The gene for the embryonic stem cell coactivator UTF1 carries a regulatory element which selectively interacts with a complex composed of Oct-3/4 and Sox-2.
AuthorsNishimoto M,Fukushima A,Okuda A,Muramatsu M
JournalMolecular and cellular biology
PubMed ID10409735
UTF1 is a transcriptional coactivator which has recently been isolated and found to be expressed mainly in pluripotent embryonic stem (ES) cells (A. Okuda, A. Fukushima, M. Nishimoto, et al., EMBO J. 17:2019â2032, 1998). To gain insight into the regulatory network of gene expression in ES cells, we have characterized ... More
WAF1, a potential mediator of p53 tumor suppression.
Authorsel-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B
JournalCell
PubMed ID8242752
The ability of p53 to activate transcription from specific sequences suggests that genes induced by p53 may mediate its biological role as a tumor suppressor. Using a subtractive hybridization approach, we identified a gene, named WAF1, whose induction was associated with wild- type but not mutant p53 gene expression in ... More
DNA methylation and genetic instability in colorectal cancer cells [see comments]
AuthorsLengauer C, Kinzler KW, Vogelstein B
JournalProc Natl Acad Sci U S A
PubMed ID9122232
'Apparent alterations in DNA methylation have been observed in many cancers, but whether such alterations represent a persistent alteration in the normal methylation process is not known. In this study, we report a striking difference in the expression of exogenously introduced retroviral genes in various colorectal cancer cell lines. Extinguished ... More
Phosphorylation of glycogen synthase kinase-3 and stimulation of T-cell factor signaling following activation of EP2 and EP4 prostanoid receptors by prostaglandin E2.
Authors Fujino Hiromichi; West Kimberly A; Regan John W;
JournalJ Biol Chem
PubMed ID11706038
'Recently we have shown that the FP(B) prostanoid receptor, a G-protein-coupled receptor that couples to Galpha(q), activates T-cell factor (Tcf)/lymphoid enhancer factor (Lef)-mediated transcriptional activation (Fujino, H., and Regan, J. W. (2001) J. Biol. Chem. 276, 12489-12492). We now report that the EP(2) and EP(4) prostanoid receptors, which couple to ... More
The intramembrane cleavage site of the amyloid precursor protein depends on the length of its transmembrane domain.
Authors Lichtenthaler Stefan F; Beher Dirk; Grimm Heike S; Wang Rong; Shearman Mark S; Masters Colin L; Beyreuther Konrad;
JournalProc Natl Acad Sci U S A
PubMed ID11805291
'Proteolytic processing of the amyloid precursor protein by beta-secretase generates C99, which subsequently is cleaved by gamma-secretase, yielding the amyloid beta peptide (A beta). This gamma-cleavage occurs within the transmembrane domain (TMD) of C99 and is similar to the intramembrane cleavage of Notch. However, Notch and C99 differ in their ... More
Cationic lipid-mediated delivery and expression of prepro-neuropeptide Y cDNA after intraventricular administration in rat: feasibility and limitations.
AuthorsThorsell A, Blomqvist AG, Heilig M
JournalRegul Pept
PubMed ID8701037
'The utility of in vivo lipofection for delivery and expression of a neuropeptide gene in the adult rat brain was explored. Prepro-neuropeptide Y (NPY) cDNA was cloned into the episomal eucaryotic expression vector pCEP4. This construct was complexed to lipofectamine or lipofectin. Complexed DNA was injected into the lateral ventricles ... More
Structure and function in rhodopsin: a tetracycline-inducible system in stable mammalian cell lines for high-level expression of opsin mutants.
Authors Reeves Philip J; Kim Jong-Myoung; Khorana H Gobind;
JournalProc Natl Acad Sci U S A
PubMed ID12370422
'Tetracycline-inducible HEK293S stable cell lines have been prepared that express high levels (up to 10 mg/liter) of WT opsin and its mutants only in response to the addition of tetracycline and sodium butyrate. The cell lines were prepared by stable transfection of HEK293S-TetR cells with expression plasmids that contained the ... More
Rapid internalization and recycling of the human neuropeptide Y Y(1) receptor.
