Abstract
We investigated the role of PI4P synthesis by the phosphatidylinositol 4-kinases, PI4KIIα and PI4KIIIβ, in epidermal growth factor (EGF)-stimulated phosphoinositide signaling and cell survival. In COS-7 cells, knockdown of either isozyme by RNA interference reduced basal levels of PI4P and PI(4,5)...
|
PMID: 21218173
PDF is available here.
Abstract
These results indicate that, for a proper MgATP up-regulation of NCX1, the enzyme responsible for PtdIns-4,5P2 synthesis must be (i) functionally competent and (ii) set in the NCX1 microenvironment closely associated to the exchanger. This kind of supramolecular structure is needed to optimize bindi...
|
PMID: 20933499
PDF is available here.
Abstract
We used a series of molecules known to inactivate various elements of the pathway. W-7 prevents CaM from interacting with other molecules. Neomycin isolates PIP(2) from PLC. U-73122 directly inactivates PLC. 2-APB blocks IP(3) receptors which would otherwise cause release of Ca(2+). Verapamil and Cd...
|
PMID: 20416320
PDF is available here.
Abstract
Pantothenate kinase (PanK) catalyzes the rate-controlling step in coenzyme A (CoA) biosynthesis. PanK3 is stringently regulated by acetyl-CoA and uses an ordered kinetic mechanism with ATP as the leading substrate. Biochemical analysis of site-directed mutants indicates that pantothenate binds in a...
|
PMID: 20797618
PDF is available here.
Abstract
We examined the subcellular localization of actin-associated proteins in wild-type, talin-deficient, and Wiskott-Aldrich Syndrome protein (WASP)-deficient NK cells bound to beads coated with the LFA-1 ligand intercellular adhesion molecule-1 (ICAM-1). In addition, we carried out coimmunoprecipitatio...
|
PMID: 20472831
PDF is available here.
Abstract
We determined the crystal structures of the archaeal tRNA(Sec).PSTK complex. PSTK consists of two independent linker-connected domains, the N-terminal catalytic domain (NTD) and the C-terminal domain (CTD). The D-arm.CTD binding occurs independently of and much more strongly than the acceptor-arm.NT...
|
PMID: 20705242
PDF is available here.
Abstract
The growing number of patients with type 2 diabetes stimulates the development of new antidiabetic drugs. New targets are addressed, as SGLT2 in the kidney or enzymes of glucose metabolism in the liver which might help to lower glucose levels and to overcome insulin resistance. The forthcoming years...
|
PMID: 21189647
PDF is available here.
Abstract
We investigated the role of S1P-metabolizing enzymes in modulating cellular responses to influenza virus infection. Overexpression of S1P lyase (SPL), which induces the degradation of S1P, interfered with the amplification of infectious influenza virus. Accordingly, SPL-overexpressing cells were muc...
|
PMID: 20519401
PDF is available here.
Abstract
We show here that sphingosine and 14-3-3 interact directly in the control of cell death. The binding of sphingosine to 14-3-3 proteins renders them phosphorylatable at the dimer interface, an event that abolishes the pro-survival signalling of 14-3-3. Sphingosine kinase 1 reduces availability of sph...
|
PMID: 20403428
PDF is available here.
Abstract
We report the kinetic mechanism and structure of the aminoglycoside phosphotransferase 2''-IVa (APH(2'')-IVa), an enzyme responsible for resistance to aminoglycoside antibiotics in clinical enterococcal and staphylococcal isolates. The enzyme operates via a Bi-Bi sequential mechanism in which the tw...
|
PMID: 20556826
PDF is available here.
Abstract
We demonstrate here a new concept termed "oncogene tolerance" whereby human EGF receptor 2 (HER2) increases sphingosine kinase 1 (SK1) expression in estrogen receptor-positive (ER(+)) MCF-7 HER2 cells and SK1, in turn, limits HER2 expression in a negative-feedback manner. The HER2-dependent increase...
|
PMID: 20516217
PDF is available here.
