DBC2, a candidate for a tumor suppressor gene involved in breast cancer.
AuthorsHamaguchi Masaaki; Meth Jennifer L; von Klitzing Christine; Wei Wen; Esposito Diane; Rodgers Linda; Walsh Tom; Welcsh Piri; King Mary-Claire; Wigler Michael H;
JournalProc Natl Acad Sci U S A
PubMed ID12370419
A previously uncharacterized gene, DBC2 (deleted in breast cancer), was cloned from a homozygously deleted region at human chromosome 8p21. DBC2 contains a highly conserved RAS domain and two putative protein interacting domains. Our analyses indicate that DBC2 is the best candidate tumor suppressor gene from this region. It lies ... More
Neuropilin-1 binds vascular endothelial growth factor 165, placenta growth factor-2, and heparin via its b1b2 domain.
'Neuroplin-1 (NRP1), a receptor for vascular endothelial growth factor (VEGF) family members, has three distinct extracellular domains, a1a2, b1b2, and c. To determine the VEGF(165) and placenta growth factor 2 (PlGF-2)-binding sites of NRP1, recombinant NRP1 domains were expressed in mammalian cells as Myc-tagged, soluble proteins, and used in co-precipitation ... More
TID1, a human homolog of the Drosophila tumor suppressor l(2)tid, encodes two mitochondrial modulators of apoptosis with opposing functions.
AuthorsSyken J, De-Medina T, Munger K
JournalProc Natl Acad Sci U S A
PubMed ID10411904
'Mitochondria have emerged as central regulators of apoptosis. Here, we show that TID1, a human homolog of the Drosophila tumor suppressor lethal (2) tumorous imaginal discs, l(2)tid, encodes two mitochondrial matrix proteins, designated hTid-1(L) and hTid-1(S). These splice variants are both highly conserved members of the DnaJ family of proteins, ... More
Human mitochondrial 5'-deoxyribonucleotidase. Overproduction in cultured cells and functional aspects.
'Deoxynucleoside triphosphates (dNTPs) used for mitochondrial DNA replication are mainly formed by phosphorylation of deoxynucleosides imported into mitochondria from the cytosol. We earlier obtained evidence for a mitochondrial 5''-nucleotidase (dNT2) with a pronounced specificity for dUMP and dTMP and suggested that the enzyme protects mitochondrial DNA replication from excess dTTP. ... More
Cellular response to oncogenic ras involves induction of the Cdk4 and Cdk6 inhibitor p15(INK4b).
AuthorsMalumbres M, Perez De Castro I, Hernandez MI, Jimenez M, Corral T, Pellicer A
JournalMol Cell Biol
PubMed ID10733595
'The cell cycle inhibitor p15(INK4b) is frequently inactivated by homozygous deletion together with p16(INK4a) and p19(ARF) in some types of tumors. Although the tumor suppressor capability of p15(INK4b) is still questioned, it has been found to be specifically inactivated by hypermethylation in hematopoietic malignancies in the absence of p16(INK4a) alterations. ... More
Presenilin 1 mutations activate gamma 42-secretase but reciprocally inhibit epsilon-secretase cleavage of amyloid precursor protein (APP) and S3-cleavage of notch.
Authors Chen Fusheng; Gu YongJun; Hasegawa Hiroshi; Ruan Xueying; Arawaka Shigeki; Fraser Paul; Westaway David; Mount Howard; St George-Hyslop Peter;
JournalJ Biol Chem
PubMed ID12119298
'The presenilin 1 (PS1) and presenilin 2 (PS2) proteins are necessary for proteolytic cleavage of the amyloid precursor protein (APP) within its transmembrane domain. One of these cleavage events (termed gamma-secretase) generates the C-terminal end of the Abeta-peptide by proteolysis near residue 710 or 712 of APP(770). Another event (termed ... More
Mitogen-activated protein kinases and activator protein 1 are required for proliferation and cardiomyocyte differentiation of P19 embryonal carcinoma cells.
Authors Eriksson Minna; Leppä Sirpa;
JournalJ Biol Chem
PubMed ID11884386
'Mitogen-activated protein kinases (MAPKs) have been implicated as regulators of differentiation. The biological effect of MAPK signaling in the nucleus is achieved by signal-responsive transcription factors. Here we have investigated MAPK signaling and activation of AP-1 transcription factors in P19 embryonal carcinoma cells undergoing cardiomyocyte differentiation. We show that aggregation ... More
Enhanced production and oligomerization of the 42-residue amyloid beta- protein by Chinese hamster ovary cells stably expressing mutant presenilins.