'Desensitization of G protein-coupled receptors (GPCRs) involves receptor phosphorylation and reduction in the number of receptors at the cell surface. The neuropeptide Y (NPY) Y(1) receptor undergoes fast desensitization. We examined agonist-induced signaling and internalization using NPY Y(1) receptors fused to green fluorescent protein (EGFP). When expressed in HEK293 cells, ... More
Reconstitution of stretch-activated cation channels by expression of the alpha-subunit of the epithelial sodium channel cloned from osteoblasts [published erratum appears in Proc Natl Acad Sci U S A 1997 Apr 15;94(8):4233]
AuthorsKizer N, Guo XL, Hruska K
JournalProc Natl Acad Sci U S A
PubMed ID9023374
'Osteoblasts respond to repetitive strain by activating stretch- activated, nonselective cation channels (SA-CAT) and increasing matrix protein production. SA-CAT channels are thought to be responsible for mechano-transduction in osteoblasts, although the molecular identity of the SA-CAT channel has previously been unknown. We have demonstrated that both the UMR-106 osteoblast-like cell ... More
Phospholipase D and RalA cooperate with the epidermal growth factor receptor to transform 3Y1 rat fibroblasts.
AuthorsLu Z, Hornia A, Joseph T, Sukezane T, Frankel P, Zhong M, Bychenok S, Xu L, Feig LA, Foster DA
JournalMol Cell Biol
PubMed ID10611224
'3Y1 rat fibroblasts overexpressing the epidermal growth factor (EGF) receptor (EGFR cells) become transformed when treated with EGF. A common response to oncogenic and mitogenic stimuli is elevated phospholipase D (PLD) activity. RalA, a small GTPase that functions as a downstream effector molecule of Ras, exists in a complex with ... More
Multiple Cbfa/AML sites in the rat osteocalcin promoter are required for basal and vitamin D-responsive transcription and contribute to chromatin organization.
AuthorsJaved A, Gutierrez S, Montecino M, van Wijnen AJ, Stein JL, Stein GS, Lian JB
JournalMol Cell Biol
PubMed ID10523637
'Three Cbfa motifs are strategically positioned in the bone-specific rat osteocalcin (rOC) promoter. Sites A and B flank the vitamin D response element in the distal promoter and sites B and C flank a positioned nucleosome in the proximal promoter. The functional significance of each Cbfa element was addressed by ... More
Ligand-mediated negative regulation of a chimeric transmembrane receptor tyrosine phosphatase.
AuthorsDesai DM, Sap J, Schlessinger J, Weiss A
JournalCell
PubMed ID8490965
'CD45, a transmembrane protein tyrosine phosphatase (PTPase), is required for TCR signaling. Multiple CD45 isoforms, differing in the extracellular domain, are expressed in a tissue- and activation- specific manner, suggesting an important function for this domain. We report that a chimeric protein in which the extracellular and transmembrane domains of ... More
Dominant negative effectors of heparin affin regulatory peptide (HARP) angiogenic and transforming activities.
'Heparin affin regulatory peptide (HARP) is an heparin-binding growth factor, highly expressed in several primary human tumors and considered as a rate-limiting angiogenic factor in tumor growth, invasion, and metastasis. Implication of this protein in carcinogenesis is linked to its mitogenic, angiogenic, and transforming activities. Recently, we have demonstrated that ... More
Overexpression of Xenopus laevis growth hormone stimulates growth of tadpoles and frogs.
AuthorsHuang H, Brown DD
JournalProc Natl Acad Sci U S A
PubMed ID10618393
'The role of growth hormone (GH) in amphibian metamorphosis is ambiguous based on experiments in which mammalian GH was administered to tadpoles and frogs. We have reexamined the effects of GH by producing transgenic Xenopus laevis that overexpress the cDNA encoding X. laevis GH. These transgenic tadpoles take the same ... More
Single gene circles in dinoflagellate chloroplast genomes [In Process Citation]
AuthorsZhang Z, Green BR, Cavalier-Smith T
JournalNature
PubMed ID10408440
'Photosynthetic dinoflagellates are important aquatic primary producers and notorious causes of toxic ''red tides''. Typical dinoflagellate chloroplasts differ from all other plastids in having a combination of three envelope membranes and peridinin-chlorophyll a/c light-harvesting pigments. Despite evidence of a dinoflagellete satellite DNA containing chloroplast genes, previous attempts to obtain chloroplast ... More
Nectin2alpha (PRR2alpha or HveB) and nectin2delta are low-efficiency mediators for entry of herpes simplex virus mutants carrying the Leu25Pro substitution in glycoprotein D.
AuthorsLopez M, Cocchi F, Menotti L, Avitabile E, Dubreuil P, Campadelli-Fiume G
JournalJ Virol
PubMed ID10627537
'The receptors for entry of herpes simplex viruses 1 and 2 (HSV-1 and -2), widely expressed in human cell lines, are members of a subset of the immunoglobulin superfamily exemplified by herpesvirus entry mediator C (HveC) and the herpesvirus immunoglobulin-like receptor (HIgR). This report focuses on two members of this ... More
p200 ARFûGEP1: A Golgi-localized guanine nucleotide exchange protein whose Sec7 domain is targeted by the drug brefeldin A
'The drug brefeldin A (BFA) disrupts protein traffic and Golgi morphology by blocking activation of ADP ribosylation factors (ARFs) through an unknown mechanism. Here, we investigated the cellular localization and BFA sensitivity of human p200 ARF-GEP1 (p200), a ubiquitously expressed guanine nucleotide exchange factor of the Sec7 domain family. Multiple ... More
Site-specific chemical modification of recombinant proteins produced in mammalian cells by using the genetically encoded aldehyde tag.
