Isolation and characterization of a novel cDNA encoding a human UDP-glucuronosyltransferase active on C19 steroids.
AuthorsBeaulieu M,Lévesque E,Hum DW,Bélanger A
JournalThe Journal of biological chemistry
PubMed ID8798464
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
Molecular cloning and functional expression of murine JE (monocyte chemoattractant protein 1) and murine macrophage inflammatory protein 1alpha receptors: evidence for two closely linked C-C chemokine receptors on chromosome 9.
Authors Boring L; Gosling J; Monteclaro F S; Lusis A J; Tsou C L; Charo I F;
JournalJ Biol Chem
PubMed ID8631787
'We have isolated cDNA clones that encode two closely related, murine C-C chemokine receptors. Both receptors are members of the G-protein-coupled, seven-transmembrane domain family of receptors and are most closely related to the human monocyte chemoattractant protein 1 receptor. Expression of each of the receptors was detected in murine monocyte/macrophage ... 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
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
Interaction between the components of the interferon gamma receptor complex.
AuthorsSerguei V. Kotenko , Lara S. Izotova , Brian P. Pollack , Thomas M. Mariano , Robert J. Donnelly , Geetha Muthukumaran , Jeffry R. Cook , Gianni Garotta, Olli Silvennoinen, James N. Ihle, Sidney Pestka
JournalJ Biol Chem
PubMed ID7673114
'Interferon gamma (IFN-gamma) signals through a multimeric receptor complex consisting of two different chains: the IFN-gamma receptor binding subunit (IFN-gamma R, IFN-gamma R1), and a transmembrane accessory factor (AF-1, IFN-gamma R2) necessary for signal transduction. Using cell lines expressing different cloned components of the IFN-gamma receptor complex, we examined the ... 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
Smad4/DPC4-dependent Regulation of Biglycan Gene Expression by Transforming Growth Factor-beta in Pancreatic Tumor Cells.
'Overexpression of the small leucine-rich proteoglycan biglycan (BGN) in fibrosis and desmoplasia results from enhanced activity of transforming growth factor-beta (TGF-beta). In pancreatic adenocarcinoma, the tumor cells themselves may contribute to BGN synthesis in vivo, since 8 of 18 different pancreatic carcinoma cell lines constitutively expressed BGN mRNA, as shown ... 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
The proto-oncogene product c-Crk associates with insulin receptor substrate-1 and 4PS. Modulation by insulin growth factor-I (IGF) and enhanced IGF-I signaling.
Authors Beitner-Johnson D; Blakesley V A; Shen-Orr Z; Jimenez M; Stannard B; Wang L M; Pierce J; LeRoith D;
JournalJ Biol Chem
PubMed ID8621590
'The Crk proto-oncogene product is an SH2 and SH3 domain-containing adaptor protein which we have previously shown to become rapidly tyrosine phosphorylated in response to stimulation with insulin-like growth factor I (IGF-I) in NIH-3T3 cells. In order to further characterize the role of Crk in the IGF-I signaling pathway, NIH-3T3 ... More
Analysis of the hormone-dependent regulation of a JunD-estrogen receptor chimera.
Authors Francis M K; Phinney D G; Ryder K;
JournalJ Biol Chem
PubMed ID7744790
'The modular ligand-binding domains of steroid receptors have been widely used to generate protein chimeras that are ligand dependent for activity. In a similar manner, we generated a series of conditionally active JunD and c-Fos proteins by fusing their carboxyl (COOH)-terminal ends with a COOH-terminal fragment of the human estrogen ... More
CD36 is palmitoylated on both N- and C-terminal cytoplasmic tails.
