Cloning and functional expression of a thyrotropin receptor cDNA from rat fat cells.
AuthorsEndo T; Ohta K; Haraguchi K; Onaya T;
JournalJ Biol Chem
PubMed ID7738021
Thyrotropin receptor (TSH-R) has been thought to be thyroid-specific, but, by Northern blot analysis, we found that rat adipose tissue expressed TSH-R mRNAs in amounts approaching those in the thyroid. To investigate the function of TSH-R from adipose tissue, we screened a rat fat cell lambda gt11 cDNA library for ... More
Residues throughout the cytoplasmic domain affect the internalization efficiency of P-selectin.
Authors Setiadi H; Disdier M; Green S A; Canfield W M; McEver R P;
JournalJ Biol Chem
PubMed ID7592923
'The cytoplasmic domains of many membrane proteins have short sequences, usually including a tyrosine or a di-leucine, that function as sorting signals. P-selectin is an adhesion receptor for leukocytes that is expressed on activated platelets and endothelial cells. Its 35-residue cytoplasmic domain contains signals for sorting into regulated secretory granules, ... More
Structural basis of G protein specificity of human endothelin receptors. A study with endothelinA/B chimeras.
'The endothelin (ET) family of peptides acts via two subtypes of guanine nucleotide-binding regulatory protein (G protein)-coupled receptors termed ETA and ETB. ET-1 stimulated cAMP formation in Chinese hamster ovary (CHO) cells stably expressing human wild-type ETA (CHO/hETA cells) while it inhibited cAMP formation in CHO cells expressing human wild-type ... More
Fli-1, an Ets-related transcription factor, regulates erythropoietin- induced erythroid proliferation and differentiation: evidence for direct transcriptional repression of the Rb gene during differentiation.
AuthorsTamir A, Howard J, Higgins RR, Li YJ, Berger L, Zacksenhaus E, Reis M, Ben-David Y
JournalMol Cell Biol
PubMed ID10330185
'Erythropoietin (Epo) is a major regulator of erythropoiesis that alters the survival, proliferation, and differentiation of erythroid progenitor cells. The mechanism by which these events are regulated has not yet been determined. Using HB60, a newly established erythroblastic cell line, we show here that Epo-induced terminal erythroid differentiation is associated ... More
Distinct STAT structure promotes interaction of STAT2 with the p48 subunit of the interferon-alpha-stimulated transcription factor ISGF3.
AuthorsMartinez-Moczygemba M, Gutch MJ, French DL, Reich NC
JournalJ Biol Chem
PubMed ID9242679
'Cells express a variety of STAT (signal transducer and activator of transcription) transcription factors that are structurally homologous and yet function specifically in response to particular cytokines. The functions of the individual STATs are dependent on distinct protein- protein interactions. STAT1 and STAT2 are activated by tyrosine phosphorylation in response ... More
Presenilins are processed by caspase-type proteases.
AuthorsLoetscher H, Deuschle U, Brockhaus M, Reinhardt D, Nelboeck P, Mous J, Grunberg J, Haass C, Jacobsen H
JournalJ Biol Chem
PubMed ID9252383
'Presenilin 1 (PS1) and presenilin 2 (PS2) are endoproteolytically processed in vivo and in cell transfectants to yield 27-35-kDa N- terminal and 15-24-kDa C-terminal fragments. We have studied the cleavage of PS1 and PS2 in transiently and stably transfected hamster kidney and mouse and human neuroblastoma cells by immunoblot and ... More
Dopamine beta-monooxygenase signal/anchor sequence alters trafficking of peptidylglycine alpha-hydroxylating monooxygenase.
Authors Oyarce A M; Steveson T C; Jin L; Eipper B A;
JournalJ Biol Chem
PubMed ID11418593
'Dopamine beta-monooxygenase (DBM) and peptidylglycine alpha-hydroxylating monooxygenase (PHM) are essential for the biosynthesis of catecholamines and amidated peptides, respectively. The enzymes share a conserved catalytic core. We studied the role of the DBM signal sequence by appending it to soluble PHM (PHMs) and expressing the DBMsignal/PHMs chimera in AtT-20 and ... More
Molecular cloning and identification of 3'-phosphoadenosine 5'-phosphosulfate transporter.
AuthorsKamiyama S, Suda T, Ueda R, Suzuki M, Okubo R, Kikuchi N, Chiba Y, Goto S, Toyoda H, Saigo K, Watanabe M, Narimatsu H, Jigami Y, Nishihara S,
JournalJ Biol Chem
PubMed ID12716889
'Nucleotide sulfate, namely 3''-phosphoadenosine 5''-phosphosulfate (PAPS), is a universal sulfuryl donor for sulfation. Although a specific PAPS transporter is present in Golgi membrane, no study has reported the corresponding gene. We have identified a novel human gene encoding a PAPS transporter, which we have named PAPST1, and the Drosophila melanogaster ... More
Targeted disruption of the MKK4 gene causes embryonic death, inhibition of c-Jun NH2-terminal kinase activation, and defects in AP-1 transcriptional activity.
AuthorsYang D, Tournier C, Wysk M, Lu HT, Xu J, Davis RJ, Flavell RA,
JournalProc Natl Acad Sci U S A
PubMed ID9096336
'MKK4 is a member of the mitogen-activated protein kinase kinase group of dual specificity protein kinases that functions as an activator of the c-Jun NH2-terminal kinase (JNK) in vitro. To examine the function of MKK4 in vivo, we investigated the effect of targeted disruption of the MKK4 gene. Crosses of ... More
Costimulation of T cell activation by integrin-associated protein (CD47) is an adhesion-dependent, CD28-independent signaling pathway.