AuthorsXia W, Zhang J, Kholodenko D, Citron M, Podlisny MB, Teplow DB, Haass C, Seubert P, Koo EH, Selkoe DJ
JournalJ Biol Chem
PubMed ID9065468
'Mutations in the presenilin 1 (PS1) and presenilin 2 (PS2) genes cause the most common and aggressive form of early onset familial Alzheimer''s disease. To elucidate their pathogenic mechanism, wild-type (wt) or mutant (M146L, C410Y) PS1 and wt or mutant (M239V) PS2 genes were stably transfected into Chinese hamster ovary ... More
Protein kinase C-alpha activity modulates transepithelial permeability and cell junctions in the LLC-PK1 epithelial cell line.
'Modulation of protein kinase C (PKC) by 12-O-tetradecanoylphorbol-13- acetate (TPA) disrupts the cell-cell junctions of the epithelial cell line LLC-PK1. To examine the role of specific PKC isoforms in this process we have created modified LLC-PK1 subclones that express wild- type and dominant negative versions of PKC-alpha under control of ... More
Mutational switch of an IL-6 response to an interferon-gamma-like response.
Authors Costa-Pereira Ana P; Tininini Silvia; Strobl Birgit; Alonzi Tonino; Schlaak Joerg F; Is'harc Hayaatun; Gesualdo Ida; Newman Sally J; Kerr Ian M; Poli Valeria;
JournalProc Natl Acad Sci U S A
PubMed ID12060750
'Signaling through Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) is central to the responses to the majority of cytokines and some growth factors, including the interferons (IFNs) and the IL-6 family of cytokines. The biological responses to stimulation through the widely distributed IL-6 and IFN-gamma receptors ... More
Two distinct proteins are associated with tetrameric acetylcholinesterase on the cell surface.
'In mammalian brain, acetylcholinesterase (AChE) exists mostly as a tetramer of 70-kDa catalytic subunits that are linked through disulfide bonds to a hydrophobic subunit P of approximately 20 kDa. To characterize P, we reduced the disulfide bonds in purified bovine brain AChE and sequenced tryptic fragments from bands in the ... More
Pattern of genes influenced by conditional expression of the transcription factors HNF6, HNF4alpha and HNF1beta in a pancreatic beta-cell line.
'Using the rat insulinoma cell line INS-1 we generated beta-cell clones that are most efficient for gene transfer, as they contain an FRT site for Flp recombinase-mediated, site-directed integration of a single copy transgene. Therefore, the gene-of-interest can be introduced by DNA transfection without the need to select individual cell ... More
Authors Stockand J D; Al-Baldawi N F; Al-Khalili O K; Worrell R T; Eaton D C;
JournalJ Biol Chem
PubMed ID9920939
'Aldosterone-induced Na+ reabsorption, in part, is regulated by a critical methyl esterification; however, the signal transduction pathway regulating this methylation remains unclear. The A6 cell line was used as a model epithelia to investigate regulation of aldosterone-induced Na+ transport by S-adenosyl-L-homocysteine hydrolase (SAHHase), the only enzyme in vertebrates known to ... More
Activation of orphan receptors by the hormone relaxin.
'Relaxin is a hormone important for the growth and remodeling of reproductive and other tissues during pregnancy. Although binding sites for relaxin are widely distributed, the nature of its receptor has been elusive. Here, we demonstrate that two orphan heterotrimeric guanine nucleotide binding protein (G protein)-coupled receptors, LGR7 and LGR8, ... More
Hepatitis C virus subgenomic replicons in the human embryonic kidney 293 cell line.
AuthorsAli S, Pellerin C, Lamarre D, Kukolj G,
JournalJ Virol
PubMed ID14671129
'Hepatitis C virus (HCV) infects liver cells and its replication in other cells is incompletely defined. Human hepatoma Huh-7 cells harboring subgenomic HCV replicons were used in somatic cell fusion experiments with human embryonic kidney 293 cells as a means of examining the permissiveness of 293 cells for HCV subgenomic ... More
Protein tyrosine phosphatase-PEST regulates focal adhesion disassembly, migration, and cytokinesis in fibroblasts.
AuthorsAngers-Loustau A, Cote JF, Charest A, Dowbenko D, Spencer S, Lasky LA, Tremblay ML
JournalJ Cell Biol
PubMed ID10085298
'In this article, we show that, in transfected COS-1 cells, protein tyrosine phosphatase (PTP)-PEST translocates to the membrane periphery following stimulation by the extracellular matrix protein fibronectin. When plated on fibronectin, PTP-PEST (-/-) fibroblasts display a strong defect in motility. 3 h after plating on fibronectin, the number and size ... More
Transcellular transport of organic anions across a double-transfected Madin-Darby canine kidney II cell monolayer expressing both human organic anion-transporting polypeptide (OATP2/SLC21A6) and Multidrug resistance-associated protein 2 (MRP2/ABCC2).