Abstract
WB analysis of NCAM may be instrumental in the identification of h-IBM/DMRV with atypical clinical or pathologic features....
|
PMID: 20644153
PDF is available here.
Abstract
We investigated the elemental composition of the fumble mutant, a model of the human disease. Surprisingly, flies carrying a fumble loss-of-function allele had a three-fold increase in total zinc levels per dry weight when compared to control strains, but no change in total iron, copper or manganese...
|
PMID: 20493851
PDF is available here.
Abstract
We demonstrate that the carboxyl-terminal catalytic domain, which contains the activation loop, is sufficient for plasma membrane localization of PpPIPK1, a type I/II B PIPK from the moss Physcomitrella patens. The importance of the carboxyl-terminal catalytic domain for plasma membrane localization...
|
PMID: 20427464
PDF is available here.
Sergio E Alvarez,
Kuzhuvelil B Harikumar,
Nitai C Hait,
Jeremy Allegood,
Graham M Strub,
Eugene Y Kim,
Michael Maceyka,
Hualiang Jiang,
Cheng Luo,
Tomasz Kordula,
Sheldon Milstien and
Sarah Spiegel
Abstract
We show that SphK1 and the production of S1P is necessary for lysine-63-linked polyubiquitination of RIP1, phosphorylation of IkappaB kinase and IkappaBalpha, and IkappaBalpha degradation, leading to NF-kappaB activation. These responses were mediated by intracellular S1P independently of its cell s...
|
PMID: 20577214
PDF is available here.
Abstract
Xylulokinase gene located on pCXS-RKTr was highly expressed in W5. The xylulokinase activity was 2. 87 times of the original strain. CONCLUSION: An integrative vector of industry strain Saccharomyces cerevisiae is successfully constructed and xylulokinase gene of Saccharomyces cerevisiae itself was...
|
PMID: 20687341
PDF is available here.
Abstract
We found that Nicotinamide riboside kinase 2b (Nrk2b) cell autonomously modulates the molecular composition of CMACs in vivo. Nrk2b is required for normal Laminin polymerization at the myotendinous junction (MTJ). In Nrk2b-deficient embryos, at MTJ loci where Laminin is not properly polymerized, mus...
|
PMID: 20566368
PDF is available here.
Abstract
We summarise the current small molecule inhibitors and related approaches for targeting the SKs, and their in vitro and in vivo efficacy. Furthermore, we highlight findings demonstrating the success of SK inhibition in cancer and a range of other disease models that promotes the continued interest i...
|
PMID: 20370685
PDF is available here.
Abstract
We report that the antiinflammatory activity of APC on macrophages is dependent on integrin CD11b/CD18, but not on endothelial protein C receptor (EPCR). We showed that CD11b/CD18 bound APC within specialized membrane microdomains/lipid rafts and facilitated APC cleavage and activation of protease-a...
|
PMID: 20458145
PDF is available here.
Abstract
We present the first structure for an InsP(5) 2-kinase in complex with both substrates and products. This enzyme presents a singular structural region for inositide binding that encompasses almost half of the protein. The key residues in substrate binding are identified, with Asp368 being responsibl...
|
PMID: 20453199
PDF is available here.
Abstract
We investigated the basis for these other phenotypes and found that they are dependent on the toxic biosynthetic intermediate homoserine. Moreover, homoserine is also toxic for Candida albicans thr1Delta mutants. Since increasing levels of threonine, but not other amino acids, overcome the homoserin...
|
PMID: 20305002
PDF is available here.
Abstract
We further explored the potential of threonine biosynthetic enzymes as antifungal drug targets by determining the survival in mice of Saccharomyces cerevisiae homoserine kinase (thr1Delta) and threonine synthase (thr4Delta) mutants. In striking contrast to aspartate kinase (hom3Delta) mutants, S. ce...
|
PMID: 20305003
PDF is available here.
