral cortex, hippocampus, brainstem and cerebellum was measured as an index of phosphoinositide metabolism. Large age-, neurotransmitter receptor-, and brain region-dependent differences were found. Carbachol-stimulated [3H]InsPs accumulation peaked on postnatal day 7 in cerebral cortex and hippocampus while in cerebellum and brainstem the effect of muscarinic stimulation was maximal at birth and then declined to adulthood. The effect of glutamate also showed a ...
Lipid droplet (LD) utilization is an important cellular activity that regulates energy balance and release of lipid second messengers. Because fatty acids exhibit both beneficial and toxic properties, their release from LDs must be controlled. Here we demonstrate that yeast Sfh3, an unusual Sec14-like phosphatidylinositol transfer protein, is an LD-associated protein that inhibits lipid mobilization from these particles. We further document a complex biochemical diversification of LDs during sporulation in which Sfh3 and select other LD proteins redistribute into discrete LD subpopulations. The data show that Sfh3 modulates the efficiency with which a neutral lipid hydrolase-rich LD subclass is consumed during biogenesis of specialized membrane envelopes that package replicated haploid meiotic genomes. These results present novel insights into the interface between phosphoinositide signaling and developmental regulation of LD metabolism and unveil meiosis-specific aspects of Sfh3 (and ...
Phosphoinositide lipids recruit proteins to the plasma membrane involved in the regulation of cytoskeleton organization and in signalling pathways that control cell polarity and growth. Among those, Rgd1p is a yeast GTPase-activating protein (GAP) specific for Rho3p and Rho4p GTPases, which control actin polymerization and stress signalling pathways. Phosphoinositides not only bind Rgd1p, but also stimulate its GAP activity on the membrane-anchored form of Rho4p. Both F-BAR (F-BAR FCH, and BAR) and RhoGAP domains of Rgd1p are involved in lipid interactions. In the Rgd1p-F-BAR domain, a phosphoinositide-binding site has been recently characterized. We report here the X-ray structure of the Rgd1p-RhoGAP domain, identify by NMR spectroscopy and confirm by docking simulations, a new but cryptic phosphoinositide-binding site, comprising contiguous A1, A1′ and B helices. The addition of helix A1′, unusual among RhoGAP domains, seems to be crucial for lipid interactions. Such a site was totally ...
Phosphoinositide signalling regulates a series of important neuronal processes that are thought to be altered in mood disorders. Furthermore, mood-stabilizing drugs inhibit key enzymes that regulate phosphoinositide production and alter neuronal growth cone morphology in an inositol-reversible manner. Inositol is taken up by neurons from the extracellular fluid, presumably via membrane transporters; it can also be synthesized by the enzyme MIP-synthase (myo-inositol-1-phosphate synthase) and, in addition, it is generated by inositol phospholipid hydrolysis. The neuronal-specific HMIT (H+-myo-inositol transporter) represents a potential regulator of inositol signalling in neurons that warrants further investigation.. ...
TY - JOUR. T1 - Mechanism of thrombin-induced arachidonic acid release in osteoblast-like cells. AU - Suzuki, A.. AU - Kozawa, O.. AU - Shinoda, J.. AU - Watanabe-Tomita, Y.. AU - Saito, H.. AU - Oiso, Y.. PY - 1997/6. Y1 - 1997/6. N2 - In a previous study, we have reported that thrombin stimulates phosphatidylcholine hydrolysis by phospholipase (PL) D, but has little effect on phosphoinositide hydrolysis by PLC in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the mechanism of the thrombin-induced arachidonic acid (AA) release in MC3T3-E1 cells. Thrombin stimulated AA release dose dependently in the range between 0.1 and 1 U/ml. Quinacrine, a PLA2 inhibitor, suppressed the thrombin-induced AA release. In addition, quinacrine also suppressed the thrombin-induced prostaglandin E2 synthesis in these cells. On the other hand, propranolol, which is known to inhibit phosphatidic acid phosphohydrolase, did not affect the thrombin-induced AA release. ...
