Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion.
AuthorsFujino T, Asaba H, Kang MJ, Ikeda Y, Sone H, Takada S, Kim DH, Ioka RX, Ono M, Tomoyori H, Okubo M, Murase T, Kamataki A, Yamamoto J, Magoori K, Takahashi S, Miyamoto Y, Oishi H, Nose M, Okazaki M, Usui S, Imaizumi K, Yanagisawa M, Sakai J, Yamamoto TT,
JournalProc Natl Acad Sci U S A
PubMed ID12509515
A Wnt coreceptor low-density lipoprotein receptor-related protein 5 (LRP5) plays an essential role in bone accrual and eye development. Here, we show that LRP5 is also required for normal cholesterol and glucose metabolism. The production of mice lacking LRP5 revealed that LRP5 deficiency led to increased plasma cholesterol levels in ... More
Regulation of cortical dendrite development by Slit-Robo interactions.
Slit proteins have previously been shown to regulate axon guidance, branching, and neural migration. Here we report that, in addition to acting as a chemorepellant for cortical axons, Slit1 regulates dendritic development. Slit1 is expressed in the developing cortex, and exposure to Slit1 leads to increased dendritic growth and branching. ... More
Extracellular Export of Sphingosine Kinase-1 Enzyme. SPHINGOSINE 1-PHOSPHATE GENERATION AND THE INDUCTION OF ANGIOGENIC VASCULAR MATURATION.
AuthorsAncellin Nicolas; Colmont Chantal; Su Joseph; Li Qin; Mittereder Nanette; Chae Sung-Suk; Stefansson Steingrimur; Liau Gene; Hla Timothy;
JournalJ Biol Chem
PubMed ID11741921
The enzyme sphingosine kinase (SK) catalyzes the formation of sphingosine 1-phosphate (S1P), a bioactive lipid that acts extracellularly on G protein-coupled receptors of the S1P(1)/EDG-1 subfamily. Although S1P is formed in the cytosol of various cells, S1P release is not understood and is controversial because this lipid mediator is also ... More
Different composite regulatory elements direct expression of the human alpha subunit gene to pituitary and placenta.
Authors Heckert L L; Schultz K; Nilson J H;
JournalJ Biol Chem
PubMed ID7592867
'To identify elements of the human alpha subunit gene necessary for cell-specific expression, we generated an array of block mutations spanning approximately 400 base pairs (bp) of promoter proximal region and examined them using transient transfection analysis in pituitary (alpha T3) and placental (BeWo) cell lines. Comparison of promoter activity ... More
ATF3 gene. Genomic organization, promoter, and regulation.
Authors Liang G; Wolfgang C D; Chen B P; Chen T H; Hai T;
JournalJ Biol Chem
PubMed ID8576171
'ATF3 gene, which encodes a member of the activating transcription factor/cAMP responsive element binding protein (ATF/CREB) family of transcription factors, is induced by many physiological stresses. As a step toward understanding the induction mechanisms, we isolated the human ATF3 gene and analyzed its genome organization and 5''-flanking region. We found ... More
Protein kinase B/Akt mediates cAMP- and cell swelling-stimulated Na+/taurocholate cotransport and Ntcp translocation.
Authors Webster Cynthia R L; Srinivasulu Usha; Ananthanarayanan Meenakshisundaram; Suchy Frederick J; Anwer M Sawkat;
JournalJ Biol Chem
PubMed ID12034724
'Cyclic AMP and cell swelling stimulate hepatic Na+/TC cotransport and Ntcp translocation via the phosphoinositide 3-kinase signaling pathway. To determine the downstream target of the phosphoinositide 3-kinase action, we examined the role of protein kinase B (PKB)/Akt using SB203580 in hepatocytes as well as by transfection with a dominant negative ... More
Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo.
'A major concern in cancer therapy is resistance of tumors such as glioblastoma to current treatment protocols. Here, we report that transfer of the gene encoding second mitochondria-derived activator of caspase (Smac) or Smac peptides sensitized various tumor cells in vitro and malignant glioma cells in vivo for apoptosis induced ... More
PAX6 gene is activated by the basic helix-loop-helix transcription factor NeuroD/BETA2.
AuthorsMarsich E, Vetere A, Di Piazza M, Tell G, Paoletti S,
JournalBiochem J
PubMed ID12962539
'PAX6 is a transcription factor that plays an important role during pancreas morphogenesis. The aim of this study is to identify the upstream activator(s) of the PAX6 gene possibly involved in the early stage of pancreas differentiation. Recently, individual elements regulating the PAX6 gene activity in the pancreas have been ... More
An Induced Ets Repressor Complex Regulates Growth Arrest during Terminal Macrophage Differentiation.