Abstract
We cloned previously from common bean (PvP5CS). The predicted amino acid sequence of PvP5CS2 has an overall 93.2% identity GmP5CS (Glycine max L. P5CS). However, PvP5CS2 shows only 83.7% identity in amino acid sequence to PvP5CS, suggesting PvP5CS2 represents a homolog of the soybean P5CS gene. Abun...
|
PMID: 20143043
PDF is available here.
Abstract
We examined three enzymes, APH(3')-IIIa, APH(2'')-Ib, and MPH(2')-I, using a competitive assay that mimics in vivo nucleotide triphosphate (NTP) concentrations and usage by each enzyme. Downstream analysis of reaction products by high-performance liquid chromatography enabled the determination of pa...
|
PMID: 20231391
PDF is available here.
Abstract
We have shown that these [Ca(2+)](i) oscillations mediate oxLDL's ability to inhibit macrophage apoptosis in response to growth factor deprivation. However, the signal transduction pathways by which oxLDL induces [Ca(2+)](i) oscillations have not been elucidated. In this study, we show that these os...
|
PMID: 19965613
PDF is available here.
Abstract
The effects of two different sugars (glucose and xylose) on the expression levels and patterns of xylose reductase (xyl1), xylitol dehydrogenase (xyl2) and xylulokinase (xyl3) genes were analyzed using Pichia stipitis. A significant increase in mRNA levels of xyl1 was observed after 6 hours growth i...
|
PMID: 20519920
PDF is available here.
Abstract
We found a new regulator of tumor growth, phosphatidylinositol 4-kinase type IIalpha (PI4KIIalpha), the mechanism of which is involved in angiogenesis and hypoxia-inducible factor HIF-1alpha regulation. Results obtained from a human cancer tissue microarray showed that PI4KIIalpha protein expression...
|
PMID: 20154717
PDF is available here.
Abstract
We developed a new simple and reliable assay which is based on the quantification of Pi. This assay allowed us to determine the optimal pH, the apparent K(m) and V(m) of P5CS with regard to ATP and glutamate....
|
PMID: 20387057
PDF is available here.
Abstract
Hyperimmunoglobulinemia D and periodic fever syndrome, an autoinflammatory syndrome, is caused by mutations in the gene coding for mevalonate kinase. The disease is clinically characterized by recurrent attacks of fever accompanied by an array of inflammatory symptoms including lymphadenopathy, rash...
|
PMID: 20425018
PDF is available here.
Abstract
We studied the effects of NADK2 expression in rice by developing transgenic rice plants that constitutively expressed the Arabidopsis chloroplastic NADK gene (NK2 lines). NK2 lines showed enhanced activity of NADK and accumulation of the NADP(H) pool, while intermediates of NAD derivatives were unch...
|
PMID: 20154096
PDF is available here.
Abstract
Most of the phosphorus in the resting seed is stored inside protein storage vacuoles as PA (phytic acid; InsP(6)). The biosynthesis and accumulation of PA can be detected beginning from a few days after anthesis and seem to continue during seed development until maturation. The first step in PA bios...
|
PMID: 20298244
PDF is available here.
Bin Ma,
Kevin M Guckian,
Edward Yin-Shiang Lin,
Wen-Cherng Lee,
Daniel Scott,
Gnanasambandam Kumaravel,
Timothy L Macdonald,
Kevin R Lynch,
Cheryl Black,
Sowmya Chollate,
Kyungmin Hahm,
Gregg Hetu,
Ping Jin,
Yi Luo,
Ellen Rohde,
Anthony Rossomando,
Robert Scannevin,
Joy Wang and
Chunhua Yang
Abstract
Modifying FTY720, an immunosuppressant modulator, led to a new series of well phosphorylated tetralin analogs as potent S1P1 receptor agonists. The stereochemistry effect of tetralin ring was probed, and (-)-(R)-2-amino-2-((S)-6-octyl-1,2,3,4-tetrahydronaphthalen-2-yl)propan-1-ol was identified as a...
|
PMID: 20188554
PDF is available here.