AuthorsWu P, Shui W, Carlson BL, Hu N, Rabuka D, Lee J, Bertozzi CR,
JournalProc Natl Acad Sci U S A
PubMed ID19202059
'The properties of therapeutic proteins can be enhanced by chemical modification. Methods for site-specific protein conjugation are critical to such efforts. Here, we demonstrate that recombinant proteins expressed in mammalian cells can be site-specifically modified by using a genetically encoded aldehyde tag. We introduced the peptide sequence recognized by the ... More
Signal transduction through a biomolecular receptor tyrosine protein kinase composed of a platelet-derived growth factor receptor-CD4 chimera and the nonreceptor tyrosine protein kinase Lck.
'We have generated a novel receptor tyrosine kinase by fusing the extracellular and transmembrane domain of the mouse platelet-derived growth factor receptor (PDGFR) to the cytoplasmic domain of CD4 and coexpressing the construct with the murine cytoplasmic tyrosine protein kinase p56lck. NMuMG cells, which are mouse mammary gland epithelial cells ... More
Phosphorylation of insulin receptor substrate-1 on multiple serine residues, 612, 632, 662, and 731, modulates insulin action.
AuthorsMothe I, Van Obberghen E
JournalJ Biol Chem
PubMed ID8626671
'Okadaic acid has been described previously as being a negative regulator of insulin signaling, as it inhibits insulin stimulation of glucose transport. In addition, this drug induces on insulin receptor substrate-1 (IRS-1) a decrease in tyrosine phosphorylation, concomitantly with an increase in serine/threonine phosphorylation. The present work was aimed at ... More
Cyclic AMP-dependent activation of Rap1b.
Authors Altschuler D L; Peterson S N; Ostrowski M C; Lapetina E G;
JournalJ Biol Chem
PubMed ID7737967
'Rap1 proteins belong to the Ras superfamily of small molecular weight GTP-binding proteins. Although Rap1 and Ras share approximately 50% overall amino acid sequence identity, the effector domains of the two proteins are identical, suggesting either similar or antagonistic signaling roles. Several pathways leading to Ras activation have been defined, ... More
Alanine-scanning mutagenesis of a C-terminal ligand binding domain of the insulin receptor alpha subunit [published erratum appears in J Biol Chem 1996 Nov 22;271(47):30297]
AuthorsMynarcik DC, Yu GQ, Whittaker J
JournalJ Biol Chem
PubMed ID8576204
'A recent affinity labeling study has suggested that amino acids 704-717 of the C terminus of the insulin receptor represent a contact site for insulin. To determine whether these amino acids are part of a ligand binding site, we have performed alanine-scanning mutagenesis of this region. Mutant cDNAs encoding recombinant ... More
Simian virus 40 small t antigen cooperates with mitogen-activated kinases to stimulate AP-1 activity.
AuthorsFrost JA, Alberts AS, Sontag E, Guan K, Mumby MC, Feramisco JR
JournalMol Cell Biol
PubMed ID8065356
'The simian virus 40 small tumor antigen (small t) specifically interacts with protein phosphatase type 2A (PP2A) in vivo and alters its catalytic activity in vitro. Among the substrates for PP2A in vitro are the activated forms of MEK and ERK kinases. Dephosphorylation of the activating phosphorylation sites on MEK ... More
Mitogen-activated protein kinase-mediated Fas apoptotic signaling pathway.
AuthorsGoillot E, Raingeaud J, Ranger A, Tepper RI, Davis RJ, Harlow E, Sanchez I
JournalProc Natl Acad Sci U S A
PubMed ID9096388
'Ligation of the cell surface receptor Fas/APO-1 (CD95) by its specific ligand or by anti-Fas antibodies rapidly induces apoptosis in susceptible cells. To characterize the molecular events involved in Fas- induced apoptosis, we examined the contribution of two subgroups of the mitogen-activated protein (MAP) kinase family, the Jun kinases or ... More
p40(phox) down-regulates NADPH oxidase activity through interactions with its SH3 domain.