Authors Klappacher Günter W; Lunyak Victoria V; Sykes David B; Sawka-Verhelle Dominique; Sage Julien; Brard Gyan; Ngo Sally D; Gangadharan Denise; Jacks Tyler; Kamps Mark P; Rose David W; Rosenfeld Michael G; Glass Christopher K;
JournalCell
PubMed ID12007404
'Defining the molecular mechanisms that coordinately regulate proliferation and differentiation is a central issue in development. Here, we describe a mechanism in which induction of the Ets repressor METS/PE1 links terminal differentiation to cell cycle arrest. Using macrophages as a model, we provide evidence that METS/PE1 blocks Ras-dependent proliferation without ... More
Flavonoid inhibition of sodium-dependent vitamin C transporter 1 (SVCT1) and glucose transporter isoform 2 (GLUT2), intestinal transporters for vitamin C and Glucose.
Authors Song Jian; Kwon Oran; Chen Shenglin; Daruwala Rushad; Eck Peter; Park Jae B; Levine Mark;
JournalJ Biol Chem
PubMed ID11834736
'Vitamin C and flavonoids, polyphenols with uncertain function, are abundant in fruits and vegetables. We postulated that flavonoids have a novel regulatory action of delaying or inhibiting absorption of vitamin C and glucose, which are structurally similar. From six structural classes of flavonoids, at least 12 compounds were chosen for ... More
Livin, a novel inhibitor of apoptosis protein family member.
Authors Kasof G M; Gomes B C;
JournalJ Biol Chem
PubMed ID11024045
'A novel human inhibitor of apoptosis protein (IAP) family member termed Livin was identified, containing a single baculoviral IAP repeat (BIR) domain and a COOH-terminal RING finger domain. The mRNA for livin was not detectable by Northern blot in most normal adult tissues with the exception of the placenta, but ... More
Mutation of the cytoplasmic domain of the integrin beta 3 subunit. Differential effects on cell spreading, recruitment to adhesion plaques, endocytosis, and phagocytosis.
Authors Ylänne J; Huuskonen J; O'Toole T E; Ginsberg M H; Virtanen I; Gahmberg C G;
JournalJ Biol Chem
PubMed ID7721884
'The cytoplasmic domain of the beta subunit of the alpha IIb beta 3 integrin is required for cell spreading on fibrinogen. Here we report that deletion of six amino acids from the COOH terminus of the beta 3 (I757TYRGT) totally abolished cell spreading and formation of adhesion plaques, whereas retaining ... More
The tumor suppressor protein TSLC1 is involved in cell-cell adhesion.
'TSLC1 is a tumor suppressor gene encoding a member of the immunoglobulin (Ig) superfamily. The significant homology of its extracellular domain with those of other Ig superfamily cell adhesion molecules (IgCAMs) has raised the possibility that TSLC1 participates in cell-cell interactions. In this study, the physiological properties of TSLC1 were ... More
A region of human CD14 required for lipopolysaccharide binding.
Authors Viriyakosol S; Kirkland T N;
JournalJ Biol Chem
PubMed ID7529231
'CD14, a glycosylphosphatidylinositol-anchored protein on the surface of monocytes, macrophages, and polymorphonuclear leukocytes, is a receptor for lipopolysaccharide (LPS). CD14 binding of LPS is enhanced by serum proteins, especially lipopolysaccharide binding protein. The serum-dependent binding of LPS to CD14 stimulates macrophages to make cytokines, which can cause septic shock in ... More
Complexes of focal adhesion kinase (FAK) and Crk-associated substrate (p130(Cas)) are elevated in cytoskeleton-associated fractions following adhesion and Src transformation. Requirements for Src kinase activity and FAK proline-rich motifs.
AuthorsPolte TR, Hanks SK
JournalJ Biol Chem
PubMed ID9038154
'The focal adhesion kinase (FAK) and Crk-associated substrate, p130(Cas) (Cas), have been implicated in diverse signaling pathways including those mediated by integrins, G-protein-coupled receptors, tyrosine kinase receptors, and the v-src and v-crk oncogenes. The recent identification of a direct interaction between FAK and Cas prompted the examination of potential regulation ... More
Isolation and characterization of the 5'-upstream region of the human N-type calcium channel alpha1B subunit gene. Chromosomal localization and promoter analysis.
Authors Kim D S; Jung H H; Park S H; Chin H;
JournalJ Biol Chem
PubMed ID9030575
'omega-Conotoxin-sensitive N-type Ca2+ channels, unlike dihydropyridine-sensitive L-type channels, are exclusively expressed in nervous tissues. To understand the molecular basis for neuron-specific expression of the N-type channel, we have isolated genomic clones encoding the human alpha1B subunit gene, localized to the long arm of chromosome 9 (9q34) by fluorescence in situ ... More
Altered carbohydrate recognition specificity engineered into surfactant protein D reveals different binding mechanisms for phosphatidylinositol and glucosylceramide.
Authors Ogasawara Y; Voelker D R;
JournalJ Biol Chem
PubMed ID7782337
'Pulmonary surfactant protein D (SP-D) is a member of the collection subgroup of the C-type lectin superfamily that binds glycosylated lipids such as phosphatidylinositol (PI) and glucosylceramide (GlcCer). We have previously reported that the carbohydrate recognition domain of SP-D plays an essential role in lipid binding. However, it is unclear ... More
Interferons inhibit tumor necrosis factor-alpha-mediated matrix metalloproteinase-9 activation via interferon regulatory factor-1 binding competition with NF-kappa B.