'Human organic anion transporting polypeptide 2 (OATP2/SLC21A6) and multidrug resistance-associated protein 2 (MRP2/ABCC2) play important roles in the vectorial transport of organic anions across hepatocytes. In the present study, we have established a double-transfected Madin-Darby canine kidney (MDCK II) cell monolayer, which expresses both OATP2 and MRP2 on basal and ... More
TRPM4 Is a Ca(2+)-Activated Nonselective Cation Channel Mediating Cell Membrane Depolarization.
Authors Launay Pierre; Fleig Andrea; Perraud Anne Laure; Scharenberg Andrew M; Penner Reinhold; Kinet Jean Pierre;
JournalCell
PubMed ID12015988
'Calcium-activated nonselective (CAN) cation channels are expressed in various excitable and nonexcitable cells supporting important cellular responses such as neuronal bursting activity, fluid secretion, and cardiac rhythmicity. We have cloned and characterized a second form of TRPM4, TRPM4b, a member of the TRP channel family, as a molecular candidate of ... More
Intracellular localization, function, and dysfunction of the peroxisome-targeting signal type 2 receptor, Pex7p, in mammalian cells.
'We previously isolated and characterized a Chinese hamster ovary (CHO) cell mutant, ZPG207, that is defective in import of proteins carrying a peroxisome-targeting signal type 2 (PTS2) nonapeptide. Herein we have cloned Chinese hamster (Cl) PEX7 encoding the PTS2 receptor. ClPex7p consists of 318 amino acids, shorter than human Pex7p ... More
The Role of Constant Region Carbohydrate in the Assembly and Secretion of Human IgD and IgA1.
Authors Gala Francoise A; Morrison Sherie L;
JournalJ Biol Chem
PubMed ID12023968
'Immunoglobulins are glycoproteins, containing N- linked carbohydrates in the heavy chain constant regions of all isotypes and O-linked carbohydrates in the hinge regions of human IgA1 and IgD. A previous study showed that IgD synthesized in the presence of tunicamycin and lacking the three N-linked glycans on the heavy chain ... More
Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema.
AuthorsKarkkainen MJ, Ferrell RE, Lawrence EC, Kimak MA, Levinson KL, McTigue MA, Alitalo K, Finegold DN
JournalNature Genetics
PubMed ID10835628
Primary lymphoedema is a rare, autosomal dominant disorder that leads to a disabling and disfiguring swelling of the extremities and, when untreated, tends to worsen with time. Here we link primary human lymphoedema to the FLT4 locus, encoding vascular endothelial growth factor receptor-3 (VEGFR-3), in several families. All disease-associated alleles ... More
Modulation of postendocytic sorting of G protein-coupled receptors.
AuthorsWhistler JL, Enquist J, Marley A, Fong J, Gladher F, Tsuruda P, Murray SR, Von Zastrow M,
JournalScience
PubMed ID12142540
Recycling of the mu opioid receptor to the plasma membrane after endocytosis promotes rapid resensitization of signal transduction, whereas targeting of the delta opioid receptor (DOR) to lysosomes causes proteolytic down-regulation. We identified a protein that binds preferentially to the cytoplasmic tail of the DOR as a candidate heterotrimeric GTP-binding ... More
Role of BAX in the apoptotic response to anticancer agents.
AuthorsZhang L, Yu J, Park BH, Kinzler KW, Vogelstein B
JournalScience
PubMed ID11062132
To assess the role of BAX in drug-induced apoptosis in human colorectal cancer cells, we generated cells that lack functional BAX genes. Such cells were partially resistant to the apoptotic effects of the chemotherapeutic agent 5-fluorouracil, but apoptosis was not abolished. In contrast, the absence of BAX completely abolished ... More
Retention of mutant low density lipoprotein receptor in ER leads to ER stress.
Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the gene encoding the low density lipoprotein receptor (LDLR). More than 50% of these mutations lead to receptor proteins that are completely or partly retained in the endoplasmic reticulum (ER). The mechanisms involved in the intracellular processing and ... More
Human immunodeficiency virus type 1 Vpr-dependent cell cycle arrest through a mitogen-activated protein kinase signal transduction pathway.
AuthorsYoshizuka N, Yoshizuka-Chadani Y, Krishnan V, Zeichner SL,
JournalJ Virol
PubMed ID16103188
The human immunodeficiency virus type 1 (HIV-1) Vpr protein has important functions in advancing HIV pathogenesis via several effects on the host cell. Vpr mediates nuclear import of the preintegration complex, induces host cell apoptosis, and inhibits cell cycle progression at G(2), which increases HIV gene expression. Some of Vpr's ... More
Endocytic function, glycosaminoglycan specificity, and antibody sensitivity of the recombinant human 190-kDa hyaluronan receptor for endocytosis (HARE).