AuthorsSathyamoorthy M, de Mendez I, Adams AG, Leto TL
JournalJ Biol Chem
PubMed ID9083043
'The NADPH oxidase of phagocytes generates microbicidal oxidants in response to a variety of stimuli. Its activation and assembly involve multiple SH3 domain interactions among several oxidase components. Here we present evidence that the cytosolic oxidase-associated protein, p40(phox), mediates down-regulation of NADPH oxidase through interactions with its SH3 domain. ... More
Formation of stable complexes between two Alzheimer's disease gene products: presenilin-2 and beta-amyloid precursor protein.
AuthorsWeidemann A, Paliga K, Durrwang U, Czech C, Evin G, Masters CL, Beyreuther K
JournalNat Med
PubMed ID9055862
'Mutations in the presenilin genes are associated with early onset familial Alzheimer''s disease and lead to increased accumulation of beta A4 peptide, the proteolytic product of the amyloid precursor protein (APP). To test whether presenilins interfere with APP metabolism, presenilin-2 (PS2) was coexpressed with APP in mammalian cells. Analysis of ... More
Phosphorylation-dependent block of cystic fibrosis transmembrane conductance regulator chloride channel by exogenous R domain protein.
AuthorsMa J, Tasch JE, Tao T, Zhao J, Xie J, Drumm ML, Davis PB
JournalJ Biol Chem
PubMed ID8631756
'The cystic fibrosis transmembrane conductance regulator (CFTR) constitutes a linear conductance chloride channel, which is regulated by cAMP-dependent protein kinase phosphorylation at multiple sites located in the intracellular regulatory (R) domain. Studies in a lipid bilayer system, reported here, provide evidence for the control of CFTR chloride channel by its ... More
The human CD46 molecule is a receptor for measles virus (Edmonston strain).
AuthorsDorig RE, Marcil A, Chopra A, Richardson CD
JournalCell
PubMed ID8402913
'Measles virus normally causes disease in human beings, and the host range of this virus may be determined by a specific receptor on the surface of primate cells. Human-rodent somatic cell hybrids were tested for their ability to bind measles virus, and only cells that contained human chromosome 1 were ... More
Jak3 is associated with CD40 and is critical for CD40 induction of gene expression in B cells.
AuthorsHanissian SH, Geha RS
JournalImmunity
PubMed ID9133417
'CD40 is a receptor that is critical for the survival, growth, differentiation, and isotype switching of B lymphocytes. Although CD40 lacks intrinsic tyrosine kinase activity, its ligation induces protein tyrosine phosphorylation, which is necessary for several CD40-mediated events. We show that engagement of CD40 induces tyrosine phosphorylation and activation of ... More
Exon Shuffling by L1 Retrotransposition
AuthorsJohn V. Moran, * Ralph J. DeBerardinis, Haig H. Kazazian Jr.
JournalScience
PubMed ID10066175
Long interspersed nuclear elements (LINE-1s or L1s) are the mostabundant retrotransposons in the human genome, and they serve asmajor sources of reverse transcriptase activity. Engineered L1sretrotranspose at high frequency in cultured human cells. Here it isshown that L1s insert into transcribed genes and retrotransposesequences derived from their 3' flanks to ... More
Dopaminergic Loss and Inclusion Body Formation in -Synuclein Mice: Implications for Neurodegenerative Disorders
AuthorsMasliah E, Rockenstein E, Veinbergs I, Mallory M, Hashimoto M, Takeda A, Sagara Y, Sisk A, Mucke L
JournalScience
PubMed ID10678833
To elucidate the role of the synaptic protein alpha-synuclein in neurodegenerative disorders, transgenic mice expressing wild-type human alpha-synuclein were generated. Neuronal expression of human alpha-synuclein resulted in progressive accumulation of alpha-synuclein-and ubiquitin-immunoreactive inclusions in neurons in the neocortex, hippocampus, and substantia nigra. Ultrastructural analysis revealed both electron-dense intranuclear deposits and ... More
A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle [published erratum appears in Proc Natl Acad Sci U S A 1995 Apr 25;92(9):4074]
AuthorsKishimoto T, Pearse RV 2nd, Lin CR, Rosenfeld MG
JournalProc Natl Acad Sci U S A
PubMed ID7755719
Corticotropin-releasing factor (CRF) mediates many critical aspects of the physiological response to stress. These effects are elicited by binding to specific high-affinity receptors, which are coupled to guanine nucleotide stimulatory factor (Gs)-response pathways. Recently, a gene encoding a receptor for CRF, expressed in pituitary and the central nervous system (PC-CRF ... More
Modified miniprep method for the rapid recovery of episomes from transfected breast epithelial cells.