'Enhanced expression of matrix metalloproteinase-9 (MMP-9) correlates with invasion during tumor progression. Interferons (IFNs) inhibit MMP-9 activation in response to tumor necrosis factor-alpha (TNF-alpha), and the latter activates the MMP-9 gene through NF-kappaB. Understanding the molecular basis for MMP-9 inhibition may provide tools to control cell invasion. The data reported ... More
The major calpain isozymes are long-lived proteins. Design of an antisense strategy for calpain depletion in cultured cells.
AuthorsZhang W, Lane RD, Mellgren RL
JournalJ Biol Chem
PubMed ID8702541
'Calpains are intracellular Ca2+-dependent proteases that are thought to participate in Ca2+-associated signal transduction pathways. It has been proposed that calpains are activated by an autoproteolytic mechanism. If this is true one would expect a relatively short half-life for calpain protein in cells. To test this hypothesis, WI-38 human diploid ... More
Use of a promoterless Renilla luciferase vector as an internal control plasmid for transient co-transfection assays of Ras-mediated transcription activation.
Authors Behre G; Smith L T; Tenen D G;
JournalBiotechniques
PubMed ID9894587
'not available'
p53 suppresses the c-Myb-induced activation of heat shock transcription factor 3.
'Expression of heat shock proteins (HSPs) is controlled by heat shock transcription factors (HSFs). Vertebrates express multiple HSFs whose activities may be regulated by distinct signals. HSF3 is specifically activated in unstressed proliferating cells by direct binding to the c-myb proto-oncogene product (c-Myb), which plays an important role in cellular ... More
Characterization of the SECIS binding protein 2 complex required for the co-translational insertion of selenocysteine in mammals.
AuthorsKinzy SA, Caban K, Copeland PR,
JournalNucleic Acids Res
PubMed ID16155186
'Selenocysteine is incorporated into at least 25 human proteins by a complex mechanism that is a unique modification of canonical translation elongation. Selenocysteine incorporation requires the concerted action of a kink-turn structural RNA (SECIS) element in the 3'' untranslated region of each selenoprotein mRNA, a selenocysteine-specific translation elongation factor (eEFSec) ... More
The human acid alpha-glucosidase gene is a novel target of the Notch-1/Hes-1 signaling pathway.
AuthorsYan B, Raben N, Plotz P.
JournalJ Biol Chem
PubMed ID12065598
'Acid alpha-glucosidase (GAA) is a lysosomal enzyme that degrades glycogen. A deficiency of GAA is responsible for a recessively inherited myopathy and cardiomyopathy, glycogenosis type II. Previously, we identified an intronic repressor element in the GAA gene and demonstrated that Hes-1, a basic helix-loop-helix factor, binds to a C class ... More
p38 kinase-dependent and -independent Inhibition of protein kinase C zeta and -alpha regulates nitric oxide-induced apoptosis and dedifferentiation of articular chondrocytes.
AuthorsKim SJ, Kim HG, Oh CD, Hwang SG, Song WK, Yoo YJ, Kang SS, Chun JS.
JournalJ Biol Chem
PubMed ID12048219
'In articular chondrocytes, nitric oxide (NO) production triggers dedifferentiation and apoptotic cell death that is regulated by the converse functions of two mitogen-activated protein kinase subtypes, extracellular signal-regulated kinase (ERK) and p38 kinase. Since protein kinase C (PKC) transduces signals that influence differentiation, survival, and apoptosis of various cell types, ... More
Regulation of gene expression by cGMP-dependent protein kinase. Transactivation of the c-fos promoter.
Authors Gudi T; Huvar I; Meinecke M; Lohmann S M; Boss G R; Pilz R B;
JournalJ Biol Chem
PubMed ID8617718
'The cAMP/cAMP-dependent protein kinase (A-kinase) and Ca2+/calmodulin-dependent protein kinase (Cam-kinase) signal transduction pathways are well known to regulate gene transcription, but this has not been demonstrated directly for the cGMP/cGMP-dependent protein kinase (G-kinase) signal transduction pathway. Here we report that transfection of G-kinase into G-kinase-deficient cells causes activation of the ... More
Interaction of ethanol with inducers of glucose-regulated stress proteins. Ethanol potentiates inducers of grp78 transcription.
Authors Hsieh K P; Wilke N; Harris A; Miles M F;
JournalJ Biol Chem
PubMed ID8576245
GRP78, a molecular chaperone expressed in the endoplasmic reticulum, is a
mom identifies a receptor for the Drosophila JAK/STAT signal transduction pathway and encodes a protein distantly related to the mammalian cytokine receptor family.