Jun Shen,
Edward C Gilmore,
Christine A Marshall,
Mary Haddadin,
John J Reynolds,
Wafaa Eyaid,
Adria Bodell,
Brenda Barry,
Danielle Gleason,
Kathryn Allen,
Vijay S Ganesh,
Bernard S Chang,
Arthur Grix,
R Sean Hill,
Meral Topcu,
Keith W Caldecott,
A James Barkovich and
Christopher A Walsh
Abstract
We describe a previously unknown autosomal recessive disease characterized by microcephaly, early-onset, intractable seizures and developmental delay (denoted MCSZ). Using genome-wide linkage analysis in consanguineous families, we mapped the disease locus to chromosome 19q13.33 and identified multi...
|
PMID: 20118933
PDF is available here.
Abstract
We established a stable clone of PIP5KL1 overexpressing human cervical cancer HeLa cells. RT-PCR (reverse transcription-polymerase chain reaction) and Western immunoblot analysis were performed to testify the mRNA and protein levels of PIP5KL1 in HeLa cells. The effect of PIP5KL1 overexpression on i...
|
PMID: 19947914
PDF is available here.
Abstract
We discuss the role of neuronal Ca(2+)-sensor proteins in the regulation of PI4Kbeta and suggest that this regulation might impose a need for elevated Ca(2+) levels for a late step of vesicle assembly....
|
PMID: 20074055
PDF is available here.
Abstract
We measured and developed a quantitative description of these metabolic and protein interaction steps by perturbing the PIP(2) pool with a voltage-sensitive phosphatase (VSP). VSP can remove the 5-phosphate of PIP(2) with a time constant of tau <300 ms and fully inhibits KCNQ currents in a similar t...
|
PMID: 20100891
PDF is available here.
Abstract
I poison, camptothecin, but not the topoisomerase II poison, etoposide, in a manner similar to small interfering RNA against PNKP. A12B4C3 also inhibits the repair of DNA single and double strand breaks following exposure of cells to ionizing radiation, but does not inhibit two other key strand-brea...
|
PMID: 19940137
PDF is available here.
Abstract
The HPPCn was highly expressed in human HCC cells and secreted into culture medium (CM). FITC-labeled recombinant human protein (rhHPPCn) could specifically bind to its receptor on HepaG2 cells. Treatment with 400 ng/mL rhHPPCn dramatically increased the viability of HCC-derived cells from 48.1% and...
|
PMID: 20066738
PDF is available here.
Abstract
We study the effects of LQT1 mutations in putative PIP(2)-KCNQ1 interaction sites on regulation of IKs by PKA and GqPCR. The effect of the LQT1 mutations on IKs regulation was tested for mutations in conserved, positively charged amino acids, located in four distinct cytoplamic domains of the KCNQ1...
|
PMID: 19934648
PDF is available here.
Abstract
Using voltage-clamp technique, the role of tyrosine kinases and phosphatidylinositol kinases in the effect of oxidized glutathione (GSSG) and its pharmacological analogue, drug glutoxim, on Na+ transport in the frog Rana temporaria skin was investigated. It was shown for the first time that preincub...
|
PMID: 20540346
PDF is available here.
Christophe Lachaud,
Daniel Da Silva,
Valérie Cotelle,
Patrice Thuleau,
Tou Cheu Xiong,
Alain Jauneau,
Christian Brière,
Annick Graziana,
Yannick Bellec,
Jean-Denis Faure,
Raoul Ranjeva and
Christian Mazars
Abstract
We show that increase in tobacco BY-2 cells of the endogenous content of Long Chain Bases (LCBs) caused by external application of d-erythro-sphinganine (DHS) is followed by immediate dose-dependent elevations of cellular free calcium concentration within the first minute in the cytosol and 10min la...
|
PMID: 20022633
PDF is available here.
Abstract
Inositol 1,3,4,5,6-pentakisphosphate kinase (IP(5) 2-K) is an enzyme involved in inositol metabolism that synthesizes IP(6) (inositol 1,2,3,4,5,6-hexakisphosphate) from inositol 1,3,4,5,6-pentakisphosphate (IP(5)) and ATP. IP(6) is the major phosphorus reserve in plants, while in mammals it is invol...
|
PMID: 20057083
PDF is available here.
