Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein.


:Since the discovery of insulin nearly 70 years ago, there has been no problem more fundamental to diabetes research than understanding how insulin works at the cellular level. Insulin binds to the alpha subunit of the insulin receptor which activates the tyrosine kinase in the beta subunit, but the molecular events linking the receptor kinase to insulin-sensitive enzymes and transport processes are unknown. Our discovery that insulin stimulates tyrosine phosphorylation of a protein of relative molecular mass between 165,000 and 185,000, collectively called pp185, showed that the insulin receptor kinase has specific cellular substrates. The pp185 is a minor cytoplasmic phosphoprotein found in most cells and tissues; its phosphorylation is decreased in cells expressing mutant receptors defective in signalling. We have now cloned IRS-1, which encodes a component of the pp185 band. IRS-1 contains over ten potential tyrosine phosphorylation sites, six of which are in Tyr-Met-X-Met motifs. During insulin stimulation, the IRS-1 protein undergoes tyrosine phosphorylation and binds phosphatidylinositol 3-kinase, suggesting that IRS-1 acts as a multisite 'docking' protein to bind signal-transducing molecules containing Src-homology 2 and Src-homology-3 domains. Thus IRS-1 may link the insulin receptor kinase and enzymes regulating cellular growth and metabolism.






Sun XJ,Rothenberg P,Kahn CR,Backer JM,Araki E,Wilden PA,Cahill DA,Goldstein BJ,White MF





Has Abstract


1991-07-04 00:00:00














  • Bone marrow cells give rise to distinct cell clones within the thymus.

    abstract::The thymus is the major, if not the sole site of maturation of T lymphocytes from their haematopoietic precursors. During embryonic life (at a few well-defined intervals, at least in birds) the thymus receives thymus-homing haematopoietic precursors that give rise to antigen-specific functional T lymphocytes. Although...


    pub_type: 杂志文章


    authors: Ezine S,Weissman IL,Rouse RV

    更新日期:1984-06-14 00:00:00

  • Inhibition of monoamine oxidase B in the brains of smokers.

    abstract::The massive health problem associated with cigarette smoking is exacerbated by the addictive properties of tobacco smoke and the limited success of current approaches to cessation of smoking. Yet little is known about the neuropharmacological actions of cigarette smoke that contribute to smoking behaviour, or why smok...


    pub_type: 杂志文章


    authors: Fowler JS,Volkow ND,Wang GJ,Pappas N,Logan J,MacGregor R,Alexoff D,Shea C,Schlyer D,Wolf AP,Warner D,Zezulkova I,Cilento R

    更新日期:1996-02-22 00:00:00

  • Ant navigation: priming of visual route memories.

    abstract::Ants travelling to and fro between their nest and a foraging area may follow stereotyped foodward and homeward routes that are guided by different visual and directional memory sequences. Honeybees are known to fly a feeder-to-hive or hive-to-feeder vector according to whether or not they have recently fed--their feed...


    pub_type: 杂志文章


    authors: Harris RA,Hempel de Ibarra N,Graham P,Collett TS

    更新日期:2005-11-17 00:00:00

  • Ion channels enable electrical communication in bacterial communities.

    abstract::The study of bacterial ion channels has provided fundamental insights into the structural basis of neuronal signalling; however, the native role of ion channels in bacteria has remained elusive. Here we show that ion channels conduct long-range electrical signals within bacterial biofilm communities through spatially ...


    pub_type: 杂志文章


    authors: Prindle A,Liu J,Asally M,Ly S,Garcia-Ojalvo J,Süel GM

    更新日期:2015-11-05 00:00:00

  • Direct estimation of per nucleotide and genomic deleterious mutation rates in Drosophila.

    abstract::Spontaneous mutations are the source of genetic variation required for evolutionary change, and are therefore important for many aspects of evolutionary biology. For example, the divergence between taxa at neutrally evolving sites in the genome is proportional to the per nucleotide mutation rate, u (ref. 1), and this ...


    pub_type: 杂志文章


    authors: Haag-Liautard C,Dorris M,Maside X,Macaskill S,Halligan DL,Houle D,Charlesworth B,Keightley PD

    更新日期:2007-01-04 00:00:00

  • Genetic variants regulating expression levels and isoform diversity during embryogenesis.

