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 inhibited by long chain fatty acids such as oleic acid (C18, delta 9) at physiological plasma concentrations. Inhibition of single chain urokinase binding to human trophoblastic cells by long chain fatty acids was dose-dependent and saturable. Fifty percent of the binding was inhibited at an oleic acid concentration of 27 microM, while inhibition was maximal (75%) at 150 microM oleic acid. The inhibitory potency of oleic acid was unaffected by fatty acid free albumin or human plasma. Inhibition of single chain urokinase binding by free fatty acid analogues was critically dependent on chain length (> C14 required for inhibition) and was proportional to the extent of unsaturation. Only the fraction of specific scuPA binding to trophoblasts that was dependent on uPAR was susceptible to inhibition by oleic acid, while binding of scuPA to vitronectin, thombospondin, and the alpha 2-macroglobulin receptor/low-density lipoprotein-related receptor was not. [3H]Oleic acid bound specifically to recombinant soluble uPAR in a 1:1 molar ratio in the presence or absence of plasma and totally blocked its specific binding to a cell line expressing glycosyl phosphatidylinositol-linked single chain urokinase. These results indicate that oleic acid and other unsaturated long chain free fatty acids may serve as physiologic regulators of proteolytic events and intracellular signalling that depend upon the interaction of urokinase with its receptor.

journal_name

Biochemistry

journal_title

Biochemistry

authors

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

doi

10.1021/bi9514774

subject

Has Abstract

pub_date

1996-05-28 00:00:00

pages

6884-90

issue

21

eissn

0006-2960

issn

1520-4995

pii

bi9514774

journal_volume

35

pub_type

杂志文章
  • Comparative studies on the 7-iodo and 7-fluoro derivatives of N-acetoxy-N-2-acetylaminofluorene: binding sites on DNA and conformational change of modified deoxytrinucleotides.

    abstract::GMP and native DNA were reacted with 7-iodo and 7-fluoro derivatives of N-acetoxy-N-2-acetylaminofluorene. It was shown that the 7-halogeno derivatives react on C-8 of guanine. Furthermore the respective amount of arylamidation (covalent linkage on the C-8 of guanine) and arylation (covalent linkage on 2-NH2 groups of...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00606a016

    authors: Lefèvre JF,Fuchs RP,Daune MP

    更新日期:1978-06-27 00:00:00

  • Peptidylglycine alpha-hydroxylating monooxygenase: active site residues, disulfide linkages, and a two-domain model of the catalytic core.

    abstract::Peptidylglycine alpha-hydroxylating monooxygenase (PHM) is a copper, ascorbate, and molecular oxygen dependent enzyme that catalyzes the first step leading to the C-terminal amidation of glycine-extended peptides. The catalytic core of PHM (PHMcc), refined to residues 42-356 of the PHM protein, was expressed at high l...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi9708747

    authors: Kolhekar AS,Keutmann HT,Mains RE,Quon AS,Eipper BA

    更新日期:1997-09-09 00:00:00

  • Dynamic structure of a highly ordered beta-sheet molten globule: multiple conformations with a stable core.

    abstract::The structure of [14-38]Abu, a variant of bovine pancreatic trypsin inhibitor (BPTI) with only the 14-38 disulfide bridge intact, has been analyzed by two-dimensional 1H and 1H-15N NMR. Except for the 18-24, 29-35 antiparallel beta-sheet, residues in all regions of the molecule give two exchange cross peaks for each 1...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00036a015

    authors: Barbar E,Barany G,Woodward C

    更新日期:1995-09-12 00:00:00

  • A mutational analysis of binding interactions in an antigen-antibody protein-protein complex.

    abstract::Alanine scanning mutagenesis, double mutant cycles, and X-ray crystallography were used to characterize the interface between the anti-hen egg white lysozyme (HEL) antibody D1.3 and HEL. Twelve out of the 13 nonglycine contact residues on HEL, as determined by the high-resolution crystal structure of the D1.3-HEL comp...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi980148j

    authors: Dall'Acqua W,Goldman ER,Lin W,Teng C,Tsuchiya D,Li H,Ysern X,Braden BC,Li Y,Smith-Gill SJ,Mariuzza RA

    更新日期:1998-06-02 00:00:00

  • Mechanistic studies with solubilized rat liver steroid 5 alpha-reductase: elucidation of the kinetic mechanism.

    abstract::A solubilized preparation of steroid 5 alpha-reductase (EC 1.3.1.30) from rat liver has been used in studies focused toward an understanding of the kinetic mechanism associated with enzyme catalysis. From the results of analyses with product and dead-end inhibitors, a preferentially ordered binding of substrates and r...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00463a025

    authors: Levy MA,Brandt M,Greway AT

    更新日期:1990-03-20 00:00:00

  • Site-directed mutagenesis of putative active site residues of 5-enolpyruvylshikimate-3-phosphate synthase.

