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
The large size (six membrane-spanning repeats in each of four domains) and asymmetric architecture of the voltage-dependent Na+ channel has hindered determination of its structure. With the goal of determining the minimum structure of the Na+ channel permeation pathway, we created two stable cell lines expressing the voltage-dependent rat skeletal ... More
Synaptotagmin V is targeted to dense-core vesicles that undergo calcium-dependent exocytosis in PC12 cells.
'Synaptotagmins (Syts) III, V, VI, and X are classified as a subclass of Syt, based on their sequence similarities and biochemical properties (Ibata, K., Fukuda, M., and Mikoshiba, K. (1998) J. Biol. Chem. 273, 12267-12273; Fukuda, M., Kanno, E., and Mikoshiba, K. (1999) J. Biol. Chem. 274, 31421-31427). Although they ... More
Src-dependent phosphorylation of the epidermal growth factor receptor on tyrosine 845 is required for zinc-induced Ras activation.
Authors Wu Weidong; Graves Lee M; Gill Gordon N; Parsons Sarah J; Samet James M;
JournalJ Biol Chem
PubMed ID11983694
'Previous studies have shown that exposure of cells to Zn2+ ions induces Ras and MAPK activation through the EGF receptor (EGFR). To further determine the role of EGFR in Zn2+-induced signaling, mouse B82L fibroblasts expressing no detectable EGFR protein (B82L-par), wild type EGFR (B82L-wt), kinase-deficient EGFR (B82L-K721M), or COOH-truncated EGFR ... 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
Galpha 12 and galpha 13 negatively regulate the adhesive functions of cadherin.
Authors Meigs Thomas E; Fedor-Chaiken Mary; Kaplan Daniel D; Brackenbury Robert; Casey Patrick J;
JournalJ Biol Chem
PubMed ID11976333
'Cadherins function to promote adhesion between adjacent cells and play critical roles in such cellular processes as development, tissue maintenance, and tumor suppression. We previously demonstrated that heterotrimeric G proteins of the G(12) subfamily comprised of Galpha(12) and Galpha(13) interact with the cytoplasmic domain of cadherins and cause the release ... More
Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo.
'A major concern in cancer therapy is resistance of tumors such as glioblastoma to current treatment protocols. Here, we report that transfer of the gene encoding second mitochondria-derived activator of caspase (Smac) or Smac peptides sensitized various tumor cells in vitro and malignant glioma cells in vivo for apoptosis induced ... More
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
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
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
Rhodopsin kinase: expression in mammalian cells and a two-step purification.
AuthorsBruel C, Cha K, Reeves PJ, Getmanova E, Khorana HG
JournalProc Natl Acad Sci U S A
PubMed ID10737781
'A suitable system for expression of the rhodopsin kinase (RK) gene and its mutants is needed for structure-function studies of RK. Previously, investigation of the baculovirus system showed satisfactory production of RK, but posttranslational isoprenylation was deficient. We now report on a comparative study of expression of the RK gene ... 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
Polarization of myosin II heavy chain-protein kinase C in chemotaxing dictyostelium cells.
AuthorsRubin H, Ravid S,
JournalJ Biol Chem
PubMed ID12130648
Eukaryotic cells need morphological polarity to carry out chemotaxis (Parent, C. A., Blacklock, B. J., Froehlich, W. M., Murphy, D. B., and Devreotes, P. N. (1998) Cell 95, 81-91; Jin, T., Zhang, N., Long, Y., Parent, C., and Devreotes, P. N. (2000) Science 287, 1034-1036; Servant, G., Weiner, O. D., ... 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
The neuronal growth-associated protein (GAP)-43 (neuromodulin, B-50, F1), which is concentrated in the growth cones of elongating axons during neuronal development and in nerve terminals in restricted regions of the adult nervous system, has been implicated in the release of neurotransmitter. To study the role of GAP-43 in evoked secretion, ... More
Protein kinase C deficiency blocks recovery from agonist-induced desensitization.
Authors Shih M; Malbon C C;
JournalJ Biol Chem
PubMed ID8702931
Protein phosphorylation is central to agonist-induced attenuation of the function of G-protein-linked receptors. Stable expression of RNA antisense to specific protein kinase mRNAs permitted analysis of loss-of-function mutants of A431 human epidermoid carcinoma cells, lacking protein kinase A, protein kinase C, or beta-adrenergic receptor kinase. Deficiency of protein kinase C, ... 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
Interaction of two actin-binding proteins, synaptopodin and alpha-actinin-4, with the tight junction protein MAGI-1.