Authors Tao N; Wagner S J; Lublin D M;
JournalJ Biol Chem
PubMed ID8798390
'The membrane protein CD36 has been reported to carry out a wide range of potential functions, including serving as a receptor for thrombospondin, collagen, oxidized low density lipoprotein, fatty acids, anionic phospholipids, and Plasmodium falciparum malaria parasitized erythrocytes. This implicates CD36 in cellular adhesion, human atherosclerotic lesion formation, lipid metabolism, ... More
The carboxyl terminus of GLUT4 contains a serine-leucine-leucine sequence that functions as a potent internalization motif in Chinese hamster ovary cells.
Authors Garippa R J; Johnson A; Park J; Petrush R L; McGraw T E;
JournalJ Biol Chem
PubMed ID8702815
'To characterize the trafficking motifs contained in the carboxyl terminus of GLUT4, a chimera (GTCTR) was constructed in which the carboxyl-terminal 30 amino acids of GLUT4 were substituted for the amino-terminal cytoplasmic domain of the transferrin receptor (TR). The endocytic behavior of this chimera was characterized in Chinese hamster ovary ... More
Activation and inhibition of G protein-coupled inwardly rectifying potassium (Kir3) channels by G protein beta gamma subunits.
AuthorsLei Q, Jones MB, Talley EM, Schrier AD, McIntire WE, Garrison JC, Bayliss DA
JournalProc Natl Acad Sci U S A
PubMed ID10944236
'G protein-coupled inwardly rectifying potassium (GIRK) channels can be activated or inhibited by different classes of receptors, suggesting a role for G proteins in determining signaling specificity. Because G protein betagamma subunits containing either beta1 or beta2 with multiple Ggamma subunits activate GIRK channels, we hypothesized that specificity might be ... More
Ubiquitination-independent Trafficking of G Protein-coupled Receptors to Lysosomes.
Authors Tanowitz Michael; Von Zastrow Mark;
JournalJ Biol Chem
PubMed ID12401797
'Ubiquitination of cytoplasmic lysine residues can target G protein-coupled receptors (GPCRs) to proteasomes and has recently been shown to also be required for sorting of certain GPCRs to lysosomes following ligand-induced endocytosis. We addressed the generality of this mechanism by examining regulated proteolysis of the murine delta opioid receptor (DOR) ... 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
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
Identification of the proteoglycan binding site in apolipoprotein B48.
'An initial event in atherosclerosis is the retention of lipoproteins within the intima of the vessel wall. Previously we identified Site B (residues 3359-3369) in apolipoprotein (apo) B100 as the proteoglycan binding sequence in low density lipoproteins (LDLs) and showed that the atherogenicity of apoB-containing lipoproteins is linked to their ... More
Signal transduction and ligand specificity of the human monocyte chemoattractant protein-1 receptor in transfected embryonic kidney cells.
Authors Myers S J; Wong L M; Charo I F;
JournalJ Biol Chem
PubMed ID7890708
'We have examined the ligand specificity and signal transduction pathways of a recently cloned receptor for monocyte chemoattractant protein-1 (MCP-1). In human 293 cells stably transfected with the MCP-1 receptor, MCP-1 bound specifically with high affinity (Kd = 260 pM) and induced a rapid mobilization of calcium from intracellular stores. ... 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
Stat3-Mediated Transformation of NIH-3T3 Cells by the Constitutively Active Q205L Go Protein
AuthorsRam PT, Horvath CM, Iyengar R
JournalScience
PubMed ID10615050
Expression of Q205L Galphao (Galphao*), an alpha subunit of heterotrimeric guanine nucleotide-binding proteins (G proteins) that lacks guanosine triphosphatase (GTPase) activity in NIH-3T3 cells, results in transformation. Expression of Galphao* in NIH-3T3 cells activated signal transducer and activator of transcription 3 (Stat3) but not mitogen-activated protein (MAP) kinases 1 or ... 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
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
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
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
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
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
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
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
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
Two splice variants of a tyrosine phosphatase differ in substrate specificity, DNA binding, and subcellular location.
