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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have provided evidence for axon-to-myelin transfer of intact lipids and lipid precursors for reutilization by myelin enzymes. Several of the lipid constituents of myelin showed significant contralateral/ipsilateral ratios of incorporated radioactivity, indicative of axonal origin, whereas proteins and certain other lipids did not participate in this transfer-reutilization process. The present study will examine the labeling of myelin phosphoinositides by this pathway. Both 32PO4 and [3H]inositol were injected monocularly into 7-9-wk-old rabbits and myelin was isolated 7 or 21 days later from pooled optic tracts and superior colliculi. In total lipids 32P counts of the isolated myelin samples showed significant contralateral/ipsilateral ratios as well as increasing magnitude of contralateral-ipsilateral differences during the time interval. Thin-layer chromatographic isolation of the myelin phosphoinositides revealed significant 32P-labeling of these species, with PIP and PIP2 showing time-related increases. This resembled the labeling pattern of the major phospholipids from rabbit optic system myelin in a previous study and suggested incorporation of axon-derived phosphate by myelin-associated enzymes. The 32P label in PI, on the other hand, remained constant between 7 and 21 days, suggesting transfer of intact lipid. This was supported by the labeling pattern with [3H]inositol, which also showed no increase over time for PI. These results suggest axon-myelin transfer of intact PI followed by myelin-localized incorporation of axon-derived phosphate groups into PIP and PIP2. The general topic of axon-myelin transfer of phospholipids and phospholipid precursors is reviewed.
Mol Neurobiol
PMID:Axon-myelin transfer of phospholipids and phospholipid precursors. Labeling of myelin phosphoinositides through axonal transport. 128 30

The X-ray structure of the nucleosome core particle was solved at 7 A resolution using the method of multiple isomorphous replacement based on two isomorphous derivatives, each containing a different multiple heavy-atom compound. The preparation of these heavy-atom compounds and their application to this macromolecular structure determination are described. The first of these reagents, TAMM (tetrakis(acetoxymercuri)methane), was solubilized by the addition of an excess of glycylglycine and, when added to crystals of the nucleosome core particle, produced a derivative with a single major site. Despite the large mass of 206,000 daltons per asymmetric unit, the position of the TAMM molecule was found in these crystals using the difference Patterson technique. This compound was sufficiently electron-dense to produce a unique solution, whereas the mono-mercurial, methylmercury nitrate had been inadequate. The second reagent, PIP (di-mu-iodobis(ethylenediamine)diplatinum(II) nitrate), is freely soluble in aqueous solution and, on addition to the crystals, labelled the histone proteins at several sites. The locations of the PIP groups were determined from difference Fourier and Patterson maps. The X-ray structure and solution characterization of this compound are reported. These multiple heavy-atom compounds appear to be generally applicable to X-ray structure determination, and are particularly useful in conjunction with crystals having asymmetric units of large volume but lacking non-crystallographic symmetry elements.
J Mol Biol 1987 Apr 20
PMID:Multiple heavy-atom reagents for macromolecular X-ray structure determination. Application to the nucleosome core particle. 365 3

Incubation of the insect gland with [3H]inositol results in the incorporation of label into both phosphatidylinositol (PI) and the two polyphosphoinositides (PIP and PIP2). Upon stimulation with 5-HT the initial water-soluble metabolites released are inositol trisphosphate and inositol bisphosphate with no change in the level of inositol monophosphate, suggesting that the primary lipid substrate used by the receptor is one of the polyphosphoinositides (most likely PIP2) rather than PI. This conclusion was substantiated by showing that 5-HT was not able to release inositol or inositol monophosphate when the levels of the two polyphosphoinositides were reduced by lowering the level of ATP. The rate of breakdown of the polyphosphoinositides, as measured by the appearance of inositol phosphates, occurred with no apparent lag whereas the onset of the calcium-dependent change in transepithelial potential had a latency of approximately 1 sec. It is concluded that the primary action of 5-HT is to stimulate the hydrolysis of PIP2 into diacylglycerol and inositol trisphosphate. The latter may function as a second messenger to mobilize the calcium responsible for initiating some of the ionic events responsible for fluid secretion.
Mol Cell Endocrinol 1984 Jun
PMID:Relationship of polyphosphoinositide metabolism to the hormonal activation of the inset salivary gland by 5-hydroxytryptamine. 608 23