Authors Chen Hua-Wei; Chen Xiu; Oh Su-Wan; Marinissen Maria J; Gutkind J Silvio; Hou Steven X;
JournalGenes Dev
PubMed ID11825879
The JAK/STAT signal transduction pathway controls numerous events in Drosophila melanogaster development. Receptors for the pathway have yet to be identified. Here we have identified a Drosophila gene that shows embryonic mutant phenotypes identical to those in the hopscotch (hop)/JAK kinase and marelle (mrl)/Stat92e mutations. We named this gene master ... More
Evidence that the WNT-inducible growth arrest-specific gene 1 encodes an antagonist of sonic hedgehog signaling in the somite.
Authors Lee C S; Buttitta L; Fan C M;
JournalProc Natl Acad Sci U S A
PubMed ID11572986
The dorsal-ventral polarity of the somite is controlled by antagonistic signals from the dorsal neural tube/surface ectoderm, mediated by WNTs, and from the ventral notochord, mediated by sonic hedgehog (SHH). Each factor can act over a distance greater than a somite diameter in vitro, suggesting they must limit each other's ... More
Noninfectious virus-like particles produced by Moloney murine leukemia virus-based retrovirus packaging cells deficient in viral envelope become infectious in the presence of lipofection reagents.
AuthorsSharma S, Murai F, Miyanohara A, Friedmann T
JournalProc Natl Acad Sci U S A
PubMed ID9380714
Retrovirus packaging cell lines expressing the Moloney murine leukemia virus gag and pol genes but lacking virus envelope genes produce virus-like particles constitutively, whether or not they express a transcript from an integrated retroviral provirus. In the absence of a proviral transcript, the assembled particles contain processed gag and reverse ... More
Tumor suppressor p53 and its homologue p73alpha affect cell migration.
AuthorsSablina AA, Chumakov PM, Kopnin BP,
JournalJ Biol Chem
PubMed ID12750388
The p53 tumor suppressor plays a central role in the negative control of growth and survival of abnormal cells. Previously we demonstrated that in addition to these functions, p53 expression affects cell morphology and lamellar activity of the cell edge (Alexandrova, A., Ivanov, A., Chumakov, P. M., Kopnin, P. B., ... More
Adenovirus-mediated heme oxygenase-1 gene transfer into rabbit ocular tissues.
AuthorsAbraham NG, da Silva JL, Lavrovsky Y, Stoltz RA, Kappas A, Dunn MW, Schwartzman ML
JournalInvest Ophthalmol Vis Sci
PubMed ID7558713
PURPOSE. Heme oxygenase-1 (HO-1) is a stress protein induced up to 100-fold within a few hours after exposure to oxidative stress, and it has been shown to counteract oxidative injury induced by ultraviolet light or free radicals. The current study was undertaken to determine whether the HO-1 gene can be ... More
Expression cloning and characterization of a cDNA encoding a novel membrane protein required for the formation of O-acetylated ganglioside: a putative acetyl-CoA transporter.
AuthorsKanamori A, Nakayama J, Fukuda MN, Stallcup WB, Sasaki K, Fukuda M, Hirabayashi Y
JournalProc Natl Acad Sci U S A
PubMed ID9096318
By expression cloning using COS-1 cells stably transfected with GD3- synthase (COS-1/GD3+) as a recipient cell line, we have isolated a cDNA, termed AT-1, encoding a novel protein required for the formation of O-acetylated (Ac) gangliosides. The cDNA encodes a protein with multitransmembrane spanning domains with a leucine zipper motif. ... More
Transcriptional roles of nuclear factor kappa B and nuclear factor-interleukin-6 in the tumor necrosis factor alpha-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells.
AuthorsYamamoto K, Arakawa T, Ueda N, Yamamoto S
JournalJ Biol Chem
PubMed ID8537402
When a mouse osteoblastic cell line MC3T3-E1 was cultured in the presence of tumor necrosis factor alpha (TNF alpha), the release of prostaglandin E2 and the cyclooxygenase activity increased in a dose- and time-dependent manner. The increase of the enzyme activity was attributed mostly to the induction of cyclooxygenase-2 rather ... More
Overexpression of myotonic dystrophy kinase in BC3H1 cells induces the skeletal muscle phenotype.
AuthorsBush EW, Taft CS, Meixell GE, Perryman MB
JournalJ Biol Chem
PubMed ID8550617
Myotonic muscular dystrophy is an autosomal dominant defect that produces muscle wasting, myotonia, and cardiac conduction abnormalities. The myotonic dystrophy locus codes for a putative serine- threonine protein kinase of unknown function. We report that overexpression of human myotonic dystrophy protein kinase induces the expression of skeletal muscle-specific genes in ... More
Green fluorescent protein-based system for analysis of E-selectin- mediated adhesion.
Authorsel-Battari A, Zerfaoui M, Panicot L, Mas E, Prevot C, Lombardo D
JournalBiotechniques
PubMed ID10090997
Numerous cell-based or cell-free systems for study of selectin adhesion use radiolabeled tracers. However, in addition to handling problems associated with the use of radioisotopes, these assays have difficulty relating a number of counts to a number of adherent cells. Here, we describe an assay that uses the natural fluorescence ... More
Phosphorylation of critical serine residues in Gem separates cytoskeletal reorganization from down-regulation of calcium channel activity.