    abstract::Embryonic development is driven by tightly regulated patterns of gene expression, despite extensive genetic variation among individuals. Studies of expression quantitative trait loci (eQTL) indicate that genetic variation frequently alters gene expression in cell-culture models and differentiated tissues. However, the...


    pub_type: 杂志文章


    authors: Cannavò E,Koelling N,Harnett D,Garfield D,Casale FP,Ciglar L,Gustafson HE,Viales RR,Marco-Ferreres R,Degner JF,Zhao B,Stegle O,Birney E,Furlong EE

    更新日期:2017-01-19 00:00:00

  • Speciation in a ring.

    abstract::The evolutionary divergence of a single species into two has never been directly observed in nature, primarily because speciation can take a long time to occur. A ring species, in which a chain of intergrading populations encircles a barrier and the terminal forms coexist without interbreeding, provides a situation in...


    pub_type: 杂志文章


    authors: Irwin DE,Bensch S,Price TD

    更新日期:2001-01-18 00:00:00

  • Lentil lectin effectively induces allotransplantation tolerance in mice.

    abstract::The interaction of lectins with carbohydrate receptors on the plasma membrane of eukaryotic cells results in a wide variety of biological effects. One effect which has been extensively studied is the stimulation of lymphocytes to blastogenesis and proliferation. High doses of concanavalin A (Con A) and phytohaemagglut...


    pub_type: 杂志文章


    authors: Hilgert I,Horejsí V,Angelisová P,Kristofová H

    更新日期:1980-03-20 00:00:00

  • Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117.

    abstract::HIV-1 immunotherapy with a combination of first generation monoclonal antibodies was largely ineffective in pre-clinical and clinical settings and was therefore abandoned. However, recently developed single-cell-based antibody cloning methods have uncovered a new generation of far more potent broadly neutralizing anti...


    pub_type: 杂志文章,多中心研究


    authors: Caskey M,Klein F,Lorenzi JC,Seaman MS,West AP Jr,Buckley N,Kremer G,Nogueira L,Braunschweig M,Scheid JF,Horwitz JA,Shimeliovich I,Ben-Avraham S,Witmer-Pack M,Platten M,Lehmann C,Burke LA,Hawthorne T,Gorelick RJ,Walk

    更新日期:2015-06-25 00:00:00

  • Immune defence in bumble-bee offspring.

    abstract::Immune-challenged vertebrate females transfer specific antibodies to their offspring, but this gratuitous immunity cannot operate in invertebrates. Here we show that constitutive immune defence is enhanced in sexual offspring of the bumble-bee Bombus terrestris L. when the parental colony is immune-challenged. Our fin...


    pub_type: 杂志文章


    authors: Moret Y,Schmid-Hempel P

    更新日期:2001-11-29 00:00:00

  • E3 ubiquitin ligase that recognizes sugar chains.

    abstract::N-glycosylation of proteins in the endoplasmic reticulum (ER) has a central role in protein quality control. Here we report that N-glycan serves as a signal for degradation by the Skp1-Cullin1-Fbx2-Roc1 (SCF(Fbx2)) ubiquitin ligase complex. The F-box protein Fbx2 (ref. 4) binds specifically to proteins attached to N-l...


    pub_type: 杂志文章


    authors: Yoshida Y,Chiba T,Tokunaga F,Kawasaki H,Iwai K,Suzuki T,Ito Y,Matsuoka K,Yoshida M,Tanaka K,Tai T

    更新日期:2002-07-25 00:00:00

  • The 2.2 A crystal structure of transducin-alpha complexed with GTP gamma S.

    abstract::The 2.2 A crystal structure of activated rod transducin, Gt alpha.GTP gamma S, shows the bound GTP gamma S molecule occluded deep in a cleft between a domain structurally homologous to small GTPases and a helical domain unique to heterotrimeric G proteins. The structure, when combined with biochemical and genetic stud...


    pub_type: 杂志文章


    authors: Noel JP,Hamm HE,Sigler PB

    更新日期:1993-12-16 00:00:00

  • The rhythm of microbial adaptation.

    abstract::The evolutionary biologist "studies the steps by which the miraculous adaptations so characteristic of every aspect of the organic world have evolved". But the general nature of such adaptive steps is still unclear. Evolution is often thought to be random and dependent on unpredictable events. In this light, one might...


    pub_type: 杂志文章


    authors: Gerrish P

    更新日期:2001-09-20 00:00:00

  • Limitations in the use of actomyosin threads as model contractile systems.