The purpose of these studies was to examine the effects of hypoxia on alpha 1-adrenergic receptor (alpha 1AR) mediated phosphatidylinositol (PI) turnover in cultured neonatal rat cardiac myocytes. Cells were pre-labeled with [3H]-inositol and incubated for 1 h in either normoxia or hypoxia. Phenylephrine, an alpha 1AR agonist, was added at various time intervals (0-60 min) before termination of the incubation. There was a time-dependent release of radioactivity from the lipid fraction to the aqueous fraction with alpha 1AR stimulation. alpha 1AR-mediated PI turnover was biphasic in normoxic cells and monophasic in hypoxic cells. Using ion-exchange chromatography, radioactivity in the inositol trisphosphate (IP3) peak was increased with acute phenylephrine stimulation (5 min) in the normoxic cells, while inositol phosphate (IP) and inositol bisphosphate (IP2) were increased with chronic stimulation (60 min). After 5 min of alpha 1AR stimulation, hypoxia did not alter total aqueous radioactivity when compared to normoxia, but there was a significant increase in IP2. However, there was decreased PI turnover in chronically stimulated (30-60 min) hypoxic cells when compared to normoxic cells. Hypoxia had no effect on radioactivity in the IP3 fraction with either 0, 5, or 60 min of alpha 1AR stimulation, but there was a significant increase in [1,4,5]-IP3 in hypoxic cells with 30 s alpha 1AR stimulation. With hypoxia, there was no difference in radioactivity in the phosphatidylinositols with either 0 or 5 min stimulation when compared to normoxia. However, after 60 min of alpha 1AR stimulation, hypoxia resulted in increased PI and PIP, when compared to normoxic cells, but PIP2 radioactivity was unchanged. There was no effect of pertussis toxin on either the acute or chronic phase of PI turnover, negating involvement of Gi or G(o). These data suggest that alpha 1AR stimulation in neonatal rat cardiac myocytes is biphasic, and that hypoxia produces a slower monophasic response during extended alpha 1-agonist exposure as would be found with ischemia.
J Mol Cell Cardiol 1993 Oct
PMID:Alterations in alpha 1-adrenergic receptor-mediated phosphatidylinositol turnover in hypoxic cardiac myocytes. 826 53

Terminal deoxynucleotidyl Transferase (TdT) play an essential role in the immune system differentiation. KM-3 cells are lymphoblastoid cells expressing the TdT and when induced to differentiate by phorbol ester (PMA) they loose this enzyme. Therefore, because of the suggested involvement of polyphosphoinositide in controlling the nuclear events it has been analyzed the phosphorylation of nuclear polyphosphoinositides during KM-3 differentiation. When the differentiated state is reached the phosphorylation level of PIP2 increases in isolated nuclei and this is accompanied by a concomitant decrease of PIP and PA, hinting at a correlation between polyphosphoinositide metabolism and TdT expression.
Biochem Mol Biol Int 1993 Apr
PMID:Phorbol ester induces changes in the synthesis of nuclear polyphosphoinositides and expression of terminal deoxynucleotidil transferase (TdT) in nuclei of KM-3 cells. 839 17

In this paper we describe the molecular characterization of hrpB, the largest operon in the Xanthomonas campestris pv. vesicatoria hrp cluster. The hrpB region encompasses 6 kb and encodes eight putative proteins, seven of which were expressed in Escherichia coli. The HrpB3 protein is the only one carrying a signal peptide sequence at the N-terminus and is a putative lipoprotein localized in the outer membrane of X. campestris pv. vesicatoria. The HrpB4 and HrpB8 proteins contain one and five putative transmembrane domains, respectively, and are most likely associated with the inner membrane. The HrpB3, HrpB5, HrpB6, and HrpB8 proteins show sequence similarity to putative components of different type III protein secretion pathways in bacteria. Examples include Hrp proteins from other plant pathogens, YscJ, YscN, YscL, and YscT of Yersinia spp., and MxiJ, Spa47, adn Spa29 of Shigella flexneri. The transcription start site and the hrpB promoter was identified. The minimal hrpB promoter region of 90 bp contains a novel sequence motif, the PIP-box, which might play a role in transcription activation of the hrpB operon and possibly other plant-induced genes of X. campestris pv. vesicatoria.
Mol Plant Microbe Interact
PMID:Sequence and expression analysis of the hrpB pathogenicity operon of Xanthomonas campestris pv. vesicatoria which encodes eight proteins with similarity to components of the Hrp, Ysc, Spa, and Fli secretion systems. 866 94

The human prolactin-inducible protein/gross cystic disease fluid protein-15 (PIP/GCDFP-15) gene is expressed in more than 90% of human breast cancer biopsies but not in the normal mammary gland. However, it is expressed in several normal human apocrine glands such as the lacrimal and salivary glands. In human breast cancer cell lines, the gene is regulated by a number of hormones including androgen and prolactin. It is not known whether gene expression in normal tissues is under similar hormonal control. To understand the mechanisms by which hormone- and tissue-specific expression of the human PIP/GCDFP-15 gene are regulated in vivo, we generated transgenic mice using a 13.7 kb genomic DNA fragment containing the entire 7 kb human gene, together with 2.9 kilobases of 5' and 3.8 kilobases of 3' flanking sequences. The human PIP/GCDFP-15 transgene was found to be expressed in both the lacrimal and salivary glands but was not expressed in the mammary glands of transgenic mice. This tissue-specific pattern of the transgene expression in the mouse was very similar to that of the endogenous human PIP/GCDFP-15 gene, and to the endogenous mouse,gene. In the mouse salivary glands, the transgene expression was highest in the parotid, considerably less in the submaxillary (submandibular) and absent in the sublingual glands. In the mouse lacrimal gland, as in the human breast cancer cell lines, the human PIP/GCDFP-15 transgene was also up-regulated by androgen. These studies demonstrate that the human gene with its 6.3 kb flanking sequences is able to confer gene expression in vivo in a tissue-specific and hormone-responsive manner.
J Mol Endocrinol 1998 Oct
PMID:Analysis of tissue- and hormone-specific regulation of the human prolactin-inducible protein/gross cystic disease fluid protein-15 gene in transgenic mice. 980 65