AuthorsBowers MT, Ramachandran S, Yu BW
JournalBiotechniques
PubMed ID10023539
Episomal vectors such as pCEP4 are useful in expression cloning because they can replicate in both prokaryotes and eukaryotic cells. We have found a rapid and efficient means of extracting them from transfected MCF-10A nonmalignant human breast epithelial cells. We show that a plasmid miniprep protocol, modified by the addition ... More
Hot-spot p53 mutants interact specifically with two cellular proteins during progression of the cell cycle.
AuthorsChen Y, Chen PL, Lee WH
JournalMol Cell Biol
PubMed ID7935394
Inactivation of both alleles of the p53 gene is commonly found in human cancers. In contrast to mutations of the retinoblastoma gene, certain altered forms of p53 gain growth-promoting functions. To explore the mechanisms underlying this gain of function, we have identified two nuclear proteins, with molecular masses of 42 ... More
Osteoprotegerin: a novel secreted protein involved in the regulation of bone density [see comments]
AuthorsSimonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Boyle WJ, et al
JournalCell
PubMed ID9108485
A novel secreted glycoprotein that regulates bone resorption has been identified. The protein, termed Osteoprotegerin (OPG), is a novel member of the TNF receptor superfamily. In vivo, hepatic expression of OPG in transgenic mice results in a profound yet nonlethal osteopetrosis, coincident with a decrease in later stages of osteoclast ... More
Hypoxia-inducible factor 1alpha protein expression is controlled by oxygen-regulated ubiquitination that is disrupted by deletions and missense mutations.
AuthorsSutter CH, Laughner E, Semenza GL
JournalProc Natl Acad Sci U S A
PubMed ID10758161
Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that mediates cellular and systemic homeostatic responses to reduced O(2) availability in mammals, including angiogenesis, erythropoiesis, and glycolysis. HIF-1 activity is controlled by the O(2)-regulated expression of the HIF-1alpha subunit. Under nonhypoxic conditions, HIF-1alpha protein is subject to ubiquitination and proteasomal degradation. ... More
The semaphorin family contains a large number of phylogenetically conserved proteins and includes several members that have been shown to function in repulsive axon guidance. Semaphorin III (Sema III) is a secreted protein that in vitro causes neuronal growth cone collapse and chemorepulsion of neurites, and in vivo is required ... More
Activation of c-Jun N-terminal kinase antagonizes an anti-apoptotic action of Bcl-2.
AuthorsPark J, Kim I, Oh YJ, Lee K, Han PL, Choi EJ
JournalJ Biol Chem
PubMed ID9201973
Bcl-2 is an intracellular membrane-associated protein that prevents cell death induced by a variety of apoptotic stimuli. A mechanism by which Bcl-2 exerts an anti-cell death effect is, however, not fully understood. In the present study, Bcl-2 suppressed cell death of N18TG neuroglioma cells caused by various apoptotic stresses, including ... More
Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
AuthorsLacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ
JournalCell
PubMed ID9568710
The ligand for osteoprotegerin has been identified, and it is a TNF- related cytokine that replaces the requirement for stromal cells, vitamin D3, and glucocorticoids in the coculture model of in vitro osteoclastogenesis. OPG ligand (OPGL) binds to a unique hematopoeitic progenitor cell that is committed to the osteoclast lineage ... More
Somatic hypermutation of the AID transgene in B and non-B cells.
Authors Martin Alberto; Scharff Matthew D;
JournalProc Natl Acad Sci U S A
PubMed ID12202747
Somatic hypermutation (SHM) of the Ig genes is required for affinity maturation of the humoral response to foreign antigens. Activation-induced cytidine deaminase (AID), which is specifically expressed in germinal center centroblasts, is indispensable for this process. Expression of AID is sufficient to activate SHM in hybridomas, non-B cells, and Escherichia ... More
Neuropilin is a receptor for the axonal chemorepellent Semaphorin III.
AuthorsHe Z, Tessier-Lavigne M
JournalCell
PubMed ID9288753
Extending axons in the developing nervous system are guided to their targets through the coordinate actions of attractive and repulsive guidance cues. The semaphorin family of guidance cues comprises several members that can function as diffusible axonal chemorepellents. To begin to elucidate the mechanisms that mediate the repulsive actions of ... More
Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry.
AuthorsFarzan M, Mirzabekov T, Kolchinsky P, Wyatt R, Cayabyab M, Gerard NP, Gerard C, Sodroski J, Choe H
JournalCell
PubMed ID10089882
Chemokine receptors and related seven-transmembrane-segment (7TMS) receptors serve as coreceptors for entry of human and simian immunodeficiency viruses (HIV-1, HIV-2, and SIV) into target cells. Each of these otherwise diverse coreceptors contains an N-terminal region that is acidic and tyrosine rich. Here, we show that the chemokine receptor CCR5, a ... More
The cytoplasmic domain of granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha subunit is essential for both GM-CSF- mediated growth and differentiation.