Four different forms of a non-receptor type protein-tyrosine phosphatase are generated by alternative splicing; two of these forms (PTP-S2 and PTP-S4) are major forms, which are expressed in rat as well as human cells. Here we report that PTP-S2 binds to nonspecific DNA in vitro and localizes in the nucleus ... More
Basal transcription of the mouse sarco(endo)plasmic reticulum Ca2+-ATPase type 3 gene in endothelial cells is controlled by Ets-1 and Sp1.
AuthorsHadri L, Ozog A, Soncin F, Lompre AM
JournalJ Biol Chem
PubMed ID12119294
We reported previously that the sarco(endo)plasmic reticulum Ca(2+)-ATPase type 3 (SERCA3) gene is expressed in many tissues and in a subset of cells such as endothelial, epithelial, and lymphoid lineages. Here we analyzed the mechanisms involved in the regulation of transcription of the SERCA3 gene in endothelial cells. The promoter ... More
Hypoxia and Nitric Oxide Treatment Confer Tolerance to Glucose Starvation in a 5'-AMP-activated Protein Kinase-dependent Manner.
Hypoxia is a critical event for higher organisms, and cells and tissues react by increasing the oxygen supply by vasodilatation, angiogenesis, and erythropoiesis and maintaining cellular energy by increasing glycolysis and inhibiting anabolic pathways. Stimulation of glycolysis has been regarded as the main response that increases energy production during hypoxia; ... 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
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
A Cyclic AMP-dependent Pathway Regulates the Expression of Acetylcholinesterase during Myogenic Differentiation of C2C12 Cells.
Authors Siow Nina L; Choi Roy C Y; Cheng Anthony W M; Jiang Joy X S; Wan David C C; Zhu Shang Q; Tsim Karl W K;
JournalJ Biol Chem
PubMed ID12140295
The expression of acetylcholinesterase (AChE) is markedly increased during myogenic differentiation of C2C12 myoblasts to myotubes; the expression is mediated by intrinsic factor(s) during muscle differentiation. In order to analyze the molecular mechanisms regulating AChE expression during myogenic differentiation, a approximately 2.2-kb human AChE promoter tagged with a luciferase reporter ... More
Novel pathways associated with bypassing cellular senescence in human prostate epithelial cells.
Authors Schwarze Steven R; DePrimo Samuel E; Grabert Lisa M; Fu Vivian X; Brooks James D; Jarrard David F;
JournalJ Biol Chem
PubMed ID11836256
Cellular senescence forms a barrier that inhibits the acquisition of an immortal phenotype, a critical feature in tumorigenesis. The inactivation of multiple pathways that positively regulate senescence are required for immortalization. To identify these pathways in an unbiased manner, we performed DNA microarray analyses to assess the expression of 20,000 ... 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
The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel.
Authors Gee N S; Brown J P; Dissanayake V U; Offord J; Thurlow R; Woodruff G N;
JournalJ Biol Chem
PubMed ID8621444
Gabapentin (1-(aminomethyl)cyclohexane acetic acid; Neurontin) is a novel anticonvulsant drug, with a mechanism of action apparently dissimilar to that of other antiepileptic agents. We report here the isolation and characterization of a [3H]gabapentin-binding protein from pig cerebral cortex membranes. The detergent-solubilized binding protein was purified 1022-fold, in a six-step column-chromatographic ... More
The Selective Regulation of alpha Vbeta 1 Integrin Expression Is Based on the Hierarchical Formation of alpha V-containing Heterodimers.
Authors Koistinen Pekka; Heino Jyrki;
JournalJ Biol Chem
PubMed ID11997396
The integrin beta(1) subunit can form a heterodimer with 12 different alpha subunits. According to the present model, the expression level of any alphabeta complex is regulated by the availability of the specific alpha subunit, whereas beta(1) subunit is constantly present in a large excess. The expression of several heterodimers ... 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
The Tetraspan Protein Epithelial Membrane Protein-2 Interacts with beta 1 Integrins and Regulates Adhesion.