    abstract::The site-directed mutagenesis of a number of proposed active site residues of 5-enolpyruvyl shikimate-3-phosphate (EPSP) synthase is reported. Several of these mutations resulted in complete loss of enzyme activity indicating that these residues are probably involved with catalysis, notably K22R, K411R, D384A, R27A, R...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi9815142

    authors: Shuttleworth WA,Pohl ME,Helms GL,Jakeman DL,Evans JN

    更新日期:1999-01-05 00:00:00

  • Cysteine auxotrophy of human leukemic lymphoblasts is associated with decreased amounts of intracellular cystathionase protein.

    abstract::A series of human lymphoblastoid cell lines derived from nonleukemic donors are known to be cysteine prototrophs (cys+), while several lymphoblastoid lines derived from leukemic donors are cysteine auxotrophs (cys-). We have tested representative cell lines of each type for their content of cystathionase enzyme activi...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00508a041

    authors: Glode LM,Kriegler MP,Livingston DM

    更新日期:1981-03-03 00:00:00

  • Ca2+ dependence of the distance between Cys-98 of troponin C and Cys-133 of troponin I in the ternary troponin complex. Resonance energy transfer measurements.

    abstract::We have used resonance energy transfer to study the spatial relationship between Cys-98 of rabbit skeletal troponin C and Cys-133 of rabbit skeletal troponin I in the reconstituted ternary troponin complex. The donor was introduced by labeling either troponin C or troponin I with N-(iodoacetyl)-N'-(5-sulfo-1-naphthyl)...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00440a029

    authors: Tao T,Gowell E,Strasburg GM,Gergely J,Leavis PC

    更新日期:1989-07-11 00:00:00

  • Purification and immunogenicity of fusion VP1 protein of foot and mouth disease virus.

    abstract::A procedure has been developed to purify foot and mouth disease virus (FMDV) VP1 surface antigens from recombinant Escherichia coli. The VP1 antigens are expressed as fusion proteins derived from the E. coli Trp operon and VP1 surface protein of FMDV. The procedure is capable of recovering greater than 96% of the desi...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00321a031

    authors: Shire SJ,Bock L,Ogez J,Builder S,Kleid D,Moore DM

    更新日期:1984-12-18 00:00:00

  • Calcium-Induced Lipid Nanocluster Structures: Sculpturing of the Plasma Membrane.

    abstract::The plasma membrane of the cell is a complex, tightly regulated, heterogeneous environment shaped by proteins, lipids, and small molecules. Ca2+ ions are important cellular messengers, spatially separated from anionic lipids. After cell injury, disease, or apoptotic events, anionic lipids are externalized to the outer...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/acs.biochem.8b01069

    authors: Hallock MJ,Greenwood AI,Wang Y,Morrissey JH,Tajkhorshid E,Rienstra CM,Pogorelov TV

    更新日期:2018-12-18 00:00:00

  • Structure-function relationships of the Escherichia coli ATP synthase probed by trypsin digestion.

    abstract::Trypsin cleavage has been used to probe structure-function relationships of the Escherichia coli ATP synthase (ECF1F0). Trypsin cleaved all five subunits, alpha, beta, gamma, delta, and epsilon, in isolated ECF1. Cleavage of the alpha subunit involved the removal of the N-terminal 15 residues, the beta subunit was cle...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00402a016

    authors: Gavilanes-Ruiz M,Tommasino M,Capaldi RA

    更新日期:1988-01-26 00:00:00

  • Osmoelastic coupling in biological structures: formation of parallel bundles of actin filaments in a crystalline-like structure caused by osmotic stress.

    abstract::A high molecular weight inert molecule, poly(ethylene glycol) (PEG), or a soluble protein, ovalbumin, causes parallel bundles of actin filaments in a crystalline-like structure under physiological conditions of ionic compositions and pH. The bundle formation depends on the molecular weight of PEG, and a larger molecul...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00441a052

    authors: Suzuki A,Yamazaki M,Ito T

    更新日期:1989-07-25 00:00:00

  • Structure of human transferrin receptor oligosaccharides: conservation of site-specific processing.

    abstract::The human transferrin receptor (TfR) has three N-linked oligosaccharides. A combination of site-directed mutagenesis and carbohydrate and protein chemistry was used to characterize the structures of the N-linked oligosaccharides and to map their locations. We find that the type of oligosaccharide at each position was ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi962884y

    authors: Hayes GR,Williams AM,Lucas JJ,Enns CA

    更新日期:1997-04-29 00:00:00

  • Functional annotation and three-dimensional structure of an incorrectly annotated dihydroorotase from cog3964 in the amidohydrolase superfamily.

