Activation of overexpressed receptors for insulin and epidermal growth factor interferes in mitogenic signaling without affecting the activation of p21ras.


:Activated receptors with a tyrosine kinase activity induce a variety of responses like changes in the differentiation and mitogenic status of cells. These responses are mediated in part by p21ras. Some of these activated receptors induce in certain cell types a pronounced, but transient, increase in Ras-GTP. We have stimulated cells with insulin, epidermal growth factor (EGF), and fetal calf serum (FCS), and the mitogenic response, as reflected by stimulation of [3H]thymidine incorporation, was compared with the magnitude of the transient increase in Ras-GTP levels. Cell lines were used that expressed both physiological and elevated numbers of p21ras and receptors for insulin and EGF, respectively. In all the examined cell lines 9% FCS did not induce a marked increase in Ras-GTP despite its high mitogenic potency. Pronounced increases in Ras-GTP levels were observed in insulin-stimulated CHO cells which overexpress insulin receptors whereas in the parental CHO cells only a small increase is seen. Insulin (1 microM) and FCS (9%) stimulate [3H]thymidine incorporation in parental CHO cells to a similar high level whereas in insulin receptor overexpressing CHO cells the maximum of insulin-stimulated [3H]thymidine incorporation is only 55% of the level reached by 9% FCS. In those cells the maximum is already reached at low (1 nM) insulin concentrations. Remarkably, at higher insulin concentrations stimulation of [3H]thymidine incorporation starts to decrease strongly despite the fact that the magnitude of the transient increase in Ras-GTP and subsequent MAPkinase activation increases. Similarly, when EGF receptors are overexpressed in Rat-1 cells, the mitogenic response is also decreased at higher EGF concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)






Osterop AP,Medema RH,Ouwens DM,Van der Zon GC,Möller W,Maassen JA




Has Abstract


1994-06-14 00:00:00












  • The activities of recombinant gamma-carboxyglutamic-acid-deficient mutants of activated human protein C toward human coagulation factor Va and factor VIII in purified systems and in plasma.

    abstract::The dependence of the activity of recombinant activated human protein C (r-APC) on each of its nine gamma-carboxyglutamic (Gla) residues (sequence positions 6, 7, 14, 16, 19, 20, 25, 26, and 29) has been assessed in purified systems and in plasma using r-mutants in which each Gla residue of r-APC was individually alte...


    pub_type: 杂志文章


    authors: Jhingan A,Zhang L,Christiansen WT,Castellino FJ

    更新日期:1994-02-22 00:00:00

  • Identification of contact sites between ankyrin and band 3 in the human erythrocyte membrane.

    abstract::The red cell membrane is stabilized by a spectrin/actin-based cortical cytoskeleton connected to the phospholipid bilayer via multiple protein bridges. By virtue of its interaction with ankyrin and adducin, the anion transporter, band 3 (AE1), contributes prominently to these bridges. In a previous study, we demonstra...


    pub_type: 杂志文章


    authors: Grey JL,Kodippili GC,Simon K,Low PS

    更新日期:2012-08-28 00:00:00

  • Thermomechanical and transition properties of dimyristoylphosphatidylcholine/cholesterol bilayers.

    abstract::Mixtures of dimyristoylphosphatidylcholine (DMPC) and cholesterol (Chol) have been used to examine the effects of cholesterol on the chain crystallization transitions and thermomechanical properties in phospholipid bilayer membranes. The mechanical properties--elastic moduli and level of tension at membrane rupture--w...


    pub_type: 杂志文章


    authors: Needham D,McIntosh TJ,Evans E

    更新日期:1988-06-28 00:00:00

  • Calcium-modulated guanylate cyclase transduction machinery in the photoreceptor--bipolar synaptic region.

    abstract::Rod outer segment membrane guanylate cyclase (ROS-GC) transduction system is a central component of the Ca(2+)-sensitive phototransduction machinery. The system is composed of two parts: Ca(2+) sensor guanylate cyclase activating protein (GCAP) and ROS-GC. GCAP senses Ca(2+) impulses and inhibits the cyclase. This ope...


    pub_type: 杂志文章


    authors: Venkataraman V,Duda T,Vardi N,Koch KW,Sharma RK

    更新日期:2003-05-20 00:00:00

  • Translation of collagen messenger RNA in a cell-free system derived from wheat germ.

    abstract::A cell-free system for synthesizing protein from wheat germ was used to translate the messenger RNA extracted from 16-day embryonic chick calvaria. A part of the product had properties similar to collagenous peptides and served as a substrate for prolyl hydroxylase, an enzyme specific for collagen. The level of potass...


    pub_type: 杂志文章


    authors: Benveniste K,Wilczek J,Ruggieri A,Stern R

    更新日期:1976-02-24 00:00:00

  • Peptidomics of prolyl endopeptidase in the central nervous system.