AuthorsMatsuguchi T, Zhao Y, Lilly MB, Kraft AS
JournalJ Biol Chem
PubMed ID9211889
Granulocyte-macrophage colony-stimulating factor (GM-CSF) regulates differentiation, survival, and proliferation of colony-forming unit- granulocyte-macrophage progenitor cells. The biologic actions of GM-CSF are mediated by binding to a specific receptor consisting of two chains designated as alpha and beta subunits. We have demonstrated that the murine FDC-P1-derived cell line WT-19 transfected with ... More
Presentation on class II MHC molecules of endogenous lysozyme targeted to the endocytic pathway.
AuthorsParra-Lopez CA, Lindner R, Vidavsky I, Gross M, Unanue ER
JournalJ Immunol
PubMed ID9058800
We compared the processing and presentation of the model Ag, hen-egg white lysozyme (HEL) expressed in C3.F6 APC as a fusion protein to three different acid hydrolases: cathepsin D, to an unglycosylated form of cathepsin D, and to pepsinogen. As expected from the biology of mannose 6-phosphate (Man-6-P)-containing enzyme, cathepsin ... More
Molecular cloning, characterization, and regulation of the human mitochondrial serine hydroxymethyltransferase gene.
The human mitochondrial serine hydroxymethyltransferase (mSHMT) gene was isolated, sequenced, and characterized. The 4.5-kilobase gene contains 10 introns and 11 exons, with all splice junctions conforming to the GT/AG rule. The 5' promoter region contains consensus motifs for several regulatory proteins including PEA-3, Sp-1, AP-2, and a CCCTCCC motif common ... More
Specific induction of cell motility on laminin by alpha 7 integrin.
AuthorsEchtermeyer F, Schober S, Poschl E, von der Mark H, von der Mark K
JournalJ Biol Chem
PubMed ID8567661
Laminin, the major glycoprotein of basement membranes, actively supports cell migration in development, tissue repair, tumor growth, metastasis, and other pathological processes. Previously we have shown that the locomotion of murine skeletal myoblasts is specifically and significantly enhanced on laminin but not on other matrix proteins. One of the major ... More
Expression of a peptide inhibitor of protein phosphatase 1 increases phosphorylation and activity of CREB in NIH 3T3 fibroblasts.
AuthorsAlberts AS, Montminy M, Shenolikar S, Feramisco JR
JournalMol Cell Biol
PubMed ID7516466
We have examined the activity and phosphorylation state of the cyclic AMP (cAMP) response element binding factor (CREB) in intact NIH 3T3 cells following microinjection of expression plasmids encoding regulatory proteins of type 1 (PP1) and 2A (PP2A) serine/threonine- specific protein phosphatases. Changes in CREB phosphorylation in the injected cells ... More
The fibroblast growth factor receptor-4 Arg388 allele is associated with prostate cancer initiation and progression.
AuthorsWang J, Stockton DW, Ittmann M,
JournalClin Cancer Res
PubMed ID15448004
PURPOSE: Increased expression of fibroblast growth factors that can activate the fibroblast growth factor receptor-4 (FGFR-4) occurs in a substantial fraction of human prostate cancers in vivo. A germline polymorphism of the FGFR-4 gene resulting in expression of arginine at codon 388 (Arg388) is associated with aggressive disease in patients ... More
Specific antagonism of type I IL-4 receptor with a mutated form of murine IL-4.
AuthorsSchnare M, Blum H, Juttner S, Rollinghoff M, Gessner A
JournalJ Immunol
PubMed ID9759868
IL-4 is a pleiotropic cytokine that is essential for the differentiation of Th2 cells and is critically involved in the pathogenesis of certain infectious and allergic diseases. We have produced and functionally characterized a mutant of murine IL-4 (IL- 4.Y119D) as a potential antagonist of IL-4. The analysis of IL-4R ... More
Sequence-specific transcriptional activation is essential for growth suppression by p53.
Although several biochemical features of p53 have been described, their relationship to tumor suppression remains uncertain. We have compared the ability of p53-derived proteins to act as sequence-specific transcriptional (SST) activators with their ability to suppress tumor cell growth, using an improved growth-suppression assay. Both naturally occurring and in vitro ... More
The regulation of anoikis: MEKK-1 activation requires cleavage by caspases.