The growth arrest-specific-3 (GAS3)/PMP22 proteins are members of the four-transmembrane (tetraspan) superfamily. Although the function of these proteins is poorly understood, GAS3/PMP22 proteins have been implicated in the control of growth and progression of certain cancers. Epithelial membrane protein-2 (EMP2), a GAS3/PMP22 family member, was recently identified as a putative ... More
Optimization of tetracycline-responsive recombinant protein production and effect on cell growth and ER stress in mammalian cells.
The inducible T-REx system and other inducible expression systems have been developed in order to control the expression levels of recombinant protein in mammalian cells. In order to study the effects of heterologous protein expression on mammalian host behavior, the gene for recombinant Human transferrin (hTf) was integrated into HEK-293 ... More
The Death Domain of NF-kappa B1 p105 Is Essential for Signal-induced p105 Proteolysis.
Authors Beinke Soren; Belich Monica P; Ley Steven C;
JournalJ Biol Chem
PubMed ID11976329
Stimulation of cells with tumor necrosis factor alpha (TNFalpha) triggers NF-kappaB1 p105 proteolysis, releasing associated Rel subunits to translocate into the nucleus and modulate target gene expression. Phosphorylation of serine 927 within the p105 PEST region by the IkappaB kinase (IKK) complex is required to promote p105 proteolysis in response ... More
Structural elements that direct specific processing of different mammalian subtilisin-like prohormone convertases.
Authors Zhou A; Paquet L; Mains R E;
JournalJ Biol Chem
PubMed ID7665562
PC1 and PC2 are two important subtilisin-like prohormone convertases (PC) that undergo differential endoproteolytic processing steps and sequentially mediate proopiomelanocortin (POMC) processing. To investigate the structural elements directing the processing of different PCs, we constructed a series of mutant and chimeric PC proteins and expressed them in cell lines with ... More
Sensitivity of opioid receptor-like receptor ORL1 for chemical modification on nociceptin, a naturally occurring nociceptive peptide.
Nociceptin or orphanin FQ is a novel neuropeptide that activates an opioid-like G protein-coupled receptor ORL1. This heptadecapeptide FGGFTGARKSARKLANQ resembles kappa-opioid peptide dynorphin A but exhibits an opposite effect to make animals hyperreactive to nociceptive stimulations (Meunier, J.-C., Mollereau, C., Toll, L., Suaudeau, C., Moisand, C., Alvinerie, P., Butour, J.-L., ... More
The amino-terminal extracellular domain of the MCP-1 receptor, but not the RANTES/MIP-1alpha receptor, confers chemokine selectivity. Evidence for a two-step mechanism for MCP-1 receptor activation.
Authors Monteclaro F S; Charo I F;
JournalJ Biol Chem
PubMed ID8702581
The chemoattractant cytokines, MCP-1 (monocyte chemoattractant protein) and MIP-1alpha (macrophage inflammatory protein), are recognized by highly homologous but distinct receptors. To identify receptor domains involved in determining ligand specificity, we created a series of chimeric MCP-1 and RANTES (regulated on activation, normal T cell expressed and secreted)/MIP-1alpha receptors that progressively ... More
Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids.
AuthorsDijkstra KK, Cattaneo CM, Weeber F, Chalabi M, van de Haar J, Fanchi LF, Slagter M, van der Velden DL, Kaing S, Kelderman S, van Rooij N, van Leerdam ME, Depla A, Smit EF, Hartemink KJ, de Groot R, Wolkers MC, Sachs N, Snaebjornsson P, Monkhorst K, Haanen J, Clevers H, Schumacher TN, Voest EE
JournalCell
PubMed ID30100188
'Cancer immunotherapies have shown substantial clinical activity for a subset of patients with epithelial cancers. Still, technological platforms to study cancer T-cell interactions for individual patients and understand determinants of responsiveness are presently lacking. Here, we establish and validate a platform to induce and analyze tumor-specific T cell responses to epithelial ... More
A sequential EMT-MET mechanism drives the differentiation of human embryonic stem cells towards hepatocytes.