We have purified a 38 kDa protein from bovine brain which is cross-reactive with an affinity purified antibody against the 35 kDa phosphatidylino-sitol transfer protein from the same source. Controlled trypsinization of the 38 kDa protein yielded an immunoreactive protein of 35 kDa which displayed a 6-fold increase in phosphatidylinositol transfer activity and a IO-fold higher affinity for this phospholipid. The possibility that the 38 kDa protein is a precursor of the phosphatidylinositol transfer protein is discussed.(C) 1990 Elsevier Science B.V. All rights reserved ...
Has phosphatidylinositol transfer activity. Involved in the regulation of the phospholipid composition of plasma- and endomembranes. Altering plasma membrane composition may provide a possible mechanism for multidrug resistance. Involved in the regulation of sterol biosynthesis. Contributes to efficient phospholipase D1 activation in the regulation of phospholipid turnover.
The control of proliferation and apoptosis by cytokines is critical in the regulation of a variety of hematopoietic lineages (15, 21). Our data demonstrate PI3K signaling to be indispensable in mediating cellular proliferation and survival. The importance of PI3K activity in mediating survival was supported by overexpression the 3-phosphatidylinositol lipid phosphatase PTEN (36), which is a uniquely specific tool for decreasing 3-phosphoinositide levels in cells. Upon overexpression of membrane-localized PTEN, we observed an induction of apoptosis in IL-3-cultured Ba/F3 cells (Fig. 1C). The fact that membrane-targeted PTEN, unlike wild-type PTEN, is potently active (Fig. 1C) suggests that membrane localization is a critical aspect of PTEN regulation in vivo. Mutations in the chromosomal region of PTEN resulting in a loss of function of PTEN have been described in a variety of neoplasias, including lymphoid malignancies (19). These mutations result in the accumulation of PtdIns(3,4,5)P3 in the ...
Sorting nexin 27 (SNX27) controls the endosomal to cell-surface recycling of diverse transmembrane protein cargos. Critical to this function is the recruitment of SNX27 to endosomes through the binding of phosphatidylinositol-3-phosphate (PtdIns3P) by the phox-homology (PX) domain. In T cells, SNX27 is polarized to the immunological synapse (IS) in an activation-dependent manner, but the molecular mechanisms underlying SNX27 translocation remain to be clarified. Here, we examined the phosphoinositide lipid-binding capabilities of full-length SNX27, and discovered a novel PtdInsP binding site within the C-terminal 4.1/ezrin/radixin/moesin (FERM) domain. This binding site showed a clear preference for di and tri-phosphorylated phophoinositides, and the interaction was confirmed through biophysical, mutagenesis and modeling approaches. At the IS of activated T-cells cell signaling regulates phosphoinositide dynamics, and we find that perturbing phosphoinositide binding by the SNX27 FERM domain ...
CD59, an 18-20-kD complement inhibitor anchored to the membrane via glycosyl phosphatidylinositol (GPI), can induce activation of T cells and neutrophils upon cross-linking with antibody. GPI-anchored molecules cocluster in high mol wt detergent-resistant complexes containing tyrosine kinases that are implicated in the signaling pathway. Exogenous, incorporated GPI-anchored molecules are initially unable to induce activation, presumably because they are not associated with kinases. Here we demonstrate that erythrocyte-derived CD59 incorporated in a CD59-negative cell line acquires signaling capacity in a time-dependent manner. Confocal microscopy revealed an initial diffuse distribution of CD59 that became clustered within 2 h to give a pattern similar to endogenous GPI-anchored molecules. Gel filtration of detergent-solubilized cells immediately after incorporation revealed that CD59 was mainly monomeric, but after 3 h incubation all was in high mol wt complexes and had become associated with ...
Pleckstrin homology domain. Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids. ...