Phosphatidylinositol-4,5-bisphosphate plays a pivotal role in the regulation of cell proliferation and survival, cytoskeletal reorganization, and membrane trafficking. However, little is known about the temporal and spatial regulation of its synthesis. Higher eukaryotic cells have the potential to use two distinct pathways for the generation of phosphatidylinositol-4,5-bisphosphate. These pathways require two classes of phosphatidylinositol phosphate kinases, termed type I and type II PIP kinases. While highly related by sequence, these kinases localize to different subcellular compartments, phosphorylate distinct substrates, and are functionally nonredundant. Here, we show that a 20- to 25-amino acid loop spanning the catalytic site, termed the activation loop, determines both enzymatic specificity and subcellular targeting of PIP kinases. Therefore, the activation loop controls signaling specificity and PIP kinase function at multiple levels.
Mol Cell 2000 Jan
PMID:The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity. 1067 64

The inositol 1,4,5-trisphosphate receptor (InsP(3)R) is activated by InsP(3) binding to amino-terminal ligand binding domain (InsP(3)R-N). Recently we reported functional coupling of phosphatidylinositol (4, 5)-bisphosphate (PIP(2)) to the InsP(3)R. Specific binding of PIP(2) to InsP(3)R-N domain was postulated as a part of the InsP(3)R-PIP(2) functional coupling model. Here we utilized bacterially expressed and purified InsP(3)R-N domain to characterize its binding specificity for InsP(3), Adenophostin A (AdA) and the water-soluble PIP(2) analog dioctanoyl-(4,5)PIP(2) (ShPIP(2)). Obtained data led us to conclude that specific InsP(3), AdA, and ShPIP(2) binding sites are located within the InsP(3)R-N domain, that the extra receptor binding element responsible for enhanced binding of AdA is an integral part of the InsP(3)R-N domain, that ShPIP(2) is able to displace InsP(3) from the InsP(3)R-N, but InsP(3) or AdA is unable to completely displace ShPIP(2). These results support the InsP(3)R-PIP(2) functional coupling model and provide novel insights into InsP(3)R ligand specificity.
Mol Cell Biol Res Commun 2000 Mar
PMID:Association of the inositol (1,4,5)-trisphosphate receptor ligand binding site with phosphatidylinositol (4,5)-bisphosphate and adenophostin A. 1086 Aug 63

We previously demonstrated that TSH activates phospholipase D (PLD) in Fischer rat thyroid line (FRTL)-5 cells. To date, two types of mammalian phosphatidylcholine-specific PLD cDNAs, designated as PLD-1 and PLD-2, have been cloned. The present study determined the PLD isoform composition in FRTL-5 thyroid cells and which isoform is regulated by TSH. PLD-1 is activated by small molecular weight G-proteins, such as ADP-ribosylation factor (ARF) and RhoA family members, while PLD-2 is relatively independent of such stimuli. We established the presence of PLD-1 and PLD-2 by Western blot analysis and compared PLD activity in cytosol, membranes and combined fractions in the presence and absence of GTPgammaS. The membrane fraction showed very little activity in the absence of GTPgammaS, but this activity increased approximately 5-fold (P<0.05, ANOVA) in the presence of GTPgammaS. Maximal PLD activity was seen with the combination of membrane plus cytosolic fractions (which contained ARF and RhoA) where the addition of GTPgammaS increased PLD activity approximately 8-fold (P<0.05, ANOVA). To determine the relative activities of PLD-1 and PLD-2 in FRTL-5 thyroid cells, cell-free PLD assays were performed in the presence of GTPgammaS or GDPbetaS with varying concentrations of phosphatidylinositol 4,5-bisphosphate (PIP(2)). PLD-2 contributed only approximately 19% of the total amount of PLD activity in the membranes and PLD-1 was the predominant PLD isoform. TSH stimulated PLD-1 activity by up to 2. 3-fold over control values (P<0.01, ANOVA). To establish the dependence of PLD-1 on small molecular weight G-proteins, the translocations of ARF and RhoA to the membrane fractions was determined after stimulation by TSH. Both ARF and RhoA were maximally translocated to the membrane fraction after 10 min incubation with 100 microU/ml TSH by approximately 1.7- and 2.3-fold over control values, respectively (P<0.02 and P<0.03, ANOVA). It is concluded that TSH stimulates PLD-1 activity in FRTL-5 thyroid cells and this is accompanied by the translocation of ARF and RhoA to the membrane fraction.
Mol Cell Endocrinol 2000 Sep 25
PMID:The characterization of phospholipase D in FRTL-5 thyroid cells. 1100 May 25


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