AuthorsCardone MH, Salvesen GS, Widmann C, Johnson G, Frisch SM
JournalCell
PubMed ID9244305
Certain cell types undergo apoptosis when they lose integrin-mediated contacts with the extracellular matrix (anoikis). The Jun N-terminal kinase (JNK) pathway is activated in and promotes anoikis. This activation requires caspase activity. We presently report that a DEVD motif-specific caspase that cleaves MEKK-1 specifically is activated when cells lose matrix ... More
The opioid system modulates several physiological processes, including analgesia, the stress response, the immune response and neuroendocrine function. Pharmacological and molecular cloning studies have identified three opioid-receptor types, delta, kappa and mu, that mediate these diverse effects. Little is known about the ability of the receptors to interact to form ... More
RtsA and RtsB Coordinately Regulate Expression of the Invasion and Flagellar Genes in Salmonella enterica Serovar Typhimurium.
AuthorsEllermeier CD, Slauch JM,
JournalJ Bacteriol
PubMed ID12923082
Salmonella enterica serovar Typhimurium encounters numerous host environments and defense mechanisms during the infection process. The bacterium responds by tightly regulating the expression of virulence genes. We identified two regulatory proteins, termed RtsA and RtsB, which are encoded in an operon located on an island integrated at tRNA(PheU) in S. ... More
Construction and characterization of a fusion protein of single-chain anti-CD20 antibody and human beta-glucuronidase for antibody-directed enzyme prodrug therapy.
AuthorsHaisma HJ, Sernee MF, Hooijberg E, Brakenhoff RH, v.d. Meulen-Muileman IH, Pinedo HM, Boven E
JournalBlood
PubMed ID9639515
The CD20 antigen is an attractive target for specific treatment of B- cell lymphoma. Antibody-directed enzyme prodrug therapy (ADEPT) aims at the specific activation of a nontoxic prodrug at the tumor site by an enzyme targeted by a tumor-specific antibody such as anti-CD20. We constructed a fusion protein of the ... More
Homodimerization of the human interleukin 4 receptor alpha chain induces Cepsilon germline transcripts in B cells in the absence of the interleukin 2 receptor gamma chain.
AuthorsFujiwara H, Hanissian SH, Tsytsykova A, Geha RS
JournalProc Natl Acad Sci U S A
PubMed ID9159166
The cytokines interleukin (IL)-4 and IL-13 play a critical role in inducing Cepsilon germline transcripts and IgE isotype switching in human B cells. The IL-4 receptor (IL-4R) in B cells is composed of two chains, the IL-4-binding IL-4Ralpha chain, which is shared with the IL- 13R, and the IL-2Rgamma (gammac) ... More
Epstein-Barr virus shuttle vector for stable episomal replication of cDNA expression libraries in human cells.
AuthorsMargolskee RF, Kavathas P, Berg P,
JournalMol Cell Biol
PubMed ID2841588
Efficient transfection and expression of cDNA libraries in human cells has been achieved with an Epstein-Barr virus-based subcloning vector (EBO-pcD). The plasmid vector contains a resistance marker for hygromycin B to permit selection for transformed cells. The Epstein-Barr virus origin for plasmid replication (oriP) and the Epstein-Barr virus nuclear antigen ... More
Effect of bronchoalveolar lavage fluid from Pneumocystis carinii-infected hosts on phagocytic activity of alveolar macrophages.
AuthorsLasbury ME, Lin P, Tschang D, Durant PJ, Lee CH,
JournalInfect Immun
PubMed ID15039336
Alveolar macrophages from Pneumocystis carinii-infected rats are defective in phagocytosis. To investigate whether this defect is due to a certain factor present in P. carinii-infected lungs, alveolar macrophages from uninfected rats were incubated with bronchoalveolar lavage (BAL) fluid samples from P. carinii-infected rats. Alveolar macrophages treated with these BAL fluid ... More
AP-4 binds basolateral signals and participates in basolateral sorting in epithelial MDCK cells.
Adaptors are heterotetrameric complexes that mediate the incorporation of cargo into transport vesicles by interacting with sorting signals present in the cytosolic domain of transmembrane proteins. Four adaptors, AP-1 (beta1, gamma, &mgr;1A or &mgr;1B, sigma1), AP-2 (beta2, alpha, &mgr;2, sigma2), AP-3 (beta3, delta, &mgr;3, sigma3) or AP-4 (beta4, var epsilon, ... More
Activation-induced cytidine deaminase turns on somatic hypermutation in hybridomas.
Authors Martin Alberto; Bardwell Philip D; Woo Caroline J; Fan Manxia; Shulman Marc J; Scharff Matthew D;
JournalNature
PubMed ID11823785
The production of high-affinity protective antibodies requires somatic hypermutation (SHM) of the antibody variable (V)-region genes. SHM is characterized by a high frequency of point mutations that occur only during the centroblast stage of B-cell differentiation. Activation-induced cytidine deaminase (AID), which is expressed specifically in germinal-centre centroblasts, is required for ... More
Selective induction of neuropilin-1 by vascular endothelial growth factor (VEGF): a mechanism contributing to VEGF-induced angiogenesis.