    abstract::Prolyl endopeptidase (Prep) is a member of the prolyl peptidase family and is of interest because of its unique biochemistry and connections to cognitive function. Using an unbiased mass spectrometry (MS)-based peptidomics platform, we identified Prep-regulated peptides in the central nervous system (CNS) of mice by m...


    pub_type: 杂志文章


    authors: Nolte WM,Tagore DM,Lane WS,Saghatelian A

    更新日期:2009-12-22 00:00:00

  • pH-Dependent Binding of Chloride to a Marine Alkaline Phosphatase Affects the Catalysis, Active Site Stability, and Dimer Equilibrium.

    abstract::The effect of ionic strength on enzyme activity and stability varies considerably between enzymes. Ionic strength is known to affect the catalytic activity of some alkaline phosphatases (APs), such as Escherichia coli AP, but how ions affect APs is debated. Here, we studied the effect of various ions on a cold-adapted...


    pub_type: 杂志文章


    authors: Hjörleifsson JG,Ásgeirsson B

    更新日期:2017-09-26 00:00:00

  • Ultraviolet damage and nucleosome folding of the 5S ribosomal RNA gene.

    abstract::The Xenopus borealis somatic 5S ribosomal RNA gene was used as a model system to determine the mutual effects of nucleosome folding and formation of ultraviolet (UV) photoproducts (primarily cis-syn cyclobutane pyrimidine dimers, or CPDs) in chromatin. We analyzed the preferred rotational and translational settings of...


    pub_type: 杂志文章


    authors: Liu X,Mann DB,Suquet C,Springer DL,Smerdon MJ

    更新日期:2000-01-25 00:00:00

  • 111Cd NMR studies of the domain specificity of Ag+ and Cu+ binding to metallothionein.

    abstract::Metal displacement reactions of Cd7MT with Ag+ or Cu+ and interprotein metal exchange reactions between Cd7MT and Ag12MT or Cu12MT were studied by 111Cd NMR. Titration of 111Cd7MT with Ag+ indicates that Ag+ binds preferentially to the beta-domain of the protein to form the metal hybrid species, (Cd4)alpha(Ag6)beta MT...


    pub_type: 杂志文章


    authors: Li H,Otvos JD

    更新日期:1996-11-05 00:00:00

  • TFEC can function as a transcriptional activator of the nonmuscle myosin II heavy chain-A gene in transfected cells.

    abstract::Transcription of the human nonmuscle myosin II heavy chain-A (NMHC-A) gene is regulated via multiple elements located in intron 1, including element F which contains an E-box. In this study we have identified and characterized the factors that are capable of binding to element F. Yeast one-hybrid screening using eleme...


    pub_type: 杂志文章


    authors: Chung MC,Kim HK,Kawamoto S

    更新日期:2001-07-31 00:00:00

  • X-ray Structures of the Proprotein Convertase Furin Bound with Substrate Analogue Inhibitors Reveal Substrate Specificity Determinants beyond the S4 Pocket.

    abstract::The proprotein convertase furin is a highly specific serine protease modifying and thereby activating proteins in the secretory pathway by proteolytic cleavage. Its substrates are involved in many diseases, including cancer and infections caused by bacteria and viruses. Understanding furin's substrate specificity is c...


    pub_type: 杂志文章


    authors: Dahms SO,Hardes K,Steinmetzer T,Than ME

    更新日期:2018-02-13 00:00:00

  • Alternatively spliced form of human thyroperoxidase, TPOzanelli: activity, intracellular trafficking, and role in hormonogenesis.

    abstract::Thyroperoxidase (TPO), a type I transmembrane heme containing glycoprotein, catalyzes iodide organification and thyroid hormone synthesis. One of the two main alternatively spliced forms of this enzyme, TPOzanelli, which is present in Graves's disease thyroid tissue, has a cytoplasmic domain completely modified. In th...


    pub_type: 杂志文章


    authors: Niccoli-Sire P,Fayadat L,Siffroi-Fernandez S,Malthierry Y,Franc JL

    更新日期:2001-02-27 00:00:00

  • Engineering the substrate binding site of benzoylformate decarboxylase.

    abstract::Benzoylformate decarboxylase (BFDC) and pyruvate decarboxylase (PDC) are both thiamin diphosphate-dependent enzymes. The two share a common three-dimensional structure and catalyze a similar chemical reaction, i.e., decarboxylation of 2-keto acids. However, they vary significantly in their substrate utilization patter...


    pub_type: 杂志文章


    authors: Yep A,McLeish MJ

    更新日期:2009-09-08 00:00:00

  • Unesterified long chain fatty acids inhibit the binding of single chain urokinase to the urokinase receptor.

