Monoclonal antibodies to the human insulin receptor block insulin binding and inhibit insulin action.

Abstract:

:Antibodies to the insulin receptor were prepared in BALB/c mice by immunization with IM-9 human lymphocytes, a cell type that has a large number of plasma membrane insulin receptors. The spleens of these mice were then removed, and their lymphocytes were fused to a mouse myeloma cell line, FO cells. After screening over 1,200 resulting hybrids, one stable hybrid was obtained that produced IgG1 antibodies directed towards the insulin receptor. This antibody blocked 125I-labeled insulin binding to its receptor by more than 90% in three human tissues: IM-9 cultured lymphocytes, freshly isolated adipocytes, and placenta membranes. In contrast, the antibody did not inhibit insulin binding to rat adipocytes and rat liver plasma membranes, suggesting that the antibody was species specific. In IM-9 cells, which had their proteins prelabeled with [35S]methionine, the antibody precipitated two polypeptides with molecular weights of 135,000 and 95,000; these molecular weights are identical to those previously identified as the alpha and beta subunits of the insulin receptor. The monoclonal antibody inhibited the actions of insulin on both human adipocytes and fibroblasts, suggesting that the antibody was an antagonist of insulin action. The present studies suggest, therefore, that monoclonal antibodies to the insulin receptor may provide new insights into the structure of the insulin receptor and its interaction with insulin.

authors

Roth RA,Cassell DJ,Wong KY,Maddux BA,Goldfine ID

doi

10.1073/pnas.79.23.7312

subject

Has Abstract

pub_date

1982-12-01 00:00:00

pages

7312-6

issue

23

eissn

0027-8424

issn

1091-6490

journal_volume

79

pub_type

杂志文章
  • Supermarket revolution in Asia and emerging development strategies to include small farmers.

    abstract::A "supermarket revolution" has occurred in developing countries in the past 2 decades. We focus on three specific issues that reflect the impact of this revolution, particularly in Asia: continuity in transformation, innovation in transformation, and unique development strategies. First, the record shows that the rapi...

    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.1003160108

    authors: Reardon T,Timmer CP,Minten B

    更新日期:2012-07-31 00:00:00

  • Visualizing the formation of the Kondo lattice and the hidden order in URu(2)Si(2).

    abstract::Heavy electronic states originating from the f atomic orbitals underlie a rich variety of quantum phases of matter. We use atomic scale imaging and spectroscopy with the scanning tunneling microscope to examine the novel electronic states that emerge from the uranium f states in URu(2)Si(2). We find that, as the tempe...

    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.1005892107

    authors: Aynajian P,da Silva Neto EH,Parker CV,Huang Y,Pasupathy A,Mydosh J,Yazdani A

    更新日期:2010-06-08 00:00:00

  • ChIP-on-chip significance analysis reveals large-scale binding and regulation by human transcription factor oncogenes.

    abstract::ChIP-on-chip has emerged as a powerful tool to dissect the complex network of regulatory interactions between transcription factors and their targets. However, most ChIP-on-chip analysis methods use conservative approaches aimed at minimizing false-positive transcription factor targets. We present a model with improve...

    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.0806445106

    authors: Margolin AA,Palomero T,Sumazin P,Califano A,Ferrando AA,Stolovitzky G

    更新日期:2009-01-06 00:00:00

  • Nature of ground and electronic excited states of higher acenes.

    abstract::Higher acenes have drawn much attention as promising organic semiconductors with versatile electronic properties. However, the nature of their ground state and electronic excited states is still not fully clear. Their unusual chemical reactivity and instability are the main obstacles for experimental studies, and 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.1606021113

    authors: Yang Y,Davidson ER,Yang W

    更新日期:2016-08-30 00:00:00

  • Analysis of HIV-1 env gene sequences reveals evidence for a low effective number in the viral population.

    abstract::Selection is usually considered to be the dominant force controlling viral variation; the large population sizes suggest that deterministic population genetic models are appropriate. To investigate their validity for HIV, samples of env gene sequences were tested for departure from neutrality because of mutation-selec...

    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.94.5.1862

    authors: Brown AJ

    更新日期:1997-03-04 00:00:00

  • Probing the Saccharomyces cerevisiae centromeric DNA (CEN DNA)-binding factor 3 (CBF3) kinetochore complex by using atomic force microscopy.

    abstract::Yeast centromeric DNA (CEN DNA) binding factor 3 (CBF3) is a multisubunit protein complex that binds to the essential CDEIII element in CEN DNA. The four CBF3 proteins are required for accurate chromosome segregation and are considered to be core components of the yeast kinetochore. We have examined the structure of 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.96.7.3757

    authors: Pietrasanta LI,Thrower D,Hsieh W,Rao S,Stemmann O,Lechner J,Carbon J,Hansma H

    更新日期:1999-03-30 00:00:00

  • Expanded subgenomic mRNA transcriptome and coding capacity of a nidovirus.

    abstract::Members of the order Nidovirales express their structural protein ORFs from a nested set of 3' subgenomic mRNAs (sg mRNAs), and for most of these ORFs, a single genomic transcription regulatory sequence (TRS) was identified. Nine TRSs were previously reported for the arterivirus Simian hemorrhagic fever virus (SHFV). ...