AuthorsHarris EN, Weigel JA, Weigel PH,
JournalJ Biol Chem
PubMed ID15208308
The human hyaluronan receptor for endocytosis (hHARE) mediates the endocytic clearance of hyaluronan (HA) and chondroitin sulfate from lymph fluid and blood. Two hHARE isoforms (190 and 315 kDa) are present in sinusoidal endothelial cells of liver, spleen, and lymph nodes (Zhou, B., McGary, C. T., Weigel, J. A., Saxena, ... More
Mevalonate kinase is a cytosolic enzyme in humans.
In the past decade several reports have appeared which suggest that peroxisomes play a central role in isoprenoid/cholesterol biosynthesis. These suggestions were based primarily on the reported finding of several of the enzymes of the presqualene segment of the biosynthetic pathway in peroxisomes. More recently, however, conflicting results have been ... More
Identification of a novel dexamethasone-sensitive RNA-destabilizing region on rat monocyte chemoattractant protein 1 mRNA.
AuthorsPoon M, Liu B, Taubman MB
JournalMol Cell Biol
PubMed ID10490587
Glucocorticoids are potent anti-inflammatory agents widely used in the treatment of human disease. We have previously shown that the inflammatory cytokine monocyte chemoattractant protein 1 (MCP-1) is regulated posttranscriptionally by glucocorticoids in arterial smooth muscle cells (SMC). To elucidate the mechanism mediating this effect, in vitro-transcribed radiolabeled MCP-1 mRNA was ... More
Astrocyte-specific Expression of the {alpha}1-Antichymotrypsin and Glial Fibrillary Acidic Protein Genes Requires Activator Protein-1.
AuthorsGopalan SM, Wilczynska KM, Konik BS, Bryan L, Kordula T,
JournalJ Biol Chem
PubMed ID16303762
An amyloid-associated serine proteinase inhibitor (serpin), alpha(1)-antichymotrypsin (ACT), is encoded by a gene located within the distal serpin subcluster on human chromosome 14q32.1. The expression of these distal serpin genes is determined by tissue-specific chromatin structures that allow their ubiquitous expression in hepatocytes; however, their expression is limited to a ... More
A set of independent selectable markers for transfection of the human malaria parasite Plasmodium falciparum.
AuthorsMamoun CB, Gluzman IY, Goyard S, Beverley SM, Goldberg DE
JournalProc Natl Acad Sci U S A
PubMed ID10411941
Genomic information is rapidly accumulating for the human malaria pathogen, Plasmodium falciparum. Our ability to perform genetic manipulations to understand Plasmodium gene function is limited. Dihydrofolate reductase is the only selectable marker presently available for transfection of P. falciparum. Additional markers are needed for complementation and for expression of mutated ... More
Hematopoietic activity of a stromal cell transmembrane protein containing epidermal growth factor-like repeat motifs.
AuthorsMoore KA, Pytowski B, Witte L, Hicklin D, Lemischka IR
JournalProc Natl Acad Sci U S A
PubMed ID9108096
Primitive hematopoietic stem cells are closely associated with discrete in vivo microenvironments. These niches are thought to provide the molecular signals that mediate stem cell differentiation and self- renewal. We have dissected the fetal liver microenvironment into distinct cellular components by establishing an extensive panel of stromal cell lines. One ... More
Post-translational modifications of recombinant P-selectin glycoprotein ligand-1 required for binding to P- and E-selectin.
P-selectin glycoprotein ligand-1 (PSGL-1) is a mucin-like ligand for P- and E-selectin on human leukocytes. PSGL-1 requires sialylated, fucosylated O-linked glycans and tyrosine sulfate to bind P-selectin. Less is known about the determinants that PSGL-1 requires to bind E- selectin. To further define the modifications required for PSGL-1 to bind ... More
The C terminus of Ku80 activates the DNA-dependent protein kinase catalytic subunit.
AuthorsSingleton BK, Torres-Arzayus MI, Rottinghaus ST, Taccioli GE, Jeggo PA
JournalMol Cell Biol
PubMed ID10207052
Ku is a heterodimeric protein with double-stranded DNA end-binding activity that operates in the process of nonhomologous end joining. Ku is thought to target the DNA-dependent protein kinase (DNA-PK) complex to the DNA and, when DNA bound, can interact and activate the DNA-PK catalytic subunit (DNA-PKcs). We have carried out ... More
Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury.
AuthorsDore S, Takahashi M, Ferris CD, Hester LD, Guastella D, Snyder SH
JournalProc Natl Acad Sci U S A
PubMed ID10051662
Heme oxygenase (HO) catalyzes the conversion of heme to carbon monoxide, iron, and biliverdin, which is immediately reduced to bilirubin (BR). Two HO active isozymes exist: HO1, an inducible heat shock protein, and HO2, which is constitutive and highly concentrated in neurons. We demonstrate a neuroprotective role for BR formed ... More
Fusion of green fluorescent protein with the Zeocin-resistance marker allows visual screening and drug selection of transfected eukaryotic cells.