    abstract::The substrate specificities of two incorrectly annotated enzymes belonging to cog3964 from the amidohydrolase superfamily were determined. This group of enzymes are currently misannotated as either dihydroorotases or adenine deaminases. Atu3266 from Agrobacterium tumefaciens C58 and Oant2987 from Ochrobactrum anthropi...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi301483z

    authors: Ornelas A,Korczynska M,Ragumani S,Kumaran D,Narindoshvili T,Shoichet BK,Swaminathan S,Raushel FM

    更新日期:2013-01-08 00:00:00

  • Human Cytosolic and Mitochondrial Serine Hydroxymethyltransferase Isoforms in Comparison: Full Kinetic Characterization and Substrate Inhibition Properties.

    abstract::Serine hydroxymethyltransferase (SHMT) catalyzes the reversible conversion of l-serine and tetrahydrofolate into glycine and 5,10-methylenetetrahydrofolate. This enzyme, which plays a pivotal role in one-carbon metabolism, is involved in cancer metabolic reprogramming and is a recognized target of chemotherapy interve...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/acs.biochem.8b01074

    authors: Tramonti A,Nardella C,di Salvo ML,Barile A,Cutruzzolà F,Contestabile R

    更新日期:2018-12-26 00:00:00

  • Molecular design of new inhibitors of peroxidase activity of cytochrome c/cardiolipin complexes: fluorescent oxadiazole-derivatized cardiolipin.

    abstract::Interaction of a mitochondria-specific anionic phospholipid, cardiolipin (CL), with an intermembrane protein, cytochrome c (cyt c), yields a peroxidase complex. During apoptosis, the complex induces accumulation of CL oxidation products that are essential for detachment of cyt c from the mitochondrial membrane, induct...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi801507s

    authors: Borisenko GG,Kapralov AA,Tyurin VA,Maeda A,Stoyanovsky DA,Kagan VE

    更新日期:2008-12-23 00:00:00

  • Phosphoprotein particles: calcium and inorganic phosphate binding structures.

    abstract::Phosphoprotein particles were isolated in their native state from the physiological fluid of the estuarine clam Rangia cuneata , and the characteristics of the mineral ion-protein complex which constitutes the native particle were investigated by using mineral ion binding and mineral ion exchange techniques. The parti...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00302a017

    authors: Marsh ME,Sass RL

    更新日期:1984-03-27 00:00:00

  • Cryoenzymic studies on actomyosin ATPase. Evidence that the degree of saturation of actin with myosin subfragment 1 affects the kinetics of the binding of ATP.

    abstract::The initial steps of actomyosin subfragment 1 (acto-S1) ATPase (dissociation and binding of ATP) were studied at -15 degrees C with 40% ethylene glycol as antifreeze. The dissociation kinetics were followed by light scattering in a stopped-flow apparatus, and the binding of ATP was followed by the ATP chase method in ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00459a026

    authors: Tesi C,Travers F,Barman T

    更新日期:1990-02-20 00:00:00

  • Relaxing the nicotinamide cofactor specificity of phosphite dehydrogenase by rational design.

    abstract::Homology modeling was used to identify two particular residues, Glu175 and Ala176, in Pseudomonas stutzeri phosphite dehydrogenase (PTDH) as the principal determinants of nicotinamide cofactor (NAD(+) and NADP(+)) specificity. Replacement of these two residues by site-directed mutagenesis with Ala175 and Arg176 both s...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi035018b

    authors: Woodyer R,van der Donk WA,Zhao H

    更新日期:2003-10-14 00:00:00

  • Kinetic isotope effects on the oxidation of reduced nicotinamide adenine dinucleotide phosphate by the flavoprotein methylenetetrahydrofolate reductase.

    abstract::Previous work from this laboratory has established that the NADPH-menadione oxidoreductase reaction catalyzed by methylenetetrahydrofolate reductase from pig liver proceeds by Ping Pong Bi Bi kinetics and that the reductive half-reaction is rate limiting in steady-state turnover. We have now shown that methylenetetrah...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00317a027

    authors: Vanoni MA,Matthews RG

    更新日期:1984-10-23 00:00:00

  • Interaction of fibrin(ogen) with heparin: further characterization and localization of the heparin-binding site.

    abstract::The beta chain 15-42 sequence of the fibrin(ogen) E region was implicated in heparin binding [Odrljin et al. (1996) Blood 88, 2050-2061]; whether heparin binds to other fibrin(ogen) regions remains to be clarified. To address this question, we studied the interaction of heparin with fibrinogen, fibrin, and their major...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi0344073

    authors: Yakovlev S,Gorlatov S,Ingham K,Medved L

    更新日期:2003-07-01 00:00:00

  • Effect of monoclonal antibody binding on alpha-beta gamma subunit interactions in the rod outer segment G protein, Gt.