    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.1706696114

    authors: Di H,Madden JC Jr,Morantz EK,Tang HY,Graham RL,Baric RS,Brinton MA

    更新日期:2017-10-17 00:00:00

  • An archaeal primase functions as a nanoscale caliper to define primer length.

    abstract::The cellular replicative DNA polymerases cannot initiate DNA synthesis without a priming 3' OH. During DNA replication, this is supplied in the context of a short RNA primer molecule synthesized by DNA primase. The primase of archaea and eukaryotes, despite having varying subunit compositions, share sequence and struc...

    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.1806351115

    authors: Yan J,Holzer S,Pellegrini L,Bell SD

    更新日期:2018-06-26 00:00:00

  • MAL6 of Saccharomyces: a complex genetic locus containing three genes required for maltose fermentation.

    abstract::The MAL6 locus is one of five closely related unlinked loci, any one of which is sufficient for fermentation of maltose in Saccharomyces. Previous genetic analysis indicated that this locus is defined by two complementation groups, MALp and MALg. MALp reportedly is a regulatory gene required for inducible synthesis 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.81.9.2811

    authors: Needleman RB,Kaback DB,Dubin RA,Perkins EL,Rosenberg NG,Sutherland KA,Forrest DB,Michels CA

    更新日期:1984-05-01 00:00:00

  • Evidence for a nonprolactin, non-growth-hormone mammary mitogen in the human pituitary gland.

    abstract::To determine whether the human pituitary contains a previously unidentified, nonprolactin (non-hPRL), non-growth-hormone (non-hGH) factor capable of stimulating mammary development, we tested the effects of whole human pituitary extract (hPE) and pituitary extracts depleted of hPRL and hGH ("stripped hPE") in hypophys...

    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.84.22.8110

    authors: Newman CB,Cosby H,Friesen HG,Feldman M,Cooper P,De Crescito V,Pilon M,Kleinberg DL

    更新日期:1987-11-01 00:00:00

  • Sphingosine 1-phosphate receptor modulation suppresses pathogenic astrocyte activation and chronic progressive CNS inflammation.

    abstract::Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the CNS that causes disability in young adults as a result of the irreversible accumulation of neurological deficits. Although there are potent disease-modifying agents for its initial relapsing-remitting phase, these therapies show limited...

    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.1615413114

    authors: Rothhammer V,Kenison JE,Tjon E,Takenaka MC,de Lima KA,Borucki DM,Chao CC,Wilz A,Blain M,Healy L,Antel J,Quintana FJ

    更新日期:2017-02-21 00:00:00

  • Discs large 1 controls daughter-cell polarity after cytokinesis in vertebrate morphogenesis.

    abstract::Vertebrate embryogenesis and organogenesis are driven by cell biological processes, ranging from mitosis and migration to changes in cell size and polarity, but their control and causal relationships are not fully defined. Here, we use the developing limb skeleton to better define the relationships between mitosis and...

    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.1713959115

    authors: Li Y,Junge JA,Arnesano C,Gross GG,Miner JH,Moats R,Roberts RW,Arnold DB,Fraser SE

    更新日期:2018-11-13 00:00:00

  • Differential utilization of leucyl-tRNAs by Escherichia coli.

    abstract::The utilization of the isoaccepting species of leucyl-tRNA in protein synthesis has been examined in E. coli. Two minor leucyl-tRNA species, isoacceptors tRNA3Leu and tRNA4Leu, are the predominant species found bound to ribosomes during exponential growth in minimal medium. In rich medium, an increased proportion of 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.74.4.1393

    authors: Holmes WM,Goldman E,Miner TA,Hatfield GW

    更新日期:1977-04-01 00:00:00

  • Valproic acid interactions with the NavMs voltage-gated sodium channel.

    abstract::Valproic acid (VPA) is an anticonvulsant drug that is also used to treat migraines and bipolar disorder. Its proposed biological targets include human voltage-gated sodium channels, among other membrane proteins. We used the prokaryotic NavMs sodium channel, which has been shown to be a good exemplar for drug binding ...