AuthorsBennett RP, Cox CA, Hoeffler JP
JournalAnal Biochem
PubMed ID9526661
Green fluorescent protein (GFP) and the Zeocin-resistance gene Sh ble (ZeoR) were fused together to generate a bifunctional protein for the identification and selection of transfected mammalian cells. Expression of this hybrid selectable marker, GFP-ZeoR, was visually detected and conferred Zeocin resistance in prokaryotes and eukaryotes. This selectable marker provides ... More
Requirement for either a host- or pectin-induced pectate lyase for infection of pisum sativum by nectriahematococca.
AuthorsRogers LM, Kim YK, Guo W, Gonzalez-Candelas L, Li D, Kolattukudy PE
JournalProc Natl Acad Sci U S A
PubMed ID10931947
Fungal pathogens usually have multiple genes that encode extracellular hydrolytic enzymes that may degrade the physical barriers in their hosts during the invasion process. Nectria hematococca, a plant pathogen, has two inducible pectate lyase (PL) genes (pel) encoding PL that can help degrade the carbohydrate barrier in the host. pelA ... More
Efficient intracellular assembly of papillomaviral vectors.
Although the papillomavirus structural proteins, L1 and L2, can spontaneously coassemble to form virus-like particles, currently available methods for production of L1/L2 particles capable of transducing reporter plasmids into mammalian cells are technically demanding and relatively low-yield. In this report, we describe a simple 293 cell transfection method for efficient ... More
Growth inhibition by keratinocyte growth factor receptor of human salivary adenocarcinoma cells through induction of differentiation and apoptosis.
Authors Zhang Y; Wang H; Toratani S; Sato J D; Kan M; McKeehan W L; Okamoto T;
JournalProc Natl Acad Sci U S A
PubMed ID11562460
We have reported that normal human salivary gland-derived epithelial cells exclusively express keratinocyte growth factor receptor (KGFR). In the process of malignant transformation of human salivary gland tumors, KGFR gene expression disappeared concomitantly with the de novo expression of the fibroblast growth factor receptor 1 (FGFR1) and FGFR4 genes. In ... More
Authors Greenfield Jeffrey P; Leung Lawrence W; Cai Dongming; Kaasik Krista; Gross Rachel S; Rodriguez-Boulan Enrique; Greengard Paul; Xu Huaxi;
JournalJ Biol Chem
PubMed ID11823458
Estrogen reduces the risk of Alzheimer's disease in post-menopausal women, beta-amyloid (Abeta) burden in animal models of Alzheimer's disease, and secretion of Abeta from neuronal cultures. The biological basis for these effects remains unknown. Here, utilizing cell-free systems derived from both neuroblastoma cells and primary neurons, we demonstrate that 17beta-estradiol ... More
Differential activation of p53 by the various adducts of mitomycin C.
Authors Abbas Tarek; Olivier Magali; Lopez Jaqueline; Houser Sandra; Xiao Gu; Kumar Gopinatha Suresh; Tomasz Maria; Bargonetti Jill;
JournalJ Biol Chem
PubMed ID12183457
Mitomycin C (MC) is a cytotoxic chemotherapeutic agent that causes DNA damage in the form of DNA cross-links as well as a variety of DNA monoadducts and is known to induce p53. The various DNA adducts formed upon treatment of mouse mammary tumor cells with MC as well as 10-decarbamoyl ... More
Identification in Drosophila melanogaster of the invertebrate G protein-coupled FMRFamide receptor.
We here describe the cloning and characterization of the functionally active Drosophila melanogaster (Drm) FMRFamide receptor, which we designated as DrmFMRFa-R. The full-length ORF of a D. melanogaster orphan receptor, CG 2114 (Berkeley Drosophila Genome Project), was cloned from genomic DNA. This receptor is distantly related to mammalian thyroid-stimulating hormone-releasing ... More
Distinct kinetics for binding of the CD46 and SLAM receptors to overlapping sites in the measles virus hemagglutinin protein.
Measles virus (MV) is a human pathogen using two distinct cell surface receptors for entry into host cells. We present here a comparative analysis for binding of the MV receptors CD46 and SLAM to the measles virus hemagglutinin protein (MVH, Edmonston strain). Soluble monomeric and dimeric MVH variants were prepared ... More
Assembly limits the pharmacological complexity of ATP-sensitive potassium channels.
