Evidence that a guanine nucleotide-binding protein linked to a muscarinic receptor inhibits directly phospholipase C.

Abstract:

:The mechanism of phospholipase C regulation by inhibitory receptors was analyzed both in intact and in permeabilized rat thyroid cells (FRTL5). In this system, the muscarinic agonist carbachol inhibited phospholipase C, as indicated by the decrease in the basal levels of inositol 1,4,5-trisphosphate as well as by the reduced adrenergic stimulation of phosphoinositol accumulation, which was paralleled by a fall in the cytosolic Ca2+ levels. This inhibition involved an M2 muscarinic receptor because it was abolished by atropine but not by the M1 antagonist pirenzepine. Cells pretreated with pertussis toxin were not responsive to carbachol, indicating the involvement of a guanine nucleotide-binding protein in this inhibitory process. This possibility was further evaluated in permeabilized cells, where the carbachol inhibition was shown to be completely dependent on GTP. Known second messengers were not involved in this inhibitory process since Ca2+, cAMP, and activators of protein kinases were not able to mimic or prevent the carbachol effect either in intact or in permeabilized FRTL5 cells. In this system, the phospholipases C and A2 are coupled to two classes of muscarinic receptors that display a different sensitivity to pertussis toxin. The carbachol inhibitory effect occurred under conditions that prevented activation of phospholipase A2, excluding a role of the arachidonic acid metabolism in this process. Taken together these data provide the strongest support to date that an inhibitory guanine nucleotide-binding protein sensitive to pertussis toxin can directly mediate receptor-induced inhibition of phospholipase C.

authors

Bizzarri C,Di Girolamo M,D'Orazio MC,Corda D

doi

10.1073/pnas.87.12.4889

subject

Has Abstract

pub_date

1990-06-01 00:00:00

pages

4889-93

issue

12

eissn

0027-8424

issn

1091-6490

journal_volume

87

pub_type

杂志文章
  • Comparison of nucleotide interactions in water, proteins, and vacuum: model for DNA polymerase fidelity.

    abstract::We propose a model for DNA polymerase fidelity in which free energy differences, delta delta G, between matched and mismatched nucleotides are magnified at the enzyme's active site. Both hydrogen bonding and stacking components of the interaction energy are amplified, with the most profound effect being on the magnitu...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.6.1559

    authors: Petruska J,Sowers LC,Goodman MF

    更新日期:1986-03-01 00:00:00

  • Navigating transformations in governance of Chilean marine coastal resources.

    abstract::Marine ecosystems are in decline. New transformational changes in governance are urgently required to cope with overfishing, pollution, global changes, and other drivers of degradation. Here we explore social, political, and ecological aspects of a transformation in governance of Chile's coastal marine resources, from...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1012021107

    authors: Gelcich S,Hughes TP,Olsson P,Folke C,Defeo O,Fernández M,Foale S,Gunderson LH,Rodríguez-Sickert C,Scheffer M,Steneck RS,Castilla JC

    更新日期:2010-09-28 00:00:00

  • An accumulator model for spontaneous neural activity prior to self-initiated movement.

    abstract::A gradual buildup of neuronal activity known as the "readiness potential" reliably precedes voluntary self-initiated movements, in the average time locked to movement onset. This buildup is presumed to reflect the final stages of planning and preparation for movement. Here we present a different interpretation of the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1210467109

    authors: Schurger A,Sitt JD,Dehaene S

    更新日期:2012-10-16 00:00:00

  • Muller cells are living optical fibers in the vertebrate retina.

    abstract::Although biological cells are mostly transparent, they are phase objects that differ in shape and refractive index. Any image that is projected through layers of randomly oriented cells will normally be distorted by refraction, reflection, and scattering. Counterintuitively, the retina of the vertebrate eye is inverte...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0611180104

    authors: Franze K,Grosche J,Skatchkov SN,Schinkinger S,Foja C,Schild D,Uckermann O,Travis K,Reichenbach A,Guck J

    更新日期:2007-05-15 00:00:00

  • Understanding the mechanical response of double-stranded DNA and RNA under constant stretching forces using all-atom molecular dynamics.

    abstract::Multiple biological processes involve the stretching of nucleic acids (NAs). Stretching forces induce local changes in the molecule structure, inhibiting or promoting the binding of proteins, which ultimately affects their functionality. Understanding how a force induces changes in the structure of NAs at the atomic l...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1705642114

    authors: Marin-Gonzalez A,Vilhena JG,Perez R,Moreno-Herrero F

    更新日期:2017-07-03 00:00:00

  • Enzyme null alleles in natural populations of Drosophila melanogaster: Frequencies in a North Carolina population.