    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.1909696116

    authors: Zanatta G,Sula A,Miles AJ,Ng LCT,Torella R,Pryde DC,DeCaen PG,Wallace BA

    更新日期:2019-12-10 00:00:00

  • Tumor regionality in the mouse intestine reflects the mechanism of loss of Apc function.

    abstract::Inherited colorectal cancer syndromes in humans exhibit regional specificity for tumor formation. By using mice with germline mutations in the adenomatous polyposis coli gene (Apc) and/or DNA mismatch repair genes, we have analyzed the genetic control of tumor regionality in the mouse small intestine. In C57BL/6 mice ...

    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.0403338101

    authors: Haigis KM,Hoff PD,White A,Shoemaker AR,Halberg RB,Dove WF

    更新日期:2004-06-29 00:00:00

  • Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6.

    abstract::Mammalian CLC proteins function as Cl(-) channels or as electrogenic Cl(-)/H(+) exchangers and are present in the plasma membrane and intracellular vesicles. We now show that the ClC-6 protein is almost exclusively expressed in neurons of the central and peripheral nervous systems, with a particularly high expression ...

    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.0606137103

    authors: Poët M,Kornak U,Schweizer M,Zdebik AA,Scheel O,Hoelter S,Wurst W,Schmitt A,Fuhrmann JC,Planells-Cases R,Mole SE,Hübner CA,Jentsch TJ

    更新日期:2006-09-12 00:00:00

  • Neoplastic transformation of human diploid fibroblast cells by chemical carcinogens.

    abstract::Cultured fibroblast cells derived from a skin biopsy sample taken from normal human adult were exposed to a potent carcinogen, 4-nitroquinoline 1-oxide. Alterations of cell growth pattern such as higher density and piling up of cells were noticed in some fractions of cultures that were successively subcultured after n...

    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.75.3.1334

    authors: Kakunaga T

    更新日期:1978-03-01 00:00:00

  • Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine.

    abstract::Stress-induced structural remodeling in the adult hippocampus, involving debranching and shortening of dendrites and suppression of neurogenesis, provides a cellular basis for understanding the impairment of neural plasticity in the human hippocampus in depressive illness. Accordingly, reversal of structural remodelin...

    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.211427898

    authors: Czéh B,Michaelis T,Watanabe T,Frahm J,de Biurrun G,van Kampen M,Bartolomucci A,Fuchs E

    更新日期:2001-10-23 00:00:00

  • Conformational properties of the acetylcholine receptor as revealed by studies with constrained depolarizing ligands.

    abstract::Conformational aspects of the acetylcholine receptor (AcChoR) of Electrophorus electricus have been examined by studies of its interaction with structurally related, constrained aromatic bis quaternary compounds. Among the compounds synthesized was 3,3'-bis[alpha-(trimethylammonium)-methyl]azobenzene dibromide (3,3'-b...

    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.76.1.256

    authors: Wassermann NH,Bartels E,Erlanger BF

    更新日期:1979-01-01 00:00:00

  • The DNA damage response in DNA-dependent protein kinase-deficient SCID mouse cells: replication protein A hyperphosphorylation and p53 induction.

    abstract::Severe combined immunodeficient (SCID) mice display an increased sensitivity to ionizing radiation compared with the parental, C.B-17, strain due to a deficiency in DNA double-strand break repair. The catalytic subunit of DNA-dependent protein kinase (DNA-PKCS) has previously been identified as a strong candidate for ...

    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.93.24.13825

    authors: Fried LM,Koumenis C,Peterson SR,Green SL,van Zijl P,Allalunis-Turner J,Chen DJ,Fishel R,Giaccia AJ,Brown JM,Kirchgessner CU

    更新日期:1996-11-26 00:00:00

  • Development of hippocampal mossy fiber synaptic outputs by new neurons in the adult brain.

    abstract::New neurons are continuously generated in restricted regions of the adult mammalian brain. Although these adult-born neurons have been shown to receive synaptic inputs, little is known about their synaptic outputs. Using retrovirus-mediated birth-dating and labeling in combination with serial section electron microsco...

    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.0806658105

    authors: Faulkner RL,Jang MH,Liu XB,Duan X,Sailor KA,Kim JY,Ge S,Jones EG,Ming GL,Song H,Cheng HJ

    更新日期:2008-09-16 00:00:00

  • Phosphorylation-independent dual-site binding of the FHA domain of KIF13 mediates phosphoinositide transport via centaurin alpha1.

    abstract::Phosphatidylinositol 3,4,5-triphosphate (PIP3) plays a key role in neuronal polarization and axon formation. PIP3-containing vesicles are transported to axon tips by the kinesin KIF13B via an adaptor protein, centaurin α1 (CENTA1). KIF13B interacts with CENTA1 through its forkhead-associated (FHA) domain. We solved 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.1009008107

    authors: Tong Y,Tempel W,Wang H,Yamada K,Shen L,Senisterra GA,MacKenzie F,Chishti AH,Park HW

    更新日期:2010-11-23 00:00:00

  • Human biliverdin reductase is an ERK activator; hBVR is an ERK nuclear transporter and is required for MAPK signaling.

    abstract::Activation of the MEK/ERK/Elk-signaling cascade is a mechanism for relaying mitogenic and stress stimuli for gene activation. MEK1 is the proximate kinase for activation of ERK1/2, and nuclear targeting of ERK1/2 is obligatory for Elk1 transcriptional activity. Human biliverdin reductase (hBVR) is a recently described...