Abstract
We will highlight the variety of known physiological roles of NADP. In its reduced form (NADPH), this molecule represents a universal electron donor, not only to drive biosynthetic pathways. Perhaps even more importantly, NADPH is the unique provider of reducing equivalents to maintain or regenerate...
|
PMID: 20196923
PDF is available here.
Abstract
Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator with crucial roles in a wide variety of cellular functions across a broad range of organisms. Though a simple molecule in structure, S1P functions are complex. The formation of S1P is catalyzed by one of two sphingosine kinases that have dif...
|
PMID: 20919652
PDF is available here.
Abstract
The CERKL gene encodes for ceramide kinase-like, a novel protein of unknown function. CERKL mutations are associated with a severe retinal phenotype. The purpose of this work was to investigate alternative splicing, and the temporal and spatial expression pattern of CERKL in the mouse retina.
Revers...
|
PMID: 21151604
PDF is available here.
Abstract
We recently identified type II phosphatidylinositol 4-kinases alpha and beta (PI4KIIalpha and PI4KIIbeta) as being required for bacterial entry downstream of Met. In this work, we investigated whether tetraspanins CD9, CD63, and CD81, which figure among the few described molecular partners of PI4KII...
|
PMID: 19901060
PDF is available here.
Abstract
Our results confirm that transgenes on a replicating plasmid represent an excellent tool for effective protein production and suggest that efficient production of the Dm-dNK protein in tumor cells could be an attractive cancer therapy....
|
PMID: 20606317
PDF is available here.
Abstract
Collectively, our study demonstrates that S1P released via isoflurane-mediated SK1 stimulation produces direct anti-necrotic effects probably via S1P(1) receptor-mediated cytoprotective signaling (ERK/Akt phosphorylation and HSP70 induction) in HK-2 cells. Our findings may help to unravel the cellul...
|
PMID: 20234131
PDF is available here.
Abstract
We now study mRNA expression levels of the six ceramide synthase (CerS) genes in breast cancer tissue. CerS2 and CerS6 mRNA was significantly elevated in breast cancer tissue compared to paired normal tissue, with approximately half of the individuals showing elevated CerS2 and CerS6 mRNA. A signifi...
|
PMID: 19912991
PDF is available here.
Abstract
I CoaA. The cloned gene clearly complements the poor growth of the temperature-sensitive Escherichia coli CoaA mutant strain ts9, and the recombinant protein expressed in E. coli cells transfers phosphate to pantothenate at pH 5 and 55 degrees C. In contrast to E. coli CoaA, the P. torridus enzyme i...
|
PMID: 19854913
PDF is available here.
Abstract
The main symptoms of this patient were involuntary movements, dysarthria and progressive course. MRI scans showed hypointensity with a central region of hyperintensity in medial globus pallidus on T2 and T2-weighted fluid attenuated inversion recovery (FLAIR) images, i.e. "eye-of-the-tiger" sign. No...
|
PMID: 20193558
PDF is available here.
Abstract
Mitochondria is an intracellular double membrane-bound structure and it can provide energy for intracellular metabolism. The metabolism includes Krebs cycle, beta-oxidation and lipid synthesis. The density of mitochondria is different in various tissues dependent upon the demands of oxidative phosph...
|
PMID: 20329599
PDF is available here.
Abstract
We have now demonstrated for the first time that PTH stimulated BMP-2 mRNA expression via the mevalonate pathway and ROK in osteoblastic MC3T3-E1 cells.
Georg Thieme Verlag KG Stuttgart. New York....
|
PMID: 19672814
PDF is available here.
Abstract
We have studied the roles of LKB1, a conserved kinase implicated in the control of cell polarity and energy metabolism, in adult beta cells. LKB1-deficient beta cells show a dramatic increase in insulin secretion in vivo. Histologically, LKB1-deficient beta cells have striking alterations in the loc...
|
PMID: 19808022
PDF is available here.