A phosphoinositide present in all eukaryotic cells, particularly in the plasma membrane. It is the major substrate for receptor-stimulated phosphoinositidase C, with the consequent formation of inositol 1,4,5-triphosphate and diacylglycerol, and probably also for receptor-stimulated inositol phospholipid 3-kinase. (Kendrew, The Encyclopedia of Molecular Biology, 1994 ...
These studies document an important role for Tyr348 of the α1B-AR in agonist binding, in functional coupling to PI hydrolysis and Ca2+ mobilization, and in agonist-induced internalization of the receptor. Mutation of Tyr348 to alanine increased agonist binding affinity by ∼10-fold, without altering antagonist binding. This mutation also essentially completely eliminated agonist-induced stimulation of PI hydrolysis and elevation of intracellular Ca2+. Agonist-induced conversion of receptors to a form that is inaccessible to the lipophilic radioligand [3H]prazosin in intact cell binding assays on ice occurred to a similar or greater extent for the Y348A receptor as for the wild-type receptor. In contrast, agonist-induced redistribution of receptors from the plasma membrane fraction to the light vesicle fraction in sucrose density gradient centrifugation assays occurred for the wild-type receptor but not for the Y348A receptor.. Two important conclusions regarding α1B-AR internalization follow ...
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Enzyme immunoassay for the quantitative measurement of IgG and IgM class autoantibodies against phosphatidyl inositol in human serum or plasma
PITPNB antibody, Internal (phosphatidylinositol transfer protein beta) for WB. Anti-PITPNB pAb (GTX45365) is tested in Human samples. 100% Ab-Assurance.
In 2001, Cerivastatin, a drug used to lower cholesterol, was abruptly withdrawn from the market. The drug was not found to cause any problems during its preclinical trials on mice, but when given to humans, it caused 52 fatal cases of a condition called rhabdomyolysis, the rapid breakdown of skeletal muscle tissue. Animal testing had…
Remember how I told you when I joined Crossfit they had me sign something about me possibly dying? Well, hey, MORE INFO ON THAT HERE. Its better known by Crossfitters as Uncle Rhabdo, and its definitely serious shit. Rhabdo is short for rhabdomyolysis, a rapid breakdown of muscle fibers that can occur when the body…
Phosphoinositides (PIs) are minor components on cytoplasmic sides of eukaryotic cell membranes, but they play important roles in many...
Morita YS, Sena CBC, Waller RF, Kurokawa K, Sernee FM, Nakatani F, Haites RE, Billman-Jacobe H, McConville MJ, Maeda Y et al.. 2006. PimE is a polyprenol-phosphate-mannose-dependent mannosyltransferase that transfers the fifth mannose of phosphatidylinositol mannoside in mycobacteria.. J Biol Chem. 281(35):25143-55. ...
Morita YS, Sena CBC, Waller RF, Kurokawa K, Sernee FM, Nakatani F, Haites RE, Billman-Jacobe H, McConville MJ, Maeda Y et al.. 2006. PimE is a polyprenol-phosphate-mannose-dependent mannosyltransferase that transfers the fifth mannose of phosphatidylinositol mannoside in mycobacteria.. J Biol Chem. 281(35):25143-55. ...
Trouvez tous les livres de Stenmark, Harald (ed.) - Phosphoinositides in Subcellular Targeting and Enzyme Activation. Sur eurolivre.fr,vous pouvez commander des livres anciens et neufs.COMPARER ET acheter IMMÉDIATEMENT au meilleur prix. 9783540009504
Inhibition of PDGF-induced phosphoinositide turnover by glucopiercidin A / Soon Cheol Ahn; Bo Yeon Kim; Chan Sun Park; Hyun Sun Lee; Pan Ghill Suh; Sung Ho Ryu; Hyune Mo Rho; J S Rhee; Tae Ick Mheen; Jong Seog Ahn , 1995 ...