AuthorsReinhold MI, Lindberg FP, Kersh GJ, Allen PM, Brown EJ
JournalJ Exp Med
PubMed ID8996237
'The integrin-associated protein (IAP, CD47) is a 50-kD plasma membrane protein with a single extracellular immunoglobulin variable (IgV)-like domain, a multiply membrane-spanning segment, and alternatively spliced short cytoplasmic tails. On neutrophils, IAP has been shown to function in a signaling complex with beta 3 integrins. However, the function of IAP ... More
Ligand binding to macrophage scavenger receptor-A induces urokinase- type plasminogen activator expression by a protein kinase-dependent signaling pathway.
AuthorsHsu HY, Hajjar DP, Khan KM, Falcone DJ
JournalJ Biol Chem
PubMed ID9422792
'Macrophage scavenger receptor-type A (MSR-A) has been implicated in the transmission of cell signals and the regulation of diverse cellular functions (Falcone, D. J., and Ferenc, M. J. (1988) J. Cell. Physiol. 135, 387-396; Falcone, D. J., McCaffrey, T. A., and Vergilio, J. A. (1991) J. Biol. Chem. 266, 22726-22732; ... More
Prostaglandin E2 amplifies cytosolic phospholipase A2- and cyclooxygenase-2-dependent delayed prostaglandin E2 generation in mouse osteoblastic cells. Enhancement by secretory phospholipase A2.
AuthorsMurakami M, Kuwata H, Amakasu Y, Shimbara S, Nakatani Y, Atsumi G, Kudo I
JournalJ Biol Chem
PubMed ID9242654
'We used the MC3T3-E1 cell line, which originates from C57BL/6J mouse that is genetically type IIA secretory phospholipase A2 (sPLA2)- deficient, to reveal the type IIA sPLA2-independent route of the prostanglandin (PG) biosynthetic pathway. Kinetic and pharmacological studies showed that delayed PGE2 generation by this cell line in response to ... More
Molecular cloning and characterization of a novel UDP-Gal:GalNAc(alpha) peptide beta 1,3-galactosyltransferase (C1Gal-T2), an enzyme synthesizing a core 1 structure of O-glycan.
AuthorsKudo T, Iwai T, Kubota T, Iwasaki H, Takayma Y, Hiruma T, Inaba N, Zhang Y, Gotoh M, Togayachi A, Narimatsu H,
JournalJ Biol Chem
PubMed ID12361956
'Recently, a UDP-Gal:GalNAc(alpha) peptide beta1,3-galactosyltransferase (core 1 synthase 1; C1Gal-T1) has been purified from rat liver and its complementary DNA cloned from several species. We isolated a second candidate for core 1 synthase from a Colo205 cDNA library and named it C1Gal-T2. The deduced amino acid sequence of C1Gal-T2, having ... More
Alternatively spliced products CC3 and TC3 have opposing effects on apoptosis.
AuthorsWhitman S, Wang X, Shalaby R, Shtivelman E.
JournalMol Cell Biol
PubMed ID10611237
'The human gene CC3 is a metastasis suppressor for small cell lung carcinoma (SCLC) in vivo. The ability of CC3 to impair the apoptotic resistance of tumor cells is likely to contribute to metastasis suppression. We describe here an alternatively spliced RNA of CC3, designated TC3, that encodes an unstable ... 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
Herbimycin A induces the 20 S proteasome- and ubiquitin-dependent degradation of receptor tyrosine kinases.
Authors Sepp-Lorenzino L; Ma Z; Lebwohl D E; Vinitsky A; Rosen N;
JournalJ Biol Chem
PubMed ID7622464
'Herbimycin A is an ansamycin antibiotic isolated as an agent that reverses morphological transformation induced by v-src. Although herbimycin A is widely used as a tool for inhibiting multiple tyrosine protein kinases and tyrosine kinase-activated signal transduction, its mechanism of action is not well defined and includes a decrease in ... More
The rBAT gene is responsible for L-cystine uptake via the b0,(+)-like amino acid transport system in a renal proximal tubular cell line (OK cells).
AuthorsMora C, Chillaron J, Calonge MJ, Forgo J, Testar X, Nunes V, Murer H, Zorzano A, Palacin M
JournalJ Biol Chem
PubMed ID8631857
'Several studies have shown that the cRNA of human, rabbit, or rat rBAT induces in Xenopus oocytes sodium-independent, high affinity uptake of L-cystine via a system b0,(+)-like amino acid exchanger. We have shown that mutations in rBAT cause type I cystinuria (Calonge, M. J., Gasparini, P., Chillaron, J., Chillon, M., ... More
Functional role of arginine 373 in substrate translocation by the reduced folate carrier.
AuthorsSadlish H, Williams FM, Flintoff WF,
JournalJ Biol Chem
PubMed ID12194981
'The reduced folate carrier (RFC) plays a critical role in the cellular uptake of folates. However, little is known regarding the mechanism used to transport substrates or the tertiary structure of the protein. Through the analysis of a Chinese hamster ovary cell line deficient in folate uptake, we have identified ... More
Transforming growth factor-beta regulates collagen gel contraction by increasing alpha 2 beta 1 integrin expression in osteogenic cells.
AuthorsRiikonen T, Koivisto L, Vihinen P, Heino J
JournalJ Biol Chem
PubMed ID7529233
'The contraction of floating collagen gels is suggested to mimic the reorganization of collagenous matrix during development and tissue healing. Here, we have studied two osteogenic cell lines, namely MG-63 and HOS, and a chemically transformed subclone of HOS cells, HOS-MNNG. Transforming growth factor-beta (TGF-beta), a putative regulator of bone ... More
The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells.