    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.0800750105

    authors: Lerner-Marmarosh N,Miralem T,Gibbs PE,Maines MD

    更新日期:2008-05-13 00:00:00

  • The retinal chromophore/chloride ion pair: structure of the photoisomerization path and interplay of charge transfer and covalent states.

    abstract::Ab initio multi-reference second-order perturbation theory computations are used to explore the photochemical behavior of two ion pairs constituted by a chloride counterion interacting with either a rhodopsin or bacteriorhodopsin chromophore model (i.e., the 4-cis-gamma-methylnona-2,4,6,8-tetraeniminium and all-trans-...

    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.0408723102

    authors: Cembran A,Bernardi F,Olivucci M,Garavelli M

    更新日期:2005-05-03 00:00:00

  • Evolution of resistance in vitro reveals mechanisms of artemisinin activity in Toxoplasma gondii.

    abstract::Artemisinins are effective against a variety of parasites and provide the first line of treatment for malaria. Laboratory studies have identified several mechanisms for artemisinin resistance in Plasmodium falciparum, including mutations in Kelch13 that are associated with delayed clearance in some clinical isolates, ...

    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.1914732116

    authors: Rosenberg A,Luth MR,Winzeler EA,Behnke M,Sibley LD

    更新日期:2019-12-05 00:00:00

  • Human brain glial cells synthesize thrombospondin.

    abstract::Thrombospondin, a 450-kDa multinodular glycoprotein with lectin-type activity, is found in human platelets, endothelial cells, fibroblasts, smooth muscle cells, monocytes, and granular pneumocytes. Thrombospondin interacts with heparin, fibrinogen, fibronectin, collagen, histidine-rich glycoprotein, and plasminogen. R...

    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.83.9.2904

    authors: Asch AS,Leung LL,Shapiro J,Nachman RL

    更新日期:1986-05-01 00:00:00

  • Extreme rainfall activity in the Australian tropics reflects changes in the El Niño/Southern Oscillation over the last two millennia.

    abstract::Assessing temporal variability in extreme rainfall events before the historical era is complicated by the sparsity of long-term "direct" storm proxies. Here we present a 2,200-y-long, accurate, and precisely dated record of cave flooding events from the northwest Australian tropics that we interpret, based on an integ...

    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.1422270112

    authors: Denniston RF,Villarini G,Gonzales AN,Wyrwoll KH,Polyak VJ,Ummenhofer CC,Lachniet MS,Wanamaker AD Jr,Humphreys WF,Woods D,Cugley J

    更新日期:2015-04-14 00:00:00

  • DNase I-hypersensitive sites in the chromatin of immunoglobulin kappa light chain genes.

    abstract::We have used DNase I as a probe to examine the chromatin structure of mouse immunoglobulin kappa light chain genes in rearranged and unrearranged chromosomes--i.e., in nuclei from myeloma cells and from brain and liver cells. Tissue-specific DNase I-hypersensitive sites are observed 0.7 and 1.7 kilobases upstream 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.80.9.2427

    authors: Chung SY,Folsom V,Wooley J

    更新日期:1983-05-01 00:00:00

  • Membrane orientation of the FMO antenna protein from Chlorobaculum tepidum as determined by mass spectrometry-based footprinting.

    abstract::The high excitation energy-transfer efficiency demanded in photosynthetic organisms relies on the optimal pigment-protein binding orientation in the individual protein complexes and also on the overall architecture of the photosystem. In green sulfur bacteria, the membrane-attached Fenna-Matthews-Olson (FMO) antenna p...

    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.0901691106

    authors: Wen J,Zhang H,Gross ML,Blankenship RE

    更新日期:2009-04-14 00:00:00

  • A simple generative model of collective online behavior.

    abstract::Human activities increasingly take place in online environments, providing novel opportunities for relating individual behaviors to population-level outcomes. In this paper, we introduce a simple generative model for the collective behavior of millions of social networking site users who are deciding between different...

    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.1313895111

    authors: Gleeson JP,Cellai D,Onnela JP,Porter MA,Reed-Tsochas F

    更新日期:2014-07-22 00:00:00