AuthorsPatrie KM, Drescher AJ, Welihinda A, Mundel P, Margolis B.
JournalJ Biol Chem
PubMed ID12042308
In an attempt to find podocyte-expressed proteins that may interact with the tight junction protein MAGI-1, we screened a glomerulus-enriched cDNA library with a probe consisting of both WW domains of MAGI-1. One of the isolated clones contained two WW domain-binding motifs and was identified as a portion of the ... More
Properties and developmental regulation of polysialyltransferase activity in the chicken embryo brain.
The properties and developmental regulation of vertebrate polysialyltransferase (PST), an enzyme activity responsible for extension of alpha 2,8-linked sialic acid homopolymers (PSA) associated with the fifth Ig domain of the neural cell adhesion molecule (NCAM). have been studied. The assay for PST used exogenous NCAM as a substrate, with a ... 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
Binding of low affinity N-formyl peptide receptors to G protein. Characterization of a novel inactive receptor intermediate.
Authors Prossnitz E R; Schreiber R E; Bokoch G M; Ye R D;
JournalJ Biol Chem
PubMed ID7738006
G protein-coupled seven-transmembrane-containing receptors, such as the N-formyl peptide receptor (FPR) of neutrophils, likely undergo a conformational change upon binding of ligand, which enables the receptor to transmit a signal to G proteins. We have examined the functional significance of numerous conserved charged amino acid residues proposed to be located ... 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
Three Novel Sarco/endoplasmic Reticulum Ca2+-ATPase (SERCA) 3 Isoforms. EXPRESSION, REGULATION, AND FUNCTION OF THE MEMBERS OF THE SERCA3 FAMILY.
Authors Martin Virginie; Bredoux Raymonde; Corvazier Elisabeth; Van Gorp Roosje; Kovacs Tunde; Gelebart Pascal; Enouf Jocelyne;
JournalJ Biol Chem
PubMed ID11956212
Sarco/endoplasmic reticulum Ca(2+)-ATPases (SERCAs) pump Ca(2+) into the endoplasmic reticulum. Recently, three human SERCA3 (h3a-c) proteins and a previously unknown rat SERCA3 (r3b/c) mRNA have been described. Here, we (i) document two novel human SERCA3 splice variants h3d and h3e, (ii) provide data for the expression and mechanisms regulating the ... More
Selective silencing of euchromatic L1s revealed by genome-wide screens for L1 regulators.
AuthorsLiu N, Lee CH, Swigut T, Grow E, Gu B, Bassik MC, Wysocka J
JournalNature
PubMed ID29211708
'Transposable elements, also known as transposons, are now recognized not only as parasitic DNA, the spread of which in the genome must be controlled by the host, but also as major players in genome evolution and regulation. Long interspersed element-1 (LINE-1, also known as L1), the only currently autonomous mobile ... More
Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3.
AuthorsFarrelly LA, Thompson RE, Zhao S, Lepack AE, Lyu Y, Bhanu NV, Zhang B, Loh YE, Ramakrishnan A, Vadodaria KC, Heard KJ, Erikson G, Nakadai T, Bastle RM, Lukasak BJ, Zebroski H, Alenina N, Bader M, Berton O, Roeder RG, Molina H, Gage FH, Shen L, Garcia BA, Li H, Muir TW, Maze I
JournalNature
PubMed ID30867594
Chemical modifications of histones can mediate diverse DNA-templated processes, including gene transcription
ROCK inhibitors upregulate the neuroprotective Parkin-mediated mitophagy pathway.
AuthorsMoskal N, Riccio V, Bashkurov M, Taddese R, Datti A, Lewis PN, Angus McQuibban G
JournalNat Commun
PubMed ID31900402
The accumulation of damaged mitochondria causes the death of dopaminergic neurons. The Parkin-mediated mitophagy pathway functions to remove these mitochondria from cells. Targeting this pathway represents a therapeutic strategy for several neurodegenerative diseases, most notably Parkinson's disease. We describe a discovery pipeline to identify small molecules that increase Parkin recruitment ... More