    abstract::The guanyl nucleotide binding regulatory protein of retinal rod outer segments, called Gt, that couples the photon receptor rhodopsin with the light-activated cGMP phosphodiesterase, can be resolved into two functional components, alpha t and beta gamma t. The effect of monoclonal antibody binding to the alpha t subun...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00451a047

    authors: Mazzoni MR,Hamm HE

    更新日期:1989-12-12 00:00:00

  • Delta-elimination by T4 endonuclease V at a thymine dimer site requires a secondary binding event and amino acid Glu-23.

    abstract::Endonuclease V from bacteriophage T4 is a well characterized enzyme that initiates the repair of ultraviolet light induced pyrimidine dimers. Scission of the phosphodiester backbone between the pyrimidines within a dimer, or 3' to an abasic (AP) site, occurs by a beta-elimination mechanism. In addition, high concentra...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00027a031

    authors: Latham KA,Lloyd RS

    更新日期:1995-07-11 00:00:00

  • Solvent interaction of a Hsp70 chaperone substrate-binding domain investigated with water-NOE NMR experiments.

    abstract::The interaction of solvent of the substrate binding domain of the bacterial heat shock 70 chaperone protein DnaK was studied in its apo form and with bound hydrophobic substrate peptide, using refined nuclear magnetic resonance experiments. Distinct differences between the two states of the protein were observed. Acco...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi030097c

    authors: Cai S,Stevens SY,Budor AP,Zuiderweg ER

    更新日期:2003-09-30 00:00:00

  • Glucocerebroside transfer between phosphatidylcholine bilayers.

    abstract::We have studied the kinetics of transfer of glucocerebroside between phospholipid bilayers by using pyrene and 3H-labeled glucocerebroside incorporated into dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) bilayers. Pyrene-labeled glucocerebroside (PyrCer) molecules are able to form an e...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00535a021

    authors: Correa-Freire MC,Barenholz Y,Thompson TE

    更新日期:1982-03-16 00:00:00

  • Solvent effects on the kinetics and thermodynamics of stacking in poly(cytidylic acid).

    abstract::The Raman laser temperature-jump technique has been used to measure the kinetics of the coil to helix reaction of poly(cytidylic acid) [poly(C)] in aqueous cosolvent mixtures. The rate of helix formation has a low activation energy and is proportional to reciprocal solvent viscosity. The observations suggest helix for...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00509a003

    authors: Freier SM,Hill KO,Dewey TG,Marky LA,Breslauer KJ,Turner DH

    更新日期:1981-03-17 00:00:00

  • The stability, structural organization, and denaturation of pectate lyase C, a parallel beta-helix protein.

    abstract::Pectate lyase C (pelC) was the first protein in which the parallel beta-helix structure was recognized. The unique features of parallel beta-helix-containing proteins-a relatively simple topology and unusual interactions among side chains-make pelC an interesting protein to study with respect to protein folding. In th...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi001900v

    authors: Kamen DE,Griko Y,Woody RW

    更新日期:2000-12-26 00:00:00

  • Multiple conformational changes in enzyme catalysis.

    abstract::Understanding the molecular mechanisms of enzyme catalysis and allosteric regulation has been a primary goal of biochemistry for many years. The dynamics of these processes, approached through a variety of kinetic methods, are discussed. The results obtained for many different enzymes suggest that multiple intermediat...

    journal_title:Biochemistry

    pub_type: 杂志文章,评审

    doi:10.1021/bi0260839

    authors: Hammes GG

    更新日期:2002-07-02 00:00:00

  • Bimodal action of alkaline earth cations on Dictyostelium discoideum ribonuclease P activity.

    abstract::The ribonucleoprotein ribonuclease P (RNase P) cleaves all tRNA precursors endonucleolitically to produce the mature 5'-end. Dictyostelium discoideum RNase P displays an absolute requirement for Mg2+. Only the alkaline earth cations Ca2+, Sr2+, and Ba2+, under appropriate conditions can substitute to some extent for M...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi9808971

    authors: Tekos A,Stathopoulos C,Drainas D

    更新日期:1998-11-03 00:00:00

  • Characterization of Natural Colibactin-Nucleobase Adducts by Tandem Mass Spectrometry and Isotopic Labeling. Support for DNA Alkylation by Cyclopropane Ring Opening.

    abstract::Colibactins are genotoxic secondary metabolites whose biosynthesis is encoded in the clb gene cluster harbored by certain strains of gut commensal Escherichia coli. Using synthetic colibactin analogues, we previously provided evidence that colibactins alkylate DNA by addition of a nucleotide to an electrophilic cyclop...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/acs.biochem.8b01023

    authors: Xue M,Shine E,Wang W,Crawford JM,Herzon SB

    更新日期:2018-11-13 00:00:00