    abstract::A Raleigh, NC, population of Drosophila melanogaster was sampled for the presence of enzyme null alleles at 25 loci. No nulls were found at any of five X-linked loci. Nulls were recovered at 13 of 20 autosomal loci; the weighted mean frequency for all 20 autosomal loci was estimated to be 0.0025. A consideration of th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.77.2.1091

    authors: Voelker RA,Langley CH,Brown AJ,Ohnishi S,Dickson B,Montgomery E,Smith SC

    更新日期:1980-02-01 00:00:00

  • Human type I procollagen genes are located on different chromosomes.

    abstract::A recombinant plasmid containing sequences complementary to human pro-alpha l(I) collagen mRNA was used for the chromosomal assignment of the pro-alpha l(I) collagen gene. Restriction endonuclease analysis of DNA from mouse-human and Chinese hamster-human somatic cell hybrids revealed cosegregation with human chromoso...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.21.6627

    authors: Huerre C,Junien C,Weil D,Chu ML,Morabito M,Van Cong N,Myers JC,Foubert C,Gross MS,Prockop DJ,Boué A,Kaplan JC,de la Chapelle A,Ramirez F

    更新日期:1982-11-01 00:00:00

  • Chemical synthesis and X-ray structure of a heterochiral {D-protein antagonist plus vascular endothelial growth factor} protein complex by racemic crystallography.

    abstract::Total chemical synthesis was used to prepare the mirror image (D-protein) form of the angiogenic protein vascular endothelial growth factor (VEGF-A). Phage display against D-VEGF-A was used to screen designed libraries based on a unique small protein scaffold in order to identify a high affinity ligand. Chemically syn...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1210483109

    authors: Mandal K,Uppalapati M,Ault-Riché D,Kenney J,Lowitz J,Sidhu SS,Kent SB

    更新日期:2012-09-11 00:00:00

  • Insect herbivory, plant defense, and early Cenozoic climate change.

    abstract::Insect damage on fossil leaves from the Central Rocky Mountains, United States, documents the response of herbivores to changing regional climates and vegetation during the late Paleocene (humid, warm temperate to subtropical, predominantly deciduous), early Eocene (humid subtropical, mixed deciduous and evergreen), a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.111069498

    authors: Wilf P,Labandeira CC,Johnson KR,Coley PD,Cutter AD

    更新日期:2001-05-22 00:00:00

  • Molecular cloning of a full-length cDNA for human alcohol dehydrogenase.

    abstract::We have cloned a full-length cDNA coding for human alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) from a human liver cDNA library constructed in phage lambda gt11. The library was screened by using a rabbit antibody against human ADH as a first probe, by the modified method of Young and Davis [Yo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.9.2703

    authors: Ikuta T,Fujiyoshi T,Kurachi K,Yoshida A

    更新日期:1985-05-01 00:00:00

  • Overcoming design and development challenges in agent-based modeling using ASCAPE.

    abstract::The ASCAPE agent-based modeling environment greatly eases the task of designing and investigating agent-based models. However, effective design can still require a relatively deep knowledge of programming and agent-based modeling. This issue has almost certainly slowed the adoption of agent-based modeling approaches t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.082081199

    authors: Inchiosa ME,Parker MT

    更新日期:2002-05-14 00:00:00

  • Two proteolytic pathways regulate DNA repair by cotargeting the Mgt1 alkylguanine transferase.

    abstract::O(6)-methylguanine (O(6)meG) and related modifications of guanine in double-stranded DNA are functionally severe lesions that can be produced by many alkylating agents, including N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a potent carcinogen. O(6)meG is repaired through its demethylation by the O(6)-alkylguanine-DNA...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0812316106

    authors: Hwang CS,Shemorry A,Varshavsky A

    更新日期:2009-02-17 00:00:00

  • Pore-pressure diffusion, enhanced by poroelastic stresses, controls induced seismicity in Oklahoma.

    abstract::Induced seismicity linked to geothermal resource exploitation, hydraulic fracturing, and wastewater disposal is evolving into a global issue because of the increasing energy demand. Moderate to large induced earthquakes, causing widespread hazards, are often related to fluid injection into deep permeable formations th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1819225116

    authors: Zhai G,Shirzaei M,Manga M,Chen X

    更新日期:2019-08-13 00:00:00

  • Contraction characteristics and ATPase activity of skeletal muscle fibers in the presence of antibody to myosin subfragment 2.

    abstract::To investigate the role of the myosin hinge region in muscle contraction, we examined the contraction characteristics and Mg-ATPase activity of glycerinated muscle fibers prepared from rabbit psoas in the presence and absence of polyclonal antibody directed against the subfragment 2 (S-2) region of myosin. The antibod...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.13.6134

    authors: Sugi H,Kobayashi T,Gross T,Noguchi K,Karr T,Harrington WF

    更新日期:1992-07-01 00:00:00

  • Conformational landscape of cytochrome c folding studied by microsecond-resolved small-angle x-ray scattering.