    abstract::Recent studies have suggested that actomyosin threads may provide a useful model for studying the properties of contractile systems. The development of highly sensitive positional feedback transducers has enabled the properties of these threads to be measured reproducibly. Potential applications include such systems a...


    pub_type: 杂志文章


    authors: Altringham JD,Yancey PH,Johnston IA

    更新日期:1980-09-25 00:00:00

  • Control of spatial orientation in a mollusc.

    abstract::The main function of postural nervous mechanisms in different species, from mollusc to man, is to counteract the force of gravity and stabilize body orientation in space. Here we investigate the basic principles of postural control in a simple animal model, the marine mollusc Clione limacina. When swimming, C. limacin...


    pub_type: 杂志文章


    authors: Deliagina TG,Arshavsky YI,Orlovsky GN

    更新日期:1998-05-14 00:00:00

  • The cellular prion protein binds copper in vivo.

    abstract::The normal cellular form of prion protein (PrPC) is a precursor to the pathogenic protease-resistant forms (PrPSc) believed to cause scrapie, bovine spongiform encephalopathy (BSE) and Creutzfeldt-Jakob disease. Its amino terminus contains the octapeptide PHGGGWGQ, which is repeated four times and is among the best-pr...


    pub_type: 杂志文章


    authors: Brown DR,Qin K,Herms JW,Madlung A,Manson J,Strome R,Fraser PE,Kruck T,von Bohlen A,Schulz-Schaeffer W,Giese A,Westaway D,Kretzschmar H

    更新日期:1997-12-18 00:00:00

  • Colombia creates its first science ministry.

    abstract:: ...


    pub_type: 新闻


    authors: Wight AJ

    更新日期:2019-01-01 00:00:00

  • Milestone meetings.

    abstract:: ...


    pub_type: 杂志文章


    authors: Gewin V

    更新日期:2018-12-01 00:00:00

  • Defensin-like polypeptide LUREs are pollen tube attractants secreted from synergid cells.

    abstract::For more than 140 years, pollen tube guidance in flowering plants has been thought to be mediated by chemoattractants derived from target ovules. However, there has been no convincing evidence of any particular molecule being the true attractant that actually controls the navigation of pollen tubes towards ovules. Eme...


    pub_type: 杂志文章


    authors: Okuda S,Tsutsui H,Shiina K,Sprunck S,Takeuchi H,Yui R,Kasahara RD,Hamamura Y,Mizukami A,Susaki D,Kawano N,Sakakibara T,Namiki S,Itoh K,Otsuka K,Matsuzaki M,Nozaki H,Kuroiwa T,Nakano A,Kanaoka MM,Dresselhaus T,Sa

    更新日期:2009-03-19 00:00:00

  • Redox-mediated substrate recognition by Sdp1 defines a new group of tyrosine phosphatases.

    abstract::Reactive oxygen species trigger cellular responses by activation of stress-responsive mitogen-activated protein kinase (MAPK) signalling pathways. Reversal of MAPK activation requires the transcriptional induction of specialized cysteine-based phosphatases that mediate MAPK dephosphorylation. Paradoxically, oxidative ...


    pub_type: 杂志文章


    authors: Fox GC,Shafiq M,Briggs DC,Knowles PP,Collister M,Didmon MJ,Makrantoni V,Dickinson RJ,Hanrahan S,Totty N,Stark MJ,Keyse SM,McDonald NQ

    更新日期:2007-05-24 00:00:00

  • TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells.

    abstract::Therapeutic antibodies that block the programmed death-1 (PD-1)-programmed death-ligand 1 (PD-L1) pathway can induce robust and durable responses in patients with various cancers, including metastatic urothelial cancer. However, these responses only occur in a subset of patients. Elucidating the determinants of respon...


    pub_type: 杂志文章


    authors: Mariathasan S,Turley SJ,Nickles D,Castiglioni A,Yuen K,Wang Y,Kadel EE III,Koeppen H,Astarita JL,Cubas R,Jhunjhunwala S,Banchereau R,Yang Y,Guan Y,Chalouni C,Ziai J,Şenbabaoğlu Y,Santoro S,Sheinson D,Hung J,Giltna

    更新日期:2018-02-22 00:00:00

  • Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.

    abstract::Improvement in the clinical outcome of lung cancer is likely to be achieved by identification of the molecular events that underlie its pathogenesis. Here we show that a small inversion within chromosome 2p results in the formation of a fusion gene comprising portions of the echinoderm microtubule-associated protein-l...