AuthorsZheng W, Flavell RA
JournalCell
PubMed ID9160750
'CD4 T cells potentiate the inflammatory or humoral immune response through the action of Th1 and Th2 cells, respectively. The molecular basis of the differentiation of these cells from naive T cell precursors is, however, unclear. We found that GATA-3 was selectively expressed in Th2 cells. GATA-3 is expressed at ... More
Phosphatidylinositol 3-kinase activity is required for hepatocyte growth factor-induced mitogenic signals in epithelial cells.
AuthorsRahimi N, Tremblay E, Elliott B
JournalJ Biol Chem
PubMed ID8798760
'Phosphatidylinositol (PI) 3-kinase is an important enzyme implicated in growth factor-stimulated intracellular signaling. In this study we have shown that hepatocyte growth factor (HGF) induces a rapid tyrosine phosphorylation of PI 3-kinase and association with HGF receptor/Met in Mv1Lu epithelial cells. Murine mammary carcinoma (SP1) cells, which co-express HGF and ... More
Methylation of histone H3 by COMPASS requires ubiquitination of histone H2B by Rad6.
Authors Dover Jim; Schneider Jessica; Tawiah-Boateng Mary Anne; Wood Adam; Dean Kimberly; Johnston Mark; Shilatifard Ali;
JournalJ Biol Chem
PubMed ID12070136
'The DNA of eukaryotes is wrapped around nucleosomes and packaged into chromatin. Covalent modifications of the histone proteins that comprise the nucleosome alter chromatin structure and have major effects on gene expression. Methylation of lysine 4 of histone H3 by COMPASS is required for silencing of genes located near chromosome ... More
Truncation of NH2-terminal amino acid residues increases agonistic potency of leukotactin-1 on CC chemokine receptors 1 and 3.
Authors Lee Jae Kwon; Lee Eun Hwa; Yun Yeo Pyo; Kim Kyungjae; Kwack KyuBum; Na Doe Sun; Kwon Byoung S; Lee Chong-Kil;
JournalJ Biol Chem
PubMed ID11832479
'Leukotactin-1 (Lkn-1) is a human CC chemokine that binds to both CC chemokine receptor 1 (CCR1) and CCR3. Structurally, Lkn-1 is distinct from other human CC chemokines in that it has long amino acid residues preceding the first cysteine at the NH(2) terminus, and contains two extra cysteines. NH(2)-terminal amino ... More
Celecoxib induces apoptosis by inhibiting 3-phosphoinositide-dependent protein kinase-1 activity in the human colon cancer HT-29 cell line.
'Nonsteroidal anti-inflammatory drugs, which inhibit cyclooxygenase (COX) activity, are powerful antineoplastic agents that exert their antiproliferative and proapoptotic effects on cancer cells by COX-dependent and/or COX-independent pathways. Celecoxib, a COX-2-specific inhibitor, has been shown to reduce the number of adenomatous colorectal polyps in patients with familial adenomatous polyposis. Here, we ... More
Mechanisms of desensitization and resensitization of proteinase-activated receptor-2.
Authors Böhm S K; Khitin L M; Grady E F; Aponte G; Payan D G; Bunnett N W;
JournalJ Biol Chem
PubMed ID8703006
'Proteinase-activated receptor-2 (PAR-2) is a G-protein-coupled receptor that is expressed by intestinal epithelial cells, which are episodically exposed to pancreatic trypsin in the intestinal lumen. Trypsin cleaves PAR-2 to expose a tethered ligand, which irreversibly activates the receptor. Thus, PAR-2 may desensitize and resensitize by novel mechanisms. We examined these ... More
Multicolor and electron microscopic imaging of connexin trafficking.
Authors Gaietta Guido; Deerinck Thomas J; Adams Stephen R; Bouwer James; Tour Oded; Laird Dale W; Sosinsky Gina E; Tsien Roger Y; Ellisman Mark H;
JournalScience
PubMed ID11964472
'Recombinant proteins containing tetracysteine tags can be successively labeled in living cells with different colors of biarsenical fluorophores so that older and younger protein molecules can be sharply distinguished by both fluorescence and electron microscopy. Here we used this approach to show that newly synthesized connexin43 was transported predominantly in ... More
Ectopic expression of retinoic acid early inducible-1 gene (RAE-1) permits natural killer cell-mediated rejection of a MHC class I-bearing tumor in vivo.
Authors Cerwenka A; Baron J L; Lanier L L;
JournalProc Natl Acad Sci U S A
PubMed ID11562472
In 1986, Kärre and colleagues reported that natural killer (NK) cells rejected an MHC class I-deficient tumor cell line (RMA-S) but they did not reject the same cell line if it expressed MHC class I (RMA). Based on this observation, they proposed the concept that NK cells provide immune surveillance ... 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
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
Requirement of the p130CAS-Crk coupling for metastasis suppressor KAI1/CD82-mediated inhibition of cell migration.
AuthorsZhang XA, He B, Zhou B, Liu L,
JournalJ Biol Chem
PubMed ID12738793
KAI1/CD82 protein is a member of the tetraspanin superfamily and has been rediscovered as a cancer metastasis suppressor. The mechanism of KAI1/CD82-mediated suppression of cancer metastasis remains to be established. In this study, we found that migration of the metastatic prostate cancer cell line Du145 was substantially inhibited when KAI1/CD82 ... 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 expression of Sprouty1, an inhibitor of fibroblast growth factor signal transduction, is decreased in human prostate cancer.
AuthorsKwabi-Addo B, Wang J, Erdem H, Vaid A, Castro P, Ayala G, Ittmann M,
JournalCancer Res
PubMed ID15256439
A considerable body of evidence indicates that alterations of fibroblast growth factors (FGFs) and their receptors contribute to prostate cancer progression. Recently, a new family of regulators of FGF activity has been identified. The Sprouty gene family negatively regulates FGF signaling in a variety of systems and could potentially limit ... More
Complementation of defective translesion synthesis and UV light sensitivity in xeroderma pigmentosum variant cells by human and mouse DNA polymerase eta.