    abstract::To investigate protein folding dynamics in terms of compactness, we developed a continuous-flow mixing device to make small-angle x-ray scattering measurements with the time resolution of 160 micros and characterized the radius of gyration (R(g)) of two folding intermediates of cytochrome c (cyt c). The early intermed...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.012458999

    authors: Akiyama S,Takahashi S,Kimura T,Ishimori K,Morishima I,Nishikawa Y,Fujisawa T

    更新日期:2002-02-05 00:00:00

  • Dorsal periaqueductal gray-amygdala pathway conveys both innate and learned fear responses in rats.

    abstract::The periaqueductal gray (PAG) and amygdala are known to be important for defensive responses, and many contemporary fear-conditioning models present the PAG as downstream of the amygdala, directing the appropriate behavior (i.e., freezing or fleeing). However, empirical studies of this circuitry are inconsistent and w...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1310845110

    authors: Kim EJ,Horovitz O,Pellman BA,Tan LM,Li Q,Richter-Levin G,Kim JJ

    更新日期:2013-09-03 00:00:00

  • Long-term reconstitution of the mouse hematopoietic system by embryonic stem cell-derived fetal liver.

    abstract::Murine embryonic stem (ES) cells are permanent blastocyst-derived cell lines capable of contributing to a wide variety of tissues, including the germ line, after injection into host blastocysts. Recently, we have shown that ES cells can produce all of the cells of the developing fetus after aggregation with developmen...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.17.7514

    authors: Forrester LM,Bernstein A,Rossant J,Nagy A

    更新日期:1991-09-01 00:00:00

  • Expression of a human acetylcholinesterase promoter-reporter construct in developing neuromuscular junctions of Xenopus embryos.

    abstract::We have employed Xenopus embryos to express human acetylcholinesterase (AcChoEase; EC 3.1.1.7) in developing synapses. Transcription of AcChoEase mRNA was driven by a 2.2-kb sequence upstream from the initiator AUG in the ACHE gene encoding AcChoEase, with multiple potential sites for binding universal and tissue-spec...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.6.2471

    authors: Ben Aziz-Aloya R,Seidman S,Timberg R,Sternfeld M,Zakut H,Soreq H

    更新日期:1993-03-15 00:00:00

  • Leveraging scientific credibility about Arctic sea ice trends in a polarized political environment.

    abstract::This work argues that, in a polarized environment, scientists can minimize the likelihood that the audience's biased processing will lead to rejection of their message if they not only eschew advocacy but also, convey that they are sharers of knowledge faithful to science's way of knowing and respectful of the audienc...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1320868111

    authors: Jamieson KH,Hardy BW

    更新日期:2014-09-16 00:00:00

  • Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Δ32 mutation confers resistance to HIV infection.

    abstract::Individuals homozygous for the C-C chemokine receptor type 5 gene with 32-bp deletions (CCR5Δ32) are resistant to HIV-1 infection. In this study, we generated induced pluripotent stem cells (iPSCs) homozygous for the naturally occurring CCR5Δ32 mutation through genome editing of wild-type iPSCs using a combination of ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1407473111

    authors: Ye L,Wang J,Beyer AI,Teque F,Cradick TJ,Qi Z,Chang JC,Bao G,Muench MO,Yu J,Levy JA,Kan YW

    更新日期:2014-07-01 00:00:00

  • Evidence for abrupt speciation in a classic case of gradual evolution.

    abstract::In contrast with speciation in terrestrial organisms, marine plankton frequently display gradual morphological change without lineage division (e.g., phyletic gradualism or gradual evolution), which has raised the possibility that a different mode of evolution dominates within pelagic environments. Here, we reexamine ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 历史文章,杂志文章

    doi:10.1073/pnas.0902887106

    authors: Hull PM,Norris RD

    更新日期:2009-12-15 00:00:00

  • Ultrahigh-throughput screening in drop-based microfluidics for directed evolution.

    abstract::The explosive growth in our knowledge of genomes, proteomes, and metabolomes is driving ever-increasing fundamental understanding of the biochemistry of life, enabling qualitatively new studies of complex biological systems and their evolution. This knowledge also drives modern biotechnologies, such as molecular engin...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0910781107

    authors: Agresti JJ,Antipov E,Abate AR,Ahn K,Rowat AC,Baret JC,Marquez M,Klibanov AM,Griffiths AD,Weitz DA

    更新日期:2010-03-02 00:00:00

  • Retinoblastoma gene product as a downstream target for a ceramide-dependent pathway of growth arrest.