    abstract::The interaction of single chain urokinase with its receptor accelerates plasminogen activator activity on cell surfaces and induces intracellular signalling in several cell types. To date, no physiologic inhibitor of this binding has been identified. We report that the binding of scuPA to its cellular receptor is inhi...


    pub_type: 杂志文章


    authors: al-Roof Higazi A,Aceto JF,Kniss D,Upson R,Cohen R,Dichek DA,Cines DB

    更新日期:1996-05-28 00:00:00

  • Effects of lipids and long-chain alkyl derivatives on the activity of (Ca2+-Mg2+)-ATPase.

    abstract::The ATPase activity of the (Ca2+-Mg2+)-ATPase reconstituted into bilayers of phosphatidylcholines depends on the fatty acyl chain length of the phospholipids. It is shown that the fluorescence response to Ca2+ of the ATPase modified with fluorescein isothiocyanate is also dependent on phospholipid structure and is int...


    pub_type: 杂志文章


    authors: Froud RJ,East JM,Jones OT,Lee AG

    更新日期:1986-11-18 00:00:00

  • Synchronization of the three reaction centers within carbamoyl phosphate synthetase.

    abstract::Carbamoyl phosphate synthetase from E. coli catalyzes the synthesis of carbamoyl phosphate through a series of four reactions occurring at three active sites connected by a molecular tunnel of 100 A. To understand the mechanism for coordination and synchronization among the active sites, the pre-steady-state time cour...


    pub_type: 杂志文章


    authors: Miles BW,Raushel FM

    更新日期:2000-05-02 00:00:00

  • Portability of epimerization domain and role of peptidyl carrier protein on epimerization activity in nonribosomal peptide synthetases.

    abstract::Incorporation of nonproteinogenic amino acids in small polypeptides synthesized by nonribosomal peptide synthetases (NRPS) significantly contributes to their biological activity. In these peptides, conversion of L-amino acids to the corresponding D-isomer is catalyzed by specialized NRPS modules that utilize an epimer...


    pub_type: 杂志文章


    authors: Linne U,Doekel S,Marahiel MA

    更新日期:2001-12-25 00:00:00

  • Effects of DNA structure on oxopropenylation by the endogenous mutagens malondialdehyde and base propenal.

    abstract::Malondialdehyde (MDA) and nucleobase propenals can transfer oxopropenyl groups to guanine residues of DNA to yield pyrimodopurinone (M(1)G) adducts. The DNA structural requirements for reaction with alpha,beta-unsaturated aldehydes were explored. We found that single-stranded DNA is more sensitive to oxopropenylation ...


    pub_type: 杂志文章


    authors: Plastaras JP,Dedon PC,Marnett LJ

    更新日期:2002-04-16 00:00:00

  • Exposure of endogenous phosphatidylserine at the outer surface of stimulated platelets is reversed by restoration of aminophospholipid translocase activity.

    abstract::Phosphatidylserine (PS) in the plasma membrane of nonactivated human platelets is almost entirely located on the cytoplasmic side. Stimulation of platelets with the Ca2+ ionophore A23187 or combined action of collagen plus thrombin results in a rapid loss of the asymmetric distribution of PS. Also, treatment with the ...


    pub_type: 杂志文章


    authors: Bevers EM,Tilly RH,Senden JM,Comfurius P,Zwaal RF

    更新日期:1989-03-21 00:00:00

  • Structure of the interhelical loops and carboxyl terminus of bacteriorhodopsin by X-ray diffraction using site-directed heavy-atom labeling.

    abstract::The positions of single amino acids in the interhelical loop regions and the C-terminal tail of bacteriorhodopsin (bR) were investigated by X-ray diffraction using site-directed heavy-atom labeling. Since wild-type bR does not contain any cysteines, appropriate cysteine mutants were produced with a unique sulfhydryl g...


    pub_type: 杂志文章


    authors: Behrens W,Alexiev U,Mollaaghababa R,Khorana HG,Heyn MP

    更新日期:1998-07-21 00:00:00

  • Purification, characterization, and investigation of the mechanism of aminoglycoside 3'-phosphotransferase type Ia.

    abstract::Aminoglycoside 3'-phosphotransferases [APH(3')s] are the most common cause of bacterial high-level resistance to aminoglycoside antibiotics in clinical isolates. A one-step affinity chromatography was used to purify APH(3') type Ia. The kinetic parameters for turnover of seven aminoglycosides and the corresponding min...


    pub_type: 杂志文章


    authors: Siregar JJ,Miroshnikov K,Mobashery S

    更新日期:1995-10-03 00:00:00

  • von Willebrand factor antagonizes nitric oxide synthase to promote insulin resistance during hypoxia.

    abstract::Hypoxic respiratory diseases or hypoxia exposures are frequently accompanied by glucose intolerance and impaired nitric oxide (NO) availability. However, the molecular mechanism responsible for impaired NO production and insulin resistance (IR) during hypoxia remains obscure. In this study, we investigated the possibl...