AuthorsYamada A, Masutani C, Iwai S, Hanaoka F
JournalNucleic Acids Res
PubMed ID10871396
Defects in the human gene XPV result in the variant form of the genetic disease xeroderma pigmentosum (XP-V). XPV encodes DNA polymerase eta, a novel DNA polymerase that belongs to the UmuC/DinB/Rad30 superfamily. This polymerase catalyzes the efficient and accurate translesion synthesis of DNA past cis-syn cyclobutane di-thymine lesions. In ... More
A knock-out mouse model for methylmalonic aciduria resulting in neonatal lethality.
Methylmalonic aciduria is a human autosomal recessive disorder of organic acid metabolism resulting from a functional defect in the activity of the enzyme methylmalonyl-CoA mutase. Based upon the homology of the human mutase locus with the mouse locus, we have chosen to disrupt the mouse mutase locus within the critical ... More
T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with beta-catenin to coactivate C/EBPalpha and steroidogenic factor 1 transcription factors.
We have cloned T-cell factor 4N (TCF-4N), an alternative isoform of TCF-4, from developing pituitary and 3T3-L1 preadipocytes. This protein contains the N-terminal interaction domain for beta-catenin but lacks the DNA binding domain. While TCF-4N inhibited coactivation by beta-catenin of a TCF/lymphoid-enhancing factor (LEF)-dependent promoter, TCF-4N potentiated coactivation by beta-catenin ... More
alpha-Dystroglycan is a laminin receptor involved in extracellular matrix assembly on myotubes and muscle cell viability.
AuthorsMontanaro F, Lindenbaum M, Carbonetto S
JournalJ Cell Biol
PubMed ID10366602
alpha-Dystroglycan (alpha-DG) is a laminin-binding protein and member of a glycoprotein complex associated with dystrophin that has been implicated in the etiology of several muscular dystrophies. To study the function of DG, C2 myoblasts were transfected stably with an antisense DG expression construct. Myotubes from two resulting clones (11F and ... More
Regulation of integrin-mediated T cell adhesion by the transmembrane protein tyrosine phosphatase CD45.
AuthorsShenoi H, Seavitt J, Zheleznyak A, Thomas ML, Brown EJ
JournalJ Immunol
PubMed ID10358156
The transmembrane protein tyrosine phosphatase CD45 is required for Ag receptor signal transduction in lymphocytes. Recently, a role for CD45 in the regulation of macrophage adhesion has been demonstrated as well. To investigate further the role of CD45 in the regulation of adhesion, we examined integrin-mediated adhesion to fibronectin of ... More
Integrin alpha 2 beta 1 is a positive regulator of collagenase (MMP-1) and collagen alpha 1(I) gene expression.
AuthorsRiikonen T, Westermarck J, Koivisto L, Broberg A, Kähäri VM, Heino J
JournalJ Biol Chem
PubMed ID7768957
A classical model for studying the effects of extracellular matrix is to culture cells inside a three-dimensional collagen gel. When surrounded by fibrillar collagen, many cell types decrease the production of type I collagen, and the expression of interstitial collagenase (matrix metalloproteinase-1; MMP-1) is simultaneously induced. To study the role ... More
The human integrin alpha 8 beta 1 functions as a receptor for tenascin, fibronectin, and vitronectin.
AuthorsSchnapp LM, Hatch N, Ramos DM, Klimanskaya IV, Sheppard D, Pytela R
JournalJ Biol Chem
PubMed ID7559467
The integrin family of adhesion receptors consists of at least 21 heterodimeric transmembrane proteins that differ in their tissue distribution and ligand specificity. The recently identified alpha 8 integrin subunit associates with beta 1 and is predominantly expressed in smooth muscle and other contractile cells in adult tissues, and in ... More
Involvement of Egr-1/RelA synergy in distinguishing T cell activation from tumor necrosis factor-alpha-induced NF-kappa B1 transcription
AuthorsCogswell PC, Mayo MW, Baldwin AS Jr
JournalJ Exp Med
PubMed ID9053449
NF-kappa B is an important transcription factor required for T cell proliferation and other immunological functions. The NF-kappa B1 gene encodes a 105-kD protein that is the precursor of the p50 component of NF-kappa B. Previously, we and others have demonstrated that NF-kappa B regulates the NF-kappa B1 gene. In ... More
A new mouse gene, SRG3, related to the SWI3 of Saccharomyces cerevisiae, is required for apoptosis induced by glucocorticoids in a thymoma cell line.
AuthorsJeon SH, Kang MG, Kim YH, Jin YH, Lee C, Chung HY, Kwon H, Park SD, Seong RH,
JournalJ Exp Med
PubMed ID9151708
We isolated a new mouse gene that is highly expressed in thymocytes, testis, and brain. This gene, SRG3, showed a significant sequence homology to SWI3, a yeast transcriptional activator, and its human homolog BAF155. SRG3 encodes 1,100 amino acids and has 33-47% identity with SWI3 protein over three regions. The ... More
Human T helper cell differentiation is regulated by the combined action of cytokines and accessory cell-dependent costimulatory signals.
AuthorsPalmer EM, van Seventer GA
JournalJ Immunol
PubMed ID9058798
We have developed an in vitro differentiation model for human Th cells to study the role of cytokines and accessory cell-dependent costimulatory signals in this process. Peripheral blood-derived CD4+ naive (CD45RA+ RO-) T cells were stimulated in weekly intervals with immobilized anti-CD3 mAb, accessory cells, and exogenous cytokines, and were ... More
Envelope variants from women recently infected with clade A human immunodeficiency virus type 1 confer distinct phenotypes that are discerned by competition and neutralization experiments.