Neuropilin (NRP) 1, previously identified as a neuronal receptor that mediates repulsive growth cone guidance, has been shown recently to function also in endothelial cells as an isoform-specific receptor for vascular endothelial growth factor (VEGF)(165) and as a coreceptor in vitro of VEGF receptor 2. However, its potential role in ... More
Cathepsin B mediates tumor necrosis factor-induced arachidonic acid release in tumor cells.
AuthorsFoghsgaard L, Lademann U, Wissing D, Poulsen B, Jaattela M
JournalJ Biol Chem
PubMed ID12185082
Arachidonic acid (AA) generated by cytosolic phospholipase A2 (cPLA2) has been suggested to function as a second messenger in tumor necrosis factor (TNF)-induced death signaling. Here, we show that cathepsin B-like proteases are required for the TNF-induced AA release in transformed cells. Pharmaceutical inhibitors of cathepsin B blocked TNF-induced AA ... More
Homodimerization of amyloid precursor protein and its implication in the amyloidogenic pathway of Alzheimer's disease.
Authors Scheuermann S; Hambsch B; Hesse L; Stumm J; Schmidt C; Beher D; Bayer T A; Beyreuther K; Multhaup G;
JournalJ Biol Chem
PubMed ID11438549
We reported previously that the carbohydrate domain of the amyloid precursor protein is involved in amyloid precursor protein (APP)-APP interactions. Functional in vitro studies suggested that this interaction occurs through the collagen binding site of APP. The physiological significance remained unknown, because it is not understood whether and how APP ... More
A short segment of the R domain of cystic fibrosis transmembrane conductance regulator contains channel stimulatory and inhibitory activities that are separable by sequence modification.
Authors Xie Junxia; Adams Lynn M; Zhao Jiying; Gerken Thomas A; Davis Pamela B; Ma Jianjie;
JournalJ Biol Chem
PubMed ID11950844
The regulatory (R) domain of the cystic fibrosis transmembrane conductance regulator (CFTR) contains consensus phosphorylation sites for cAMP-dependent protein kinase (PKA) that are the basis for physiological regulation of the CFTR chloride channel. A short peptide segment in the R domain with a net negative charge of B9 (amino acids ... More
Cloning and characterization of ADAMTS-14, a novel ADAMTS displaying high homology with ADAMTS-2 and ADAMTS-3.
Authors Colige Alain; Vandenberghe Isabel; Thiry Marc; Lambert Charles A; Van Beeumen Jozef; Li Shi-Wu; Prockop Darwin J; Lapiere Charles M; Nusgens Betty V;
JournalJ Biol Chem
PubMed ID11741898
The processing of amino- and carboxyl-propeptides of fibrillar collagens is required to generate collagen monomers that correctly assemble into fibrils. Mutations in the ADAMTS2 gene, the aminopropeptidase of procollagen I and II, result in the accumulation of non-fully processed type I procollagen, causing human Ehlers-Danlos syndrome type VIIC and animal ... 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
Trafficking and cell surface stability of the epithelial na+ channel expressed in epithelial madin-darby canine kidney cells.
The apically located epithelial Na(+) channel (alphabetagamma-ENaC) plays a key role in the regulation of salt and fluid transport in the kidney and other epithelia, yet its mode of trafficking to the plasma membrane and its cell surface stability in mammalian cells are poorly understood. Because the expression of ENaC ... More
Collagen X Chains Harboring Schmid Metaphyseal Chondrodysplasia NC1 Domain Mutations Are Selectively Retained and Degraded in Stably Transfected Cells.
Authors Wilson Richard; Freddi Susanna; Bateman John F;
JournalJ Biol Chem
PubMed ID11805116
Collagen X is a short chain, homotrimeric collagen expressed specifically by hypertrophic chondrocytes during endochondral bone formation and growth. Although the exact role of collagen X remains unresolved, mutations in the COL10A1 gene disrupt growth plate function and result in Schmid metaphyseal chondrodysplasia (SMCD). With the exception of two mutations ... More
Antigenic and Functional Properties of the Human Red Blood Cell Urea Transporter hUT-B1.
The Kidd (JK) blood group locus encodes the urea transporter hUT-B1, which is expressed on human red blood cells and other tissues. The common JK*A/JK*B blood group polymorphism is caused by a single nucleotide transition G838A changing Asp-280 to Asn-280 on the polypeptide, and transfection of erythroleukemic K562 cells with ... More