AuthorsWard Y, Spinelli B, Quon MJ, Chen H, Ikeda SR, Kelly K,
JournalMol Cell Biol
PubMed ID14701738
Gem is a small GTP-binding protein that has a ras-like core and extended chains at each terminus. The primary structure of Gem and other RGK family members (Rad, Rem, and Rem2) predicts a GTPase deficiency, leading to the question of how Gem functional activity is regulated. Two functions for Gem ... More
Retrovirus-derived vectors are overwhelmingly preferred over other methods for ex vivo gene therapy because they provide permanent integration of foreign genes into cellular DNA. In comparison, cationic lipids mediate efficent gene transfer, but expression is transient. When we combined cationic lipids with retrovirus particles we obtained a significant enhancement of ... 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
The neuronal growth-associated protein (GAP)-43 (neuromodulin, B-50, F1), which is concentrated in the growth cones of elongating axons during neuronal development and in nerve terminals in restricted regions of the adult nervous system, has been implicated in the release of neurotransmitter. To study the role of GAP-43 in evoked secretion, ... More
Polypyrimidine tract-binding proteins are cleaved by caspase-3 during apoptosis.
Authors Back Sung Hoon; Shin Sejeong; Jang Sung Key;
JournalJ Biol Chem
PubMed ID12004072
The polypyrimidine tract-binding protein (PTB), an RNA-binding protein, is required for efficient translation of some mRNAs containing internal ribosomal entry sites (IRESs). Here we provide evidence that the addition of apoptosis-inducing agents to cells results in the cleavage of PTB isoforms 1, 2, and 4 by caspase-3. This cleavage of ... More
A cDNA encoding the calcitonin gene-related peptide type 1 receptor.
Authors Aiyar N; Rand K; Elshourbagy N A; Zeng Z; Adamou J E; Bergsma D J; Li Y;
JournalJ Biol Chem
PubMed ID8626685
Calcitonin gene-related peptide (CGRP) is a neuropeptide with diverse biological effects including potent vasodilator activity. We report here the cloning of a complementary DNA (cDNA) encoding a human CGRP1 receptor, which shares significant peptide sequence homology with the human calcitonin receptor, a member of the G-protein-coupled receptor superfamily. Northern blot ... More
Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice.
Authors Lee Tzong-Shyuan; Chau Lee-Young;
JournalNat Med
PubMed ID11875494
The mechanisms underlying the action of the potent anti-inflammatory interleukin-10 (IL-10) are poorly understood. Here we show that, in murine macrophages, IL-10 induces expression of heme oxygenase-1 (HO-1), a stress-inducible protein with potential anti-inflammatory effect, via a p38 mitogen-activated protein kinase-dependent pathway. Inhibition of HO-1 protein synthesis or activity significantly ... More
Regulation of cellular oncosis by uncoupling protein 2.
Authors Mills Edward M; Xu Dong; Fergusson Maria M; Combs Christian A; Xu Yuhui; Finkel Toren;
JournalJ Biol Chem
PubMed ID12011039
Cell death can proceed through at least two distinct pathways. Apoptosis is an energy-dependent process characterized morphologically by cell shrinkage, whereas oncosis is a form of cell death induced by energy depletion and initially characterized by cell swelling. We demonstrate in HeLa cells but not in normal diploid fibroblasts that ... More
Apocytochrome c Blocks Caspase-9 Activation and Bax-induced Apoptosis.
Authors Martin Angel G; Fearnhead Howard O;
JournalJ Biol Chem
PubMed ID12393884
Complex networks of signaling pathways control the apoptotic response and, therefore, cell survival. However, these networks converge on a common machinery, of which the caspase cysteine proteases are key components. Diverse apoptotic stimuli release holocytochrome c from mitochondria, allowing holocytochrome c to bind apoptotic protease activating factor-1 (Apaf-1), which in ... More
The Epstein-Barr virus oncogene product, latent membrane protein 1, induces the downregulation of E-cadherin gene expression via activation of DNA methyltransferases.
The latent membrane protein (LMP1) of Epstein-Barr virus (EBV) is expressed in EBV-associated nasopharyngeal carcinoma, which is notoriously metastatic. Although it is established that LMP1 represses E-cadherin expression and enhances the invasive ability of carcinoma cells, the mechanism underlying this repression remains to be elucidated. In this study, we demonstrate ... More
Tumor-cell resistance to death receptor--induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax.
The importance of Bax for induction of tumor apoptosis through death receptors remains unclear. Here we show that Bax can be essential for death receptor--mediated apoptosis in cancer cells. Bax-deficient human colon carcinoma cells were resistant to death-receptor ligands, whereas Bax-expressing sister clones were sensitive. Bax was dispensable for apical ... More
Expression of transforming growth factor type III receptor in vascular endothelial cells increases their responsiveness to transforming growth factor beta 2.