AuthorsPainter SL, Biek R, Holley DC, Poss M,
JournalJ Virol
PubMed ID12857914
Women infected with clade A human immunodeficiency virus type 1 harbor a virus population that is genetically diverse in the envelope gene, a fact that contrasts with the homogeneous virus population identified in newly infected men. It is not known whether viral genetic diversity at this early stage of infection ... More
Myocardin expression is regulated by nkx2.5, and its function is required for cardiomyogenesis.
AuthorsUeyama T, Kasahara H, Ishiwata T, Nie Q, Izumo S,
JournalMol Cell Biol
PubMed ID14645532
Nkx2.5 (also known as Csx) is an evolutionarily conserved cardiac transcription factor of the homeobox gene family. Nkx2.5 is required for early heart development, since Nkx2.5-null mice die before completion of cardiac looping. To identify genes regulated by Nkx2.5 in the developing heart, we performed subtractive hybridization by using RNA ... More
The presenilin 2 mutation (N141I) linked to familial Alzheimer disease (Volga German families) increases the secretion of amyloid beta protein ending at the 42nd (or 43rd) residue [see comments]
AuthorsTomita T, Maruyama K, Saido TC, Kume H, Shinozaki K, Tokuhiro S, Capell A, Walter J, Grunberg J, Haass C, Iwatsubo T, Obata K
JournalProc Natl Acad Sci U S A
PubMed ID9050898
To gain insights into the significance of presenilins (PS) in the pathogenetic mechanisms of early-onset familial Alzheimer disease (FAD), we expressed cDNAs for wild-type PS2 and PS2 with the Volga German (N141I) mutation in cultured cells and then examined the metabolism of the transfected proteins and their effect on the ... More
Identification of CCR8: a human monocyte and thymus receptor for the CC chemokine I-309
The human CC chemokine I-309 is a potent monocyte chemoattractant and inhibits apoptosis in thymic cell lines. Here, we identify a specific human I-309 receptor, and name it CCR8 according to an accepted nomenclature system. The receptor has seven predicted transmembrane domains, is expressed constitutively in monocytes and thymus, and ... More
Human CD4+ cells transfected with IL-16 cDNA are resistant to HIV-1 infection: inhibition of mRNA expression [see comments]
AuthorsZhou P, Goldstein S, Devadas K, Tewari D, Notkins AL
JournalNat Med
PubMed ID9176493
Interleukin-16 (IL-16) is secreted by activated CD8+ T lymphocytes and acts on CD4+ T lymphocytes, monocytes and eosinophils. Recently, the C- terminal 130-amino acid portion of IL-16 was shown to suppress HIV-1 replication in vitro. To explore the potential of human IL-16 for gene therapy, this portion was transfected into ... More
Mutagenesis of apobec-1, the catalytic subunit of the mammalian apolipoprotein B mRNA editing enzyme, reveals distinct domains that mediate cytosine nucleoside deaminase, RNA binding, and RNA editing activity.
AuthorsMacGinnitie AJ, Anant S, Davidson NO
JournalJ Biol Chem
PubMed ID7782343
Apolipoprotein (apo) B48 is synthesized by mammalian small intestine as a result of post-transcriptional RNA editing. This process is mediated by an enzyme complex containing a catalytic subunit, apobec-1, which is homologous to other cytidine deaminases, particularly in a domain (H/C)-(A/V)-E-(X)24-30-P-C-(X)2-C which coordinates zinc, apobec-1, expressed as a glutathione S-transferase ... More
The varicella-zoster virus immediate early protein, IE62, can positively regulate its cognate promoter.
AuthorsPerera LP, Mosca JD, Sadeghi-Zadeh M, Ruyechan WT, Hay J,
JournalVirology
PubMed ID1329324
Varicella-Zoster virus (VZV) is a neurotropic alphaherpes virus closely related to herpes simplex virus (HSV). However, unlike its close relative HSV, VZV lacks a functional alpha-TIF (alpha-gene transinducing factor) that activates the transcription of immediate early genes during the initial events of the virus life cycle. Hence, in the absence ... More
Formation of heteromeric gap junction channels by connexins 40 and 43 in vascular smooth muscle cells.
AuthorsHe DS, Jiang JX, Taffet SM, Burt JM
JournalProc Natl Acad Sci U S A
PubMed ID10339616
Connexin (Cx) 43 and Cx40 are coexpressed in several tissues, including cardiac atrial and ventricular myocytes and vascular smooth muscle. It has been shown that these Cxs form homomeric/homotypic channels with distinct permeability and gating properties but do not form functional homomeric/heterotypic channels. If these Cxs were to form heteromeric ... More
Discrimination between RelA and RelB transcriptional regulation by a dominant negative mutant of IkappaBalpha.
AuthorsFerreira V, Tarantino N, Korner M
JournalJ Biol Chem
PubMed ID9417120
RelA and RelB belong to the nuclear factor-kappaB (NF-kappaB-Rel) transcription factor family. Both proteins are structurally and functionally related, but their intracellular and tissue distributions are different. In resting cells, RelB is found mostly in the nucleus, whereas RelA is sequestered in the cytosol by protein inhibitors, among which IkappaBalpha ... More
Targeting of HIV-1 antigens for rapid intracellular degradation enhances cytotoxic T lymphocyte (CTL) recognition and the induction of de novo CTL responses in vivo after immunization.
AuthorsTobery TW, Siliciano RF
JournalJ Exp Med
PubMed ID9120397
CD8+ cytotoxic T lymphocytes (CTLs) have the ability to recognize and eliminate virally infected cells before new virions are produced within that cell. Therefore, a rapid and vigorous CD8+ CTL response, induced by vaccination, can, in principle, prevent disseminated infection in vaccinated individuals who are exposed to the relevant virus. ... More
Human macrophage-derived chemokine (MDC), a novel chemoattractant for monocytes, monocyte-derived dendritic cells, and natural killer cells.