Authors Giblin Jonathan P; Cui Yi; Clapp Lucie H; Tinker Andrew;
JournalJ Biol Chem
PubMed ID11825905
ATP-sensitive potassium channels (K(ATP) channels) are formed from an octameric complex of an inwardly rectifying K(+) channel (Kir6.1, Kir6.2) and a sulfonylurea receptor (SUR1, SUR2A, and SUR2B). In this study we have attempted to address the question of whether SUR heteromultimers can form using a combination of biochemical and electrophysiological ... More
Regulation of angiotensin II-induced G protein signaling by phosducin-like protein.
Authors McLaughlin Joseph N; Thulin Craig D; Bray Steven M; Martin Mickey M; Elton Terry S; Willardson Barry M;
JournalJ Biol Chem
PubMed ID12107186
Phosducin-like protein (PhLP) is a broadly expressed member of the phosducin (Pd) family of G protein betagamma subunit (Gbetagamma)-binding proteins. Though PhLP has been shown to bind Gbetagamma in vitro, little is known about its physiological function. In the present study, the effect of PhLP on angiotensin II (Ang II) ... More
Up-regulation of plasma membrane-associated ganglioside sialidase (Neu3) in human colon cancer and its involvement in apoptosis suppression.
Human plasma membrane-associated sialidase (Neu3) is unique in specifically hydrolyzing gangliosides, thought to participate in cell differentiation and transmembrane signaling, thereby playing crucial roles in the regulation of cell surface functions. We have discovered levels of mRNA for this sialidase to be increased in restricted cases of human colon cancer ... More
Bcl-2 family member Bfl-1/A1 sequesters truncated bid to inhibit is collaboration with pro-apoptotic Bak or Bax.
Authors Werner Arlette B; de Vries Evert; Tait Stephen W G; Bontjer Ilja; Borst Jannie;
JournalJ Biol Chem
PubMed ID11929871
Following caspase-8 mediated cleavage, a carboxyl-terminal fragment of the BH3 domain-only Bcl-2 family member Bid transmits the apoptotic signal from death receptors to mitochondria. In a screen for possible regulators of Bid, we defined Bfl-1/A1 as a potent Bid interacting protein. Bfl-1 is an anti-apoptotic Bcl-2 family member, whose preferential ... More
Engineered herpes simplex virus 1 is dependent on IL13Ralpha 2 receptor for cell entry and independent of glycoprotein D receptor interaction.
Authors Zhou Guoying; Ye Guo-Jie; Debinski Waldemar; Roizman Bernard;
JournalProc Natl Acad Sci U S A
PubMed ID12417744
In the first stage of engineering a herpes simplex virus (HSV)-1 that specifically targets human malignant glioma cells, we constructed a recombinant virus designated R5111 in which we have ablated the binding sites for sulfated proteoglycans in glycoproteins B and C, replaced the amino-terminal 148 aa in glycoprotein C by ... More
Internalized group V secretory phospholipase A2 acts on the perinuclear membranes.
Authors Kim Young Jun; Kim Kwang Pyo; Rhee Hae Jin; Das Sudipto; Rafter John D; Oh Youn Sang; Cho Wonhwa;
JournalJ Biol Chem
PubMed ID11777916
Mammalian secretory phospholipases A(2) (sPLA(2)) have been implicated in cellular eicosanoid biosynthesis but the mechanism of their cellular action remains unknown. To elucidate the spatiotemporal dynamics of sPLA(2) mobilization and determine the site of its lipolytic action, we performed time-lapse confocal microscopic imaging of fluorescently labeled sPLA(2) acting on human ... More
Authors Belcheva M M; Szùcs M; Wang D; Sadee W; Coscia C J;
JournalJ Biol Chem
PubMed ID11457825
Phosphorylation of the MAPK isoform ERK by G protein-coupled receptors involves multiple signaling pathways. One of these pathways entails growth factor receptor transactivation followed by ERK activation. This study demonstrates that a similar signaling pathway is used by the mu-opioid receptor (MOR) expressed in HEK293 cells and involves calmodulin (CaM). ... More
CrkL is recruited through its SH2 domain to the erythropoietin receptor and plays a role in Lyn-mediated receptor signaling.
Authors Arai A; Kanda E; Nosaka Y; Miyasaka N; Miura O;
JournalJ Biol Chem
PubMed ID11443118
The erythropoietin (Epo) receptor transduces its signals by activating physically associated tyrosine kinases, mainly Jak2 and Lyn, and thereby inducing tyrosine phosphorylation of various substrates including the Epo receptor (EpoR) itself. We previously demonstrated that, in Epo-stimulated cells, an adapter protein, CrkL, becomes tyrosine-phosphorylated, physically associates with Shc, SHP-2, and ... More
Uncoupling protein 2 plays an important role in nitric oxide production of lipopolysaccharide-stimulated macrophages.