AuthorsLi Q, Hutchins AP, Chen Y, Li S, Shan Y, Liao B, Zheng D, Shi X, Li Y, Chan WY, Pan G, Wei S, Shu X, Pei D
JournalNat Commun
PubMed ID28466868
Reprogramming has been shown to involve EMT-MET; however, its role in cell differentiation is unclear. We report here that in vitro differentiation of hESCs to hepatic lineage undergoes a sequential EMT-MET with an obligatory intermediate mesenchymal phase. Gene expression analysis reveals that Activin A-induced formation of definitive endoderm (DE) accompanies ... More
Phosphoproteome-based kinase activity profiling reveals the critical role of MAP2K2 and PLK1 in neuronal autophagy.
AuthorsChen LL, Wang YB, Song JX, Deng WK, Lu JH, Ma LL, Yang CB, Li M, Xue Y
JournalAutophagy
PubMed ID28933595
Recent studies have demonstrated that dysregulation of macroautophagy/autophagy may play a central role in the pathogenesis of neurodegenerative disorders, and the induction of autophagy protects against the toxic insults of aggregate-prone proteins by enhancing their clearance. Thus, autophagy has become a promising therapeutic target against neurodegenerative diseases. In this study, ... More
LKB1, Salt-Inducible Kinases, and MEF2C Are Linked Dependencies in Acute Myeloid Leukemia.
AuthorsTarumoto Y, Lu B, Somerville TDD, Huang YH, Milazzo JP, Wu XS, Klingbeil O, El Demerdash O, Shi J, Vakoc CR
JournalMol Cell
PubMed ID29526696
The lineage-specific transcription factor (TF) MEF2C is often deregulated in leukemia. However, strategies to target this TF have yet to be identified. Here, we used a domain-focused CRISPR screen to reveal an essential role for LKB1 and its Salt-Inducible Kinase effectors (SIK3, in a partially redundant manner with SIK2) to ... More
Atlas of Circadian Metabolism Reveals System-wide Coordination and Communication between Clocks.
AuthorsDyar KA, Lutter D, Artati A, Ceglia NJ, Liu Y, Armenta D, Jastroch M, Schneider S, de Mateo S, Cervantes M, Abbondante S, Tognini P, Orozco-Solis R, Kinouchi K, Wang C, Swerdloff R, Nadeef S, Masri S, Magistretti P, Orlando V, Borrelli E, Uhlenhaut NH, Baldi P, Adamski J, Tschöp MH, Eckel-Mahan K, Sassone-Corsi P
JournalCell
PubMed ID30193114
Metabolic diseases are often characterized by circadian misalignment in different tissues, yet how altered coordination and communication among tissue clocks relate to specific pathogenic mechanisms remains largely unknown. Applying an integrated systems biology approach, we performed 24-hr metabolomics profiling of eight mouse tissues simultaneously. We present a temporal and spatial ... More
Inhibiting cellular uptake of mutant huntingtin using a monoclonal antibody: Implications for the treatment of Huntington's disease.
AuthorsBartl S, Oueslati A, Southwell AL, Siddu A, Parth M, David LS, Maxan A, Salhat N, Burkert M, Mairhofer A, Friedrich T, Pankevych H, Balazs K, Staffler G, Hayden MR, Cicchetti F, Smrzka OW
JournalNeurobiol Dis
PubMed ID32407769
Huntington's disease (HD) is caused by a highly polymorphic CAG trinucleotide expansion in the gene encoding for the huntingtin protein (HTT). The resulting mutant huntingtin protein (mutHTT) is ubiquitously expressed but also exhibits the ability to propagate from cell-to-cell to disseminate pathology; a property which may serve as a new ... More