Authors Sankar S; Mahooti-Brooks N; Centrella M; McCarthy T L; Madri J A;
JournalJ Biol Chem
PubMed ID7768960
Bovine aortic endothelial cells (BAECs) express both type I and type II receptors for transforming growth factor beta (TGF beta). These cells respond to TGF beta 1 but are relatively refractory to another isoform of TGF beta, termed TGF beta 2. TGF beta s are thought to signal through receptor ... More
Activation of BAD by therapeutic inhibition of epidermal growth factor receptor and transactivation by insulin-like growth factor receptor.
Authors Gilmore Andrew P; Valentijn Anthony J; Wang Pengbo; Ranger Ann M; Bundred Nigel; O'Hare Michael J; Wakeling Alan; Korsmeyer Stanley J; Streuli Charles H;
JournalJ Biol Chem
PubMed ID12011069
Novel cancer chemotherapeutics are required to induce apoptosis by activating pro-apoptotic proteins. Both epidermal growth factor (EGF) and insulin-like growth factor (IGF) provide potent survival stimuli in many epithelia, and activation of their receptors is commonly observed in solid human tumors. Here we demonstrate that blockade of the EGF receptor ... More
Ligand promotes intranuclear inclusions in a novel cell model of spinal and bulbar muscular atrophy.
Authors Walcott Jessica L; Merry Diane E;
JournalJ Biol Chem
PubMed ID12388541
Spinal and bulbar muscular atrophy (SBMA, Kennedy's disease) is one of a group of progressive neurodegenerative diseases resulting from a polyglutamine repeat expansion. In SBMA the polymorphic trinucleotide CAG repeat in exon 1 of the androgen receptor (AR) gene is increased, resulting in expansion of a polyglutamine tract. Patient autopsy ... More
Defective human Ether-Ã -go-go-related gene trafficking linked to an endoplasmic reticulum retention signal in the C terminus.
Authors Kupershmidt Sabina; Yang Tao; Chanthaphaychith Siprachanh; Wang Zhiqing; Towbin Jeffrey A; Roden Dan M;
JournalJ Biol Chem
PubMed ID12021266
Mutations in the human Ether-Ã -go-go-Related gene (HERG), encoding the protein underlying the cardiac K(+) current, I(Kr), cause chromosome 7-linked long QT syndrome (LQT2). In this study, we show that deletion of the C-terminal 147 amino acids (HERG(Delta147)) abolished I(Kr), whereas a larger, 159-amino acid deletion (HERG(Delta159)) identified in an ... More
Serum response factor cleavage by caspases 3 and 7 linked to apoptosis in human BJAB cells.
Authors Drewett V; Devitt A; Saxton J; Portman N; Greaney P; Cheong N E; Alnemri T F; Alnemri E; Shaw P E;
JournalJ Biol Chem
PubMed ID11387340
Apoptosis involves the cessation of cellular processes, the breakdown of intracellular organelles, and, finally, the nonphlogistic clearance of apoptotic cells from the body. Important for these events is a family of proteases, caspases, which are activated by a proteolytic cleavage cascade and drive apoptosis by targeting key proteins within the ... More
Improvement of gene transduction efficiency in T lymphocytes using retroviral vectors.
Authors Wu A G; Liu X; Mazumder A; Bellanti J A; Meehan K R;
JournalHum Gene Ther
PubMed ID10223731
Successful gene transfer into T lymphocytes would provide a useful therapeutic modality for the treatment of various diseases and a valuable way to study T cell functions. Currently, most protocols involving gene transfer into T lymphocytes utilize amphotropic retroviral vectors. However, transduction efficiency using these vectors is relatively low because ... More
Proteolytic processing of familial British dementia-associated BRI variants: evidence for enhanced intracellular accumulation of amyloidogenic peptides.
Authors Kim Seong-Hun; Creemers John W M; Chu Su; Thinakaran Gopal; Sisodia Sangram S;
JournalJ Biol Chem
PubMed ID11709554
Different mutations in the BRI(2) gene cause rare neurodegenerative conditions, termed familial British dementia (FBD) and familial Danish dementia (FDD). The mutant genes encode BRI-L and BRI-D, the precursors of fibrillogenic ABri and ADan peptides, respectively. We previously reported that furin processes both BRI-L and its wild type counterpart, BRI, ... More
Accelerated phagocytosis of amyloid-beta by mouse and human microglia overexpressing the macrophage colony-stimulating factor receptor.
AuthorsMitrasinovic OM, Murphy GM Jr.
JournalJ Biol Chem
PubMed ID12032144
Microglia surrounding A beta plaques in Alzheimer's disease and in the APPV717F transgenic mouse model of Alzheimer's disease have enhanced immunoreactivity for the macrophage colony-stimulating factor receptor (M-CSFR), encoded by the proto-oncogene c-fms. Increased expression of M-CSFR on cultured microglia results in proliferation and release of pro-inflammatory cytokines and expression ... More
The gene encoding the Acyl-CoA-binding protein is activated by peroxisome proliferator-activated receptor gamma through an intronic response element functionally conserved between humans and rodents.