The expression of uncoupling protein 2 (UCP2) was reduced in macrophages after stimulation with lipopolysaccharide (LPS). The physiological consequence and the regulatory mechanisms of the UCP2 down-regulation by LPS were investigated in a macrophage cell line, RAW264 cells. UCP2 overexpression in RAW264 cells transfected with eukaryotic expression vector containing ucp2 ... More
Inducible expression of a constitutively active mutant of mitogen-activated protein kinase kinase 7 specifically activates c-JUN NH2-terminal protein kinase, alters expression of at least nine genes, and inhibits cell proliferation.
Authors Wolter Sabine; Mushinski J Frederic; Saboori Ali M; Resch Klaus; Kracht Michael;
JournalJ Biol Chem
PubMed ID11714698
MKK7 is a recently discovered mitogen-activated protein kinase (MAPK) kinase that is unique in that it specifically activates only the c-JUN NH(2)-terminal protein kinase (JNK) family of enzymes. Very little is known about the biological role of MKK7. We generated inducible cell lines from the human embryonal kidney carcinoma cell ... More
Two rhodopsins mediate phototaxis to low- and high-intensity light in Chlamydomonas reinhardtii.
Authors Sineshchekov Oleg A; Jung Kwang-Hwan; Spudich John L;
JournalProc Natl Acad Sci U S A
PubMed ID12084907
We demonstrate that two rhodopsins, identified from cDNA sequences, function as low- and high-light-intensity phototaxis receptors in the eukaryotic alga Chlamydomonas reinhardtii. Each of the receptors consists of an approximately 300-residue seven-transmembrane helix domain with a retinal-binding pocket homologous to that of archaeal rhodopsins, followed by approximately 400 residues of ... More
Punctin, a novel ADAMTS-like molecule, ADAMTSL-1, in extracellular matrix.
Authors Hirohata Satoshi; Wang Lauren W; Miyagi Masaru; Yan Lin; Seldin Michael F; Keene Douglas R; Crabb John W; Apte Suneel S;
JournalJ Biol Chem
PubMed ID11805097
Punctin (ADAMTSL-1) is a secreted molecule resembling members of the ADAMTS family of proteases. Punctin lacks the pro-metalloprotease and the disintegrin-like domain typical of this family but contains other ADAMTS domains in precise order including four thrombospondin type I repeats. Punctin is the product of a distinct gene on human ... More
Membrane targeting of C2 domains of phospholipase C-delta isoforms.
Authors Ananthanarayanan Bharath; Das Sudipto; Rhee Sue Goo; Murray Diana; Cho Wonhwa;
JournalJ Biol Chem
PubMed ID11706040
The C2 domain is a Ca(2+)-dependent membrane-targeting module found in many cellular proteins involved in signal transduction or membrane trafficking. To understand the mechanisms by which the C2 domain mediates the membrane targeting of PLC-delta isoforms, we measured the in vitro membrane binding of the C2 domains of PLC-delta1, -delta3, ... More
Yeast Expression and NMR Analysis of the Extracellular Domain of Muscle Nicotinic Acetylcholine Receptor alpha Subunit.
Authors Yao Yun; Wang Junmei; Viroonchatapan Nitnara; Samson Avraham; Chill Jordan; Rothe Elizabeth; Anglister Jacob; Wang Zuo-Zhong;
JournalJ Biol Chem
PubMed ID11812776
The alpha subunit of the nicotinic acetylcholine receptor (AChR) from Torpedo electric organ and mammalian muscle contains high affinity binding sites for alpha-bungarotoxin and for autoimmune antibodies in sera of patients with myasthenia gravis. To obtain sufficient materials for structural studies of the receptor-ligand complexes, we have expressed part of ... More
The minor subunit splice variants, H2b and H2c, of the human asialoglycoprotein receptor are present with the major subunit H1 in different hetero-oligomeric receptor complexes.
Authors Yik Jasper H N; Saxena Amit; Weigel Paul H;
JournalJ Biol Chem
PubMed ID11943787
The hepatic asialoglycoprotein receptor (ASGP-R) is an endocytic receptor that mediates the internalization of desialylated glycoproteins and their delivery to lysosomes. The human ASGP-R is a hetero-oligomeric complex composed of H1 and H2 subunits. There are three naturally occurring H2 splice variants, designated H2a, H2b, and H2c, although the expression ... More
Murine Colonic Organoid Culture System and Downstream Assay Applications.
AuthorsFan YY, Davidson LA, Chapkin RS
JournalMethods Mol Biol
PubMed ID27539462
'Colonic organoids, three-dimensional colonic crypts grown in vitro that show realistic microanatomy, have many potential applications for studying physiology, developmental biology, and pathophysiology of intestinal diseases including inflammatory bowel disease and colorectal cancer. Here, we describe detailed protocols for mouse colonic crypt isolation, organoid culture, and downstream applications. Specific culture ... More
Genetic Engineering of Human Pluripotent Stem Cells Using PiggyBac Transposon System.