    pub_type: 杂志文章


    authors: Singh B,Biswas I,Garg I,Sugadev R,Singh AK,Dey S,Khan GA

    更新日期:2014-01-14 00:00:00

  • Formation of hybrid luciferases from subunits of different species of Photobacterium.

    abstract::Enzyme divergence within three species of the genus Photobacterium (P. fischeri, P. leiognathi, and P. phosphoreum) was studied by comparing the catalytic characteristics and quaternary interactions of bacterial luciferases isolated from each species. Each luciferase was composed of two subunits of different molecular...


    pub_type: 杂志文章


    authors: Ruby EG,Hastings JW

    更新日期:1980-10-28 00:00:00

  • Determination of the secondary structure and molecular topology of interleukin-1 beta by use of two- and three-dimensional heteronuclear 15N-1H NMR spectroscopy.

    abstract::A study of the regular secondary structure elements of recombinant human interleukin-1 beta has been carried out using NMR spectroscopy. Using a randomly 15N labeled sample, a number of heteronuclear three- and two-dimensional NMR experiments have been performed, which have enabled a complete analysis of short-, mediu...


    pub_type: 杂志文章


    authors: Driscoll PC,Gronenborn AM,Wingfield PT,Clore GM

    更新日期:1990-05-15 00:00:00

  • The histone binding protein nucleoplasmin does not facilitate binding of transcription factor IIIA to nucleosomal Xenopus laevis 5S rRNA genes.

    abstract::In an attempt to understand the mechanism by which transcription factors compete with histone octamers for cognate binding sites in chromatin, the effect of the histone binding protein nucleoplasmin on the binding of TFIIIA to nucleosomal 5S rRNA genes was tested. In this study, it was shown that, despite the previous...


    pub_type: 杂志文章


    authors: Howe L,Itoh T,Katagiri C,Ausio J

    更新日期:1998-02-03 00:00:00

  • Distal pocket polarity in ligand binding to myoglobin: deoxy and carbonmonoxy forms of a threonine68(E11) mutant investigated by X-ray crystallography and infrared spectroscopy.

    abstract::The crystal structures of the deoxy and carbonmonoxy forms of a distal pocket myoglobin mutant in which valine68(E11) is replaced by threonine have been solved to 2.1- and 2.2-A resolution, respectively. This substitution has been shown previously to cause large decreases in the rate of oxygen binding and to lower the...


    pub_type: 杂志文章


    authors: Cameron AD,Smerdon SJ,Wilkinson AJ,Habash J,Helliwell JR,Li T,Olson JS

    更新日期:1993-12-07 00:00:00

  • Electrophoretic mobilities and diffusion coefficients of hemoglobin at high pH.

    abstract::Diffusion studies by photon correlation of scattered laser light confirm the dissociation of the tetrameric form of human carboxyhemoglobin to dimers above pH 10 and provide new estimates of the subunit dissociation equilibrium constants in this pH range. Electrophoretic light-scattering experiments under the same con...


    pub_type: 杂志文章


    authors: Haas DD,Ware BR

    更新日期:1978-11-14 00:00:00

  • FTIR spectroscopic characterization of the cytochrome aa3 from Acidianus ambivalens: evidence for the involvement of acidic residues in redox coupled proton translocation.

    abstract::The aa(3)-type quinol oxidase from Acidianus ambivalens is a divergent member of the heme-copper oxidases superfamily, namely, concerning the putative channels for intraprotein proton conduction. In this study, we used electrochemically induced FTIR difference spectroscopy to identify residues involved in redox-couple...


    pub_type: 杂志文章


    authors: Hellwig P,Gomes CM,Teixeira M

    更新日期:2003-05-27 00:00:00

  • Engineering of fibroblast growth factor: alteration of receptor binding specificity.

    abstract::A five-residue loop structure in basic fibroblast growth factor (FGF-2) which extends from amino acid residue 118 to residue 122 was replaced, by cassette mutagenesis, with the corresponding seven-residue loop structure from the structural homologue acidic fibroblast growth factor (FGF-1) or the corresponding five-res...


    pub_type: 杂志文章


    authors: Seddon AP,Aviezer D,Li LY,Böhlen P,Yayon A

    更新日期:1995-01-24 00:00:00

  • Evidence for targeted gene delivery to Hep G2 hepatoma cells in vitro.

    abstract::We have developed a system for targeting foreign DNA to hepatocytes in vitro using a soluble DNA carrier that takes advantage of receptor-mediated endocytosis to achieve internalization. The idea is based on the fact that hepatocytes possess a unique receptor that binds and internalizes galactose-terminal (asialo)glyc...


    pub_type: 杂志文章


    authors: Wu GY,Wu CH

    更新日期:1988-02-09 00:00:00