The acyl-CoA-binding protein (ACBP) is a 10-kDa intracellular protein that specifically binds acyl-CoA esters with high affinity and is structurally and functionally conserved from yeast to mammals. In vitro studies indicate that ACBP may regulate the availability of acyl-CoA esters for various metabolic and regulatory purposes. The protein is particularly ... More
Molecular cloning and characterization of human nonsteroidal anti-inflammatory drug-activated gene promoter. Basal transcription is mediated by Sp1 and Sp3.
Authors Baek S J; Horowitz J M; Eling T E;
JournalJ Biol Chem
PubMed ID11445565
Nonsteroidal anti-inflammatory drug-activated gene (NAG-1) is known to be associated with anti-tumorigenic activity and belongs to the transforming growth factor-beta superfamily. In the present study, we cloned the promoter region (-3500 to +41) and investigated the transcriptional regulatory mechanisms of the basal expression of the human NAG-1 gene. Several potential ... More
ILPIP, a novel anti-apoptotic protein that enhances XIAP-mediated activation of JNK1 and protection against apoptosis.
AuthorsSanna MG, da Silva Correia J, Luo Y, Chuang B, Paulson LM, Nguyen B, Deveraux QL, Ulevitch RJ.
JournalJ Biol Chem
PubMed ID12048196
We have previously described a new aspect of the Inhibitor of Apoptosis (IAP) family of proteins anti-apoptotic activity that involves the TAK1/JNK1 signal transduction pathway (1,2). Our findings suggest the existence of a novel mechanism that regulates the anti-apoptotic activity of IAPs that is separate from caspase inhibition but instead ... More
Activation of Constitutive Nitric-oxide Synthase Activity Is an Early Signaling Event Induced by Ionizing Radiation.
Authors Leach J Kevin; Black Stephen M; Schmidt-Ullrich Rupert K; Mikkelsen Ross B;
JournalJ Biol Chem
PubMed ID11856735
Ionizing radiation at clinical dose levels activates both pro- and anti-proliferative signal transduction pathways, the balance of which determines cell fate. The initiating and amplifying mechanisms involved in the activation are poorly understood. We demonstrate that one mechanism involves stimulation of constitutive nitric-oxide synthase (NOS) activity. NOS activity of Chinese ... More
Proteolysis of chimeric beta-amyloid precursor proteins containing the Notch transmembrane domain yields amyloid beta-like peptides.
Authors Zhang Jimin; Ye Wenjuan; Wang Rong; Wolfe Michael S; Greenberg Barry D; Selkoe Dennis J;
JournalJ Biol Chem
PubMed ID11839734
gamma-Secretase is an unusual intramembranous protease that has been reported to cleave the beta-amyloid precursor protein (APP) near the middle of its transmembrane domain (TMD) but cleave Notch near the cytoplasmic end of its TMD. To ascertain whether the TMD sequence of the substrate determines where gamma-secretase cleaves and whether ... More
Dynamics of diacylglycerol kinase zeta translocation in living T-cells. Study of the structural domain requirements for translocation and activity.
AuthorsSantos T, Carrasco S, Jones DR, Merida I, Eguinoa A.
JournalJ Biol Chem
PubMed ID12015310
The diacylglycerol kinases (DGK) regulate diacylglycerol-based signals by phosphorylating this key lipid intermediate to phosphatidic acid. Here, we have investigated the spatial and temporal regulation of diacylglycerol kinase zeta (DGK zeta) in living Jurkat T-cells expressing a muscarinic type I receptor. Using real time confocal videomicroscopy, we show the rapid ... More
'Srcasm: a novel Src activating and signaling molecule.
Authors Seykora John T; Mei Lijuan; Dotto G Paolo; Stein Paul L;
JournalJ Biol Chem
PubMed ID11711534
The Src family tyrosine kinase, Fyn, can facilitate regulation of cell proliferation and differentiation. Mice with mutations in the fyn gene have defects in the brain, immune system, and epidermal differentiation. To identify molecules that may interact with Fyn in the epidermis, we performed a yeast two-hybrid interaction screen of ... More
Structure of the m4 cholinergic muscarinic receptor gene and its promoter.
Authors Wood I C; Roopra A; Harrington C; Buckley N J;
JournalJ Biol Chem
PubMed ID8537349
Cholinergic muscarinic receptor genes are members of the G-protein receptor gene superfamily. In this study we describe the structure of the gene and promoter of the rat m4 muscarinic receptor gene. A rat cosmid clone containing the coding region for the m4 gene and 25 kilobases of upstream sequence was ... More
Inositol lipid binding and membrane localization of isolated pleckstrin homology (PH) domains. Studies on the PH domains of phospholipase C delta 1 and p130.