A cDNA encoding a novel human chemokine was isolated by random sequencing of cDNA clones from human monocyte-derived macrophages. This protein has been termed macrophage-derived chemokine (MDC) because it appears to be synthesized specifically by cells of the macrophage lineage. MDC has the four-cysteine motif and other highly conserved residues ... More
Modulation of cardiac Na+ channels expressed in a mammalian cell line and in ventricular myocytes by protein kinase C.
AuthorsQu Y, Rogers J, Tanada T, Scheuer T, Catterall WA
JournalProc Natl Acad Sci U S A
PubMed ID8159741
Cardiac rH1 Na+ channel alpha subunits were expressed in cells of the Chinese hamster lung 1610 cell line by transfection, and a stable cell line expressing cardiac Na+ channels (SNa-rH1) was isolated. Mean Na+ currents of 2.2 +/- 1.0 nA were recorded, which corresponds to a cell surface density of ... More
The p85 regulatory subunit controls sequential activation of phosphoinositide 3-kinase by Tyr kinases and Ras.
AuthorsJimenez C, Hernandez C, Pimentel B, Carrera AC,
JournalJ Biol Chem
PubMed ID12196526
Class IA phosphoinositide 3-kinase (PI3K) is a heterodimer composed of a p85 regulatory and a p110 catalytic subunit that regulates a variety of cell responses, including cell division and survival. PI3K is activated following Tyr kinase stimulation and by Ras. We found that the C-terminal region of p85, including the ... More
Suppression of growth of renal carcinoma cells by the von Hippel-Lindau tumor suppressor gene.
Clear cell renal carcinomas are most frequently characterized by loss of function of both copies of the von Hippel-Lindau (VHL) disease gene, suggesting that the VHL gene product plays an important role in regulating renal cell proliferation. To directly assess the function of the VHL gene product, we transfected the ... More
beta-Thymosins are not simple actin monomer buffering proteins. Insights from overexpression studies.
AuthorsSun HQ, Kwiatkowska K, Yin HL
JournalJ Biol Chem
PubMed ID8621581
beta-Thymosins are the currently favored candidates for maintaining the large actin monomer (G-actin) pool in living cells. To determine if beta-thymosin behaves like a simple G-actin buffering agent in the complex environment of a cell, we overexpressed thymosin beta10 (Tbeta 10) in NIH3T3 cells and determined the effect on the ... More
The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial-mesenchymal transition.
AuthorsSavagner P, Yamada KM, Thiery JP
JournalJ Cell Biol
PubMed ID9182671
Epithelial-mesenchymal transition (EMT) is an essential morphogenetic process during embryonic development. It can be induced in vitro by hepatocyte growth factor/scatter factor (HGF/SF), or by FGF-1 in our NBT-II cell model for EMT. We tested for a central role in EMT of a zinc-finger protein called Slug. Slug mRNA and ... More
The HIV-1 nef protein interferes with phosphatidylinositol 3-kinase activation 1.
AuthorsGraziani A, Galimi F, Medico E, Cottone E, Gramaglia D, Boccaccio C, Comoglio PM
JournalJ Biol Chem
PubMed ID8636073
nef is a human immunodeficiency virus (HIV) gene encoding a 27-kDa myristoylated protein with structural features of a signal transducing molecule, but whose functions are largely unknown. We studied the interactions of Nef with the signal transduction pathways triggered by the platelet-derived growth factor (PDGF) receptor. The association of phosphatidylinositol ... More
Molecular cloning and characterization of a novel 3'-phosphoadenosine 5'-phosphosulfate transporter, PAPST2.
AuthorsKamiyama S, Sasaki N, Goda E, Ui-Tei K, Saigo K, Narimatsu H, Jigami Y, Kannagi R, Irimura T, Nishihara S,
JournalJ Biol Chem
PubMed ID16492677
Sulfation is an important posttranslational modification associated with a variety of molecules. It requires the involvement of the high energy form of the universal sulfate donor, 3'-phosphoadenosine 5'-phosphosulfate (PAPS). Recently, we identified a PAPS transporter gene in both humans and Drosophila. Although human colonic epithelial tissues express many sulfated glycoconjugates, ... More
The UL12.5 gene product of herpes simplex virus type 1 exhibits nuclease and strand exchange activities but does not localize to the nucleus.
AuthorsReuven NB, Antoku S, Weller SK,
JournalJ Virol
PubMed ID15078942
The herpes simplex virus type 1 (HSV-1) alkaline nuclease, encoded by the UL12 gene, plays an important role in HSV-1 replication, as a null mutant of UL12 displays a severe growth defect. Although the precise in vivo role of UL12 has not yet been determined, several in vitro activities have ... 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
A novel tetracycline-dependent transactivator with E2F4 transcriptional activation domain.
A tetracycline-controlled gene expression system provides a powerful tool to dissect the functions of gene products. However, it often appears difficult to establish cell lines or transgenic animals stably expressing tetracycline-dependent transactivators, possibly as a result of toxicity of the transactivator domains used. In order to overcome this problem, we ... More
Underediting of glutamate receptor GluR-B mRNA in malignant gliomas.
Authors Maas S; Patt S; Schrey M; Rich A;
JournalProc Natl Acad Sci U S A
PubMed ID11717408
In mammals, RNA editing by site-selective adenosine deamination regulates key functional properties of neurotransmitter receptors in the central nervous system. Glutamate receptor subunit B is nearly 100% edited at one position (the Q/R-site), which is essential for normal receptor function. Its significance is apparent from mouse models in which a ... More
Functional analysis of the human D2 dopamine receptor missense variants.