AuthorsPark MA, Jung HS, Slukvin I
JournalCurr Protoc Stem Cell Biol
PubMed ID30281932
'Human pluripotent stem cells (hPSCs) emerged as an important tool to investigate human development and disease. These studies often require genetically engineering hPSCs to stably express a transgene, which remains functional in various hPSC progeny. PiggyBac transposon is a highly effective and technically simple vector system with large cargo space ... More
Genome-scale activation screen identifies a lncRNA locus regulating a gene neighbourhood.
'Mammalian genomes contain thousands of loci that transcribe long noncoding RNAs (lncRNAs), some of which are known to carry out critical roles in diverse cellular processes through a variety of mechanisms. Although some lncRNA loci encode RNAs that act non-locally (in trans), there is emerging evidence that many lncRNA loci ... More
?-Aminobutyric Acid Type A (GABAA) Receptor Subunits Play a Direct Structural Role in Synaptic Contact Formation via Their N-terminal Extracellular Domains.
AuthorsBrown LE, Nicholson MW, Arama JE, Mercer A, Thomson AM, Jovanovic JN
JournalJ Biol Chem
PubMed ID27129275
The establishment of cell-cell contacts between presynaptic GABAergic neurons and their postsynaptic targets initiates the process of GABAergic synapse formation. GABAA receptors (GABAARs), the main postsynaptic receptors for GABA, have been recently demonstrated to act as synaptogenic proteins that can single-handedly induce the formation and functional maturation of inhibitory synapses. ... More
Orphan Adhesion GPCR GPR64/ADGRG2 Is Overexpressed in Parathyroid Tumors and Attenuates Calcium-Sensing Receptor-Mediated Signaling.
AuthorsBalenga N, Azimzadeh P, Hogue JA, Staats PN, Shi Y, Koh J, Dressman H, Olson JA
JournalJ Bone Miner Res
PubMed ID27760455
Abnormal feedback of serum calcium to parathyroid hormone (PTH) secretion is the hallmark of primary hyperparathyroidism (PHPT). Although the molecular pathogenesis of parathyroid neoplasia in PHPT has been linked to abnormal expression of genes involved in cell growth (e.g., cyclin D1, retinoblastoma, and ß-catenin), the molecular basis of abnormal calcium ... More
Diazepam-induced loss of inhibitory synapses mediated by PLCd/ Ca
AuthorsNicholson MW, Sweeney A, Pekle E, Alam S, Ali AB, Duchen M, Jovanovic JN
JournalMol Psychiatry
PubMed ID29904150
Benzodiazepines facilitate the inhibitory actions of GABA by binding to ?-aminobutyric acid type A receptors (GABA
Autophagy Monitoring Assay II: Imaging Autophagy Induction in LLC-PK1 Cells Using GFP-LC3 Protein Fusion Construct.
AuthorsAdiseshaiah PP, Skoczen SL, Rodriguez JC, Potter TM, Kota K, Stern ST
JournalMethods Mol Biol
PubMed ID29039105
Autophagy is a catabolic process involved in the degradation and recycling of long-lived proteins and damaged organelles for maintenance of cellular homeostasis, and it has also been proposed as a type II cell death pathway. The cytoplasmic components targeted for catabolism are enclosed in a double-membrane autophagosome that merges with ... More
Inhibition of
AuthorsQiu JF, Li X, Cui WZ, Liu XF, Tao H, Yang K, Dai TM, Sima YH, Xu SQ
JournalFront Physiol
PubMed ID31130878
Circadian clock system disorders can lead to uncontrolled cell proliferation, but the molecular mechanism remains unknown. We used a
Endogenous oligodendroglial alpha-synuclein and TPPP/p25a orchestrate alpha-synuclein pathology in experimental multiple system atrophy models.
AuthorsMavroeidi P, Arvanitaki F, Karakitsou AK, Vetsi M, Kloukina I, Zweckstetter M, Giller K, Becker S, Sorrentino ZA, Giasson BI, Jensen PH, Stefanis L, Xilouri M
JournalActa Neuropathol
PubMed ID31011860
Multiple system atrophy (MSA) is characterized by the presence of distinctive glial cytoplasmic inclusions (GCIs) within oligodendrocytes that contain the neuronal protein alpha-synuclein (aSyn) and the oligodendroglia-specific phosphoprotein TPPP/p25a. However, the role of oligodendroglial aSyn and p25a in the formation of aSyn-rich GCIs remains unclear. To address this conundrum, we ... More