The relationship between the ability of isolated pleckstrin homology (PH) domains to bind inositol lipids or soluble inositol phosphates in vitro and to localize to cellular membranes in live cells was examined by comparing the PH domains of phospholipase Cdelta(1) (PLCdelta(1)) and the recently cloned PLC-like protein p130 fused to ... More
Functional analysis of the human endothelial nitric oxide synthase promoter. Sp1 and GATA factors are necessary for basal transcription in endothelial cells.
Authors Zhang R; Min W; Sessa W C;
JournalJ Biol Chem
PubMed ID7541039
To gain insights into the mechanisms of endothelial nitric oxide synthase (eNOS) gene expression, we have cloned the eNOS promoter and fused it to a luciferase reporter gene to map regions of the promoter important for basal transcription in bovine aortic endothelial cells (BAEC). Transfection of BAEC with F1 luciferase ... More
Regulation of G Protein-linked Guanine Nucleotide Exchange Factors for Rho, PDZ-RhoGEF, and LARG by Tyrosine Phosphorylation. EVIDENCE OF A ROLE FOR FOCAL ADHESION KINASE.
A recently identified family of guanine nucleotide exchange factors for Rho that includes PDZ-RhoGEF, LARG, and p115RhoGEF exhibits a unique structural feature consisting in the presence of area of similarity to regulators of G protein signaling (RGS). This RGS-like (RGL) domain provides a structural motif by which heterotrimeric G protein ... More
Inhibition of neointimal formation after stent placement with adenovirus-mediated gene transfer of I kappa B alpha in the hypercholesterolemic rabbit model: initial results.
Authors Cejna Manfred; Breuss Johannes M; Bergmeister Helga; de Martin Rainer; Xu Zhongying; Grgurin Mario; Losert Udo; Plenk Hanns Jr; Binder Bernd R; Lammer Johannes;
JournalRadiology
PubMed ID12034938
PURPOSE: To evaluate the feasibility and efficacy of the local application of a replication-defective adenovirus construct for the expression of the antiinflammatory protein I kappa B alpha, inhibitor of nuclear factor kappa B (NF-kappa B), to reduce neointimal formation after stent placement. MATERIALS AND METHODS: Nitinol stents were implanted in ... More
The third intracellular domain of the platelet-activating factor receptor is a critical determinant in receptor coupling to phosphoinositide phospholipase C-activating G proteins. Studies using intracellular domain minigenes and receptor chimeras.
AuthorsCarlson S A; Chatterjee T K; Fisher R A;
JournalJ Biol Chem
PubMed ID8798508
Platelet activating factor (PAF) is a potent phospholipid mediator which elicits a diverse array of biological actions by interacting with G protein-coupled PAF receptors (PAFR). Binding of PAF to PAFRs leads to activation of G protein(s) that stimulate phosphoinositide phospholipase C and subsequent intracellular signaling responses. To identify the potential ... More
Cysteine string protein interacts with and modulates the maturation of the cystic fibrosis transmembrane conductance regulator.
Authors Zhang Hui; Peters Kathryn W; Sun Fei; Marino Christopher R; Lang Jochen; Burgoyne Robert D; Frizzell Raymond A;
JournalJ Biol Chem
PubMed ID12039948
The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride channel whose phosphorylation regulates both channel gating and its trafficking at the plasma membrane. Cysteine string proteins (Csps) are J-domain-containing, membrane-associated proteins that have been functionally implicated in regulated exocytosis. Therefore, we evaluated the possibility that Csp is involved ... More
Generation of the mu opioid receptor (MOR-1) protein by three new splice variants of the Oprm gene.
Authors Pan Y X; Xu J; Mahurter L; Bolan E; Xu M; Pasternak G W;
JournalProc Natl Acad Sci U S A
PubMed ID11717463
Using 5' RACE, we have isolated four additional exons of the mu opioid receptor gene (Oprm), resulting in a gene spanning over 250 kb. The four new exons are contained within eight additional splice variants containing exon 11 at the 5' terminus. Exon 11, which is under the control of ... More
Focal adhesion kinase is involved in mechanosensing during fibroblast migration.
Authors Wang H B; Dembo M; Hanks S K; Wang Y;
JournalProc Natl Acad Sci U S A
PubMed ID11572981
Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase localized at focal adhesions and is believed to mediate adhesion-stimulated effects. Although ablation of FAK impairs cell movement, it is not clear whether FAK might be involved in the guidance of cell migration, a role consistent with its putative regulatory ... More
Glucocorticoid-mediated repression of NFkappaB activity in endothelial cells does not involve induction of IkappaBalpha synthesis.
Authors Brostjan C; Anrather J; Csizmadia V; Stroka D; Soares M; Bach F H; Winkler H;
JournalJ Biol Chem
PubMed ID8702657
Repression of NFkappaB-dependent gene expression is one of the major elements of immunosuppression by glucocorticoids. Protein-protein interactions between the glucocorticoid receptor and NFkappaB have been characterized and shown to be a possible mechanism of mutual inhibition of transactivation properties. More recently, glucocorticoid-mediated induction of IkappaBalpha, an inhibitor of NFkappaB, has ... More