Authors Cravchik A; Sibley D R; Gejman P V;
JournalJ Biol Chem
PubMed ID8824240
The human dopamine D2 receptor gene (DRD2) has three polymorphic variants that predict the amino acid substitutions Val96 --> Ala, Pro310 --> Ser, and Ser311 --> Cys in the receptor protein. We have investigated the ligand binding and signal transduction properties of these human D2 receptor variants by stably expressing ... More
Requirement of tyrosine residues 333 and 338 of the growth hormone (GH) receptor for selected GH-stimulated function.
We have examined the involvement of tyrosine residues 333 and 338 of the growth hormone (GH) receptor in the cellular response to GH. Stable Chinese hamster ovary (CHO) cell clones expressing a receptor with tyrosine residues at position 333 and 338 of the receptor substituted for phenylalanine (CHO-GHR1-638 Y333F, Y338F) ... More
The role of Tyr13 and Lys15 of interleukin-8 in the high affinity interaction with the interleukin-8 receptor type A.
Authors Schraufstätter I U; Ma M; Oades Z G; Barritt D S; Cochrane C G;
JournalJ Biol Chem
PubMed ID7737976
Interleukin-8 (IL-8) has at least two binding regions for both the A and the B type IL-8 receptors. This study defines an important region between Cys7 and Cys50 that, together with the Glu4-Leu5-Arg6 sequence of the NH2 terminus, accounts for the high affinity binding of IL-8 to the IL-8 A ... More
TRAIL-induced apoptosis requires Bax-dependent mitochondrial release of Smac/DIABLO.
Authors Deng Yibin; Lin Yahong; Wu Xiangwei;
JournalGenes Dev
PubMed ID11782443
Recent reports suggest that a cross-talk exists between apoptosis pathways mediated by mitochondria and cell death receptors. In the present study, we report that mitochondrial events are required for apoptosis induced by the cell death ligand TRAIL (TNF-related apoptosis-inducing ligand) in human cancer cells. We show that the Bax null ... More
Rig is a novel Ras-related protein and potential neural tumor suppressor.
Authors Ellis Chad A; Vos Michele D; Howell Heather; Vallecorsa Teresa; Fults Daniel W; Clark Geoffrey J;
JournalProc Natl Acad Sci U S A
PubMed ID12107278
The Ras superfamily consists of a large group of monomeric GTPases demonstrating homology to Ras oncoproteins. Although structurally similar, Ras-superfamily proteins are functionally diverse. Whereas some members exhibit oncogenic properties, others may serve as tumor suppressors. We have identified a novel Ras-related protein that suppresses cell growth and have designated ... More
Interleukin-22 (IL-22) activates the JAK/STAT, ERK, JNK, and p38 MAP kinase pathways in a rat hepatoma cell line. Pathways that are shared with and distinct from IL-10.
IL (interleukin)-22 is an IL-10-related cytokine; its main biological activity known thus far is the induction of acute phase reactants in liver and pancreas. IL-22 signals through a receptor that is composed of two chains from the class II cytokine receptor family: IL-22R (also called ZcytoR11/CRF2-9) and IL-10Rbeta (CRF2-4), which ... More
The first proline of PALP motif at the C terminus of presenilins is obligatory for stabilization, complex formation, and gamma-secretase activities of presenilins.
Mutations in presenilin (PS) genes cause early-onset familial Alzheimer's disease by increasing production of the amyloidogenic form of amyloid beta peptides ending at residue 42 (Abeta42). PS is an evolutionarily conserved multipass transmembrane protein, and all known PS proteins contain a proline-alanine-leucine-proline (PALP) motif starting at proline (P) 414 (amino ... More
A somatic cell genetic system for dissecting hemopoietic cytokine signal transduction.
Somatic cell genetics has proven to be a powerful tool for the dissection of cytokine signal transduction pathways. Here we describe a system in which interleukin-6 (IL-6) signaling may be dissected using myeloid leukemic M1 cells. We utilized two properties of M1 cell differentiation to isolate IL-6-unresponsive mutants. First, M1 ... More
Multidrug-resistant human sarcoma cells with a mutant P-glycoprotein, altered phenotype, and resistance to cyclosporins.
A variant of the multidrug-resistant human sarcoma cell line Dx5 was derived by co-selection with doxorubicin and the cyclosporin D analogue PSC 833, a potent inhibitor of the multidrug transporter P-glycoprotein. The variant DxP cells manifest an altered phenotype compared with Dx5, with decreased cross-resistance to Vinca alkaloids and no ... More
Molecular basis for the dichotomy in Plasmodium falciparum adhesion to CD36 and chondroitin sulfate A.
Authors Gamain Benoit; Gratepanche Sylvie; Miller Louis H; Baruch Dror I;
JournalProc Natl Acad Sci U S A
PubMed ID12096191
Plasmodium falciparum-infected erythrocytes adhere dichotomously to the host receptors CD36 and chondroitin sulfate A (CSA). This dichotomy is associated with parasite sequestration to microvasculature beds (CD36) or placenta (CSA), leading to site-specific pathogenesis. Both properties are mediated by members of the variant P. falciparum erythrocyte membrane protein 1 (PfEMP-1) family ... 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
Processing site blockade results in more efficient conversion of proenkephalin to active opioid peptides.
Authors Johanning K; Mathis J P; Lindberg I;
JournalJ Biol Chem
PubMed ID8910386
Prohormones are known to be processed at various cleavage sites in a defined temporal order, suggesting the possibility of sequential unfolding of processing sites. In order to investigate whether sequential processing at predefined sites is in fact required for proper processing, site-directed mutagenesis was performed to block known initial cleavage ... More
Regulation of alternative splicing of protein kinase C beta by insulin.