    abstract::Ceramide, a lipid mediator, has been most closely associated with antiproliferative activities. In this study, we examine the mechanism by which ceramide induces growth suppression and the role of the retinoblastoma gene product (Rb) in this process. Withdrawal of serum from the serum-dependent MOLT-4 cells resulted i...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.5.1347

    authors: Dbaibo GS,Pushkareva MY,Jayadev S,Schwarz JK,Horowitz JM,Obeid LM,Hannun YA

    更新日期:1995-02-28 00:00:00

  • The active form of the steroidogenic acute regulatory protein, StAR, appears to be a molten globule.

    abstract::The steroidogenic acute regulatory protein (StAR) increases the movement of cholesterol from the outer to the inner membrane of adrenal and gonadal mitochondria, thus providing the substrate for steroid hormone biosynthesis. Deletion of 62 amino-terminal aa produces a cytoplasmic form of StAR (N-62 StAR) that lacks th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.13.7250

    authors: Bose HS,Whittal RM,Baldwin MA,Miller WL

    更新日期:1999-06-22 00:00:00

  • Structure-based design of an osteoclast-selective, nonpeptide src homology 2 inhibitor with in vivo antiresorptive activity.

    abstract::Targeted disruption of the pp60(src) (Src) gene has implicated this tyrosine kinase in osteoclast-mediated bone resorption and as a therapeutic target for the treatment of osteoporosis and other bone-related diseases. Herein we describe the discovery of a nonpeptide inhibitor (AP22408) of Src that demonstrates in vivo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.97.17.9373

    authors: Shakespeare W,Yang M,Bohacek R,Cerasoli F,Stebbins K,Sundaramoorthi R,Azimioara M,Vu C,Pradeepan S,Metcalf C 3rd,Haraldson C,Merry T,Dalgarno D,Narula S,Hatada M,Lu X,van Schravendijk MR,Adams S,Violette S,Smith J,

    更新日期:2000-08-15 00:00:00

  • Complex network analysis of free-energy landscapes.

    abstract::The kinetics of biomolecular isomerization processes, such as protein folding, is governed by a free-energy surface of high dimensionality and complexity. As an alternative to projections into one or two dimensions, the free-energy surface can be mapped into a weighted network where nodes and links are configurations ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0608099104

    authors: Gfeller D,De Los Rios P,Caflisch A,Rao F

    更新日期:2007-02-06 00:00:00

  • Primate lentiviral virion infectivity factors are substrate receptors that assemble with cullin 5-E3 ligase through a HCCH motif to suppress APOBEC3G.

    abstract::Cullin-Ring E3 ubiquitin ligases target substrates for ubiquitin-dependent, proteasome-mediated degradation and regulate critical cellular processes. These cullins assemble with cellular substrate receptor proteins through specific adaptor molecules. F-box- and BC-box-containing receptors use Skp1, ElonginB, and Elong...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0502440102

    authors: Luo K,Xiao Z,Ehrlich E,Yu Y,Liu B,Zheng S,Yu XF

    更新日期:2005-08-09 00:00:00

  • Dynamics of shear-induced ATP release from red blood cells.

    abstract::Adenosine triphosphate (ATP) is a regulatory molecule for many cell functions, both for intracellular and, perhaps less well known, extracellular functions. An important example of the latter involves red blood cells (RBCs), which help regulate blood pressure by releasing ATP as a vasodilatory signaling molecule in re...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0805779105

    authors: Wan J,Ristenpart WD,Stone HA

    更新日期:2008-10-28 00:00:00

  • Cytolytic and antibacterial activity of synthetic peptides derived from amoebapore, the pore-forming peptide of Entamoeba histolytica.

    abstract::The pore-forming peptide amoebapore is considered part of the cytolytic armament of pathogenic Entamoeba histolytica. Amoebapore is composed of 77 amino acid residues arranged in four alpha-helical domains. For structure-function analysis, synthetic peptides were constructed corresponding to these four domains: H1 (re...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.7.2602

    authors: Leippe M,Andrä J,Müller-Eberhard HJ

    更新日期:1994-03-29 00:00:00

  • Structure of trigger factor binding domain in biologically homologous complex with eubacterial ribosome reveals its chaperone action.

    abstract::Trigger factor (TF), the first chaperone in eubacteria to encounter the emerging nascent chain, binds to the large ribosomal subunit in the vicinity of the protein exit tunnel opening and forms a sheltered folding space. Here, we present the 3.5-A crystal structure of the physiological complex of the large ribosomal s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0505581102

    authors: Baram D,Pyetan E,Sittner A,Auerbach-Nevo T,Bashan A,Yonath A

    更新日期:2005-08-23 00:00:00