Authors Chalfant C E; Mischak H; Watson J E; Winkler B C; Goodnight J; Farese R V; Cooper D R;
JournalJ Biol Chem
PubMed ID7768933
Insulin regulates a diverse array of cellular signaling processes involved in the control of growth, differentiation, and cellular metabolism. Insulin increases glucose transport via a protein kinase C (PKC)-dependent pathway in BC3H-1 myocytes, but the function of specific PKC isozymes in insulin action has not been elucidated. Two isoforms of ... More
Increased expression of dihydrodiol dehydrogenase induces resistance to cisplatin in human ovarian carcinoma cells.
Authors Deng Hong Bing; Parekh Hemant K; Chow K-C; Simpkins Henry;
JournalJ Biol Chem
PubMed ID11842089
We employed cDNA microarrays to identify the differentially expressed genes in a cisplatin-sensitive parental (2008) human ovarian carcinoma cell line and its cisplatin-resistant variant (2008/C13*). Differential expression of five genes was found in the 2008/C13* cells, a result confirmed by semi-quantitative reverse transcription-PCR. The five genes were identified as fibroblast ... More
Influence of second and third cytoplasmic loops on binding, internalization, and coupling of chimeric bombesin/m3 muscarinic receptors.
Authors Tseng M J; Coon S; Stuenkel E; Struk V; Logsdon C D;
JournalJ Biol Chem
PubMed ID7629092
In order to investigate the molecular basis for differences in the characteristics of bombesin (Bn) and m3 muscarinic cholinergic (m3 ACh) receptors, chimeric Bn receptors possessing cytoplasmic domains from the m3 ACh receptor were produced. The receptors were expressed in CHO-K1 cells and binding, structural, and signal transduction characteristics were ... More
High glucose stimulates synthesis of fibronectin via a novel protein kinase C, Rap1b, and B-Raf signaling pathway.
Authors Lin Sun; Sahai Atul; Chugh Sumant S; Pan Xiaomin; Wallner Elisabeth I; Danesh Farhad R; Lomasney Jon W; Kanwar Yashpal S;
JournalJ Biol Chem
PubMed ID12196513
The molecular mechanism(s) by which high glucose induces fibronectin expression via G-protein activation in the kidney are largely unknown. This investigation describes the effect of high glucose (HG) on a small GTP-binding protein, Rap1b, expression and activation, and the relevance of protein kinase C (PKC) and Raf pathways in fibronectin ... More
Reactive oxygen species as downstream mediators of angiogenic signaling by vascular endothelial growth factor receptor-2/KDR.
Recent evidence shows the involvement of reactive oxygen species (ROS) in the mitogenic cascade initiated by the tyrosine kinase receptors of several growth factor peptides. We have asked whether also the vascular endothelial growth factor (VEGF) utilizes ROS as messenger intermediates downstream of the VEGF receptor-2 (VEGFR-2)/KDR receptor given that ... More
Intracellular activation of human adamalysin 19/disintegrin and metalloproteinase 19 by furin occurs via one of the two consecutive recognition sites.
Authors Kang Tiebang; Zhao Yun-Ge; Pei Duanqing; Sucic Joseph F; Sang Qing-Xiang Amy;
JournalJ Biol Chem
PubMed ID12006600
Adamalysin 19 (a disintegrin and metalloproteinase 19, ADAM19, or meltrin beta) is a plasma membrane metalloproteinase. Human ADAM19 zymogen contains two potential furin recognition sites (RX(K/R)R), (196)KRPR(200)R and (199)RRMK(203)R, between its pro- and catalytic domains. Protein N-terminal sequencing revealed that the cellular mature forms of hADAM19 started at (204)EDLNSMK, demonstrating ... More
Prioritization of cancer therapeutic targets using CRISPR-Cas9 screens.
AuthorsBehan FM, Iorio F, Picco G, Gonçalves E, Beaver CM, Migliardi G, Santos R, Rao Y, Sassi F, Pinnelli M, Ansari R, Harper S, Jackson DA, McRae R, Pooley R, Wilkinson P, van der Meer D, Dow D, Buser-Doepner C, Bertotti A, Trusolino L, Stronach EA, Saez-Rodriguez J, Yusa K, Garnett MJ
JournalNature
PubMed ID30971826
'Functional genomics approaches can overcome limitations-such as the lack of identification of robust targets and poor clinical efficacy-that hamper cancer drug development. Here we performed genome-scale CRISPR-Cas9 screens in 324 human cancer cell lines from 30 cancer types and developed a data-driven framework to prioritize candidates for cancer therapeutics. We integrated cell ... More
The FZD7-TWIST1 axis is responsible for anoikis resistance and tumorigenesis in ovarian carcinoma.
AuthorsTan M, Asad M, Heong V, Wong MK, Tan TZ, Ye J, Kuay KT, Thiery JP, Scott C, Huang RY
JournalMol Oncol
PubMed ID30548372
Frizzled family receptor 7 (FZD7), a Wnt signaling receptor, is associated with the maintenance of stem cell properties and cancer progression. FZD7 has emerged as a potential therapeutic target because it is capable of transducing both canonical and noncanonical Wnt signals. In this study, we investigated the regulatory pathway downstream ... More
Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion.
AuthorsSu R, Dong L, Li Y, Gao M, Han L, Wunderlich M, Deng X, Li H, Huang Y, Gao L, Li C, Zhao Z, Robinson S, Tan B, Qing Y, Qin X, Prince E, Xie J, Qin H, Li W, Shen C, Sun J, Kulkarni P, Weng H, Huang H, Chen Z, Zhang B, Wu X, Olsen MJ, Müschen M, Marcucci G, Salgia R, Li L, Fathi AT, Li Z, Mulloy JC, Wei M, Horne D, Chen J
JournalCancer Cell
PubMed ID32531268
Fat mass and obesity-associated protein (FTO), an RNA N