    pub_type: 杂志文章


    authors: Soda M,Choi YL,Enomoto M,Takada S,Yamashita Y,Ishikawa S,Fujiwara S,Watanabe H,Kurashina K,Hatanaka H,Bando M,Ohno S,Ishikawa Y,Aburatani H,Niki T,Sohara Y,Sugiyama Y,Mano H

    更新日期:2007-08-02 00:00:00

  • Mammalian polymerase θ promotes alternative NHEJ and suppresses recombination.

    abstract::The alternative non-homologous end-joining (NHEJ) machinery facilitates several genomic rearrangements, some of which can lead to cellular transformation. This error-prone repair pathway is triggered upon telomere de-protection to promote the formation of deleterious chromosome end-to-end fusions. Using next-generatio...


    pub_type: 杂志文章


    authors: Mateos-Gomez PA,Gong F,Nair N,Miller KM,Lazzerini-Denchi E,Sfeir A

    更新日期:2015-02-12 00:00:00

  • Reconstitution of active dimeric ribulose bisphosphate carboxylase from an unfoleded state depends on two chaperonin proteins and Mg-ATP.

    abstract::In vitro reconstitution of active ribulose bisphosphate carboxylase (Rubisco) from unfolded polypeptides is facilitated by the molecular chaperones: chaperonin-60 from Escherichia coli (groEL), yeast mitochondria (hsp60) or chloroplasts (Rubisco sub-unit-binding protein), together with chaperonin-10 from E. coli (groE...


    pub_type: 杂志文章


    authors: Goloubinoff P,Christeller JT,Gatenby AA,Lorimer GH

    更新日期:1989-12-21 00:00:00

  • Valuation of consumption and sale of forest goods from a Central American rain forest

    abstract::Researchers recognize that society needs accurate and comprehensive estimates of the economic value of rain forests to assess conservation and management options. Valuation of forests can help us to decide whether to implement policies that reconcile the value different groups attach to forests. Here we have measured ...


    pub_type: 杂志文章


    authors: Godoy R,Wilkie D,Overman H,Cubas A,Cubas G,Demmer J,McSweeney K,Brokaw N

    更新日期:2000-07-06 00:00:00

  • Demonstration by genetic suppression of interaction of GroE products with many proteins.

    abstract::The way in which proteins attain and maintain their final form is of fundamental importance. Recent work has focused on the role of a set of ubiquitous proteins, termed chaperonins, in the assembly of phage and multisubunit proteins. The range of chaperonin action is unknown; they could interact with most cellular pol...


    pub_type: 杂志文章


    authors: Van Dyk TK,Gatenby AA,LaRossa RA

    更新日期:1989-11-23 00:00:00

  • The role of interfacial lipids in stabilizing membrane protein oligomers.

    abstract::Oligomerization of membrane proteins in response to lipid binding has a critical role in many cell-signalling pathways but is often difficult to define or predict. Here we report the development of a mass spectrometry platform to determine simultaneously the presence of interfacial lipids and oligomeric stability and ...


    pub_type: 杂志文章


    authors: Gupta K,Donlan JAC,Hopper JTS,Uzdavinys P,Landreh M,Struwe WB,Drew D,Baldwin AJ,Stansfeld PJ,Robinson CV

    更新日期:2017-01-19 00:00:00

  • Field sports and conservation in the United Kingdom.

    abstract::Many natural habitats exist on privately owned land outside protected areas, but few governments can afford to enforce or subsidize conservation of this biodiversity. Even in some developed countries, conservation subsidy schemes have only achieved limited success. Fortunately, some landowners may be willing to accept...


    pub_type: 杂志文章


    authors: Oldfield TE,Smith RJ,Harrop SR,Leader-Williams N

    更新日期:2003-05-29 00:00:00

  • Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans.

    abstract::The nematode Caenorhabditis elegans is an important model for studying the genetics of ageing, with over 50 life-extension mutations known so far. However, little is known about the pathobiology of ageing in this species, limiting attempts to connect genotype with senescent phenotype. Using ultrastructural analysis an...


    pub_type: 杂志文章


    authors: Herndon LA,Schmeissner PJ,Dudaronek JM,Brown PA,Listner KM,Sakano Y,Paupard MC,Hall DH,Driscoll M

    更新日期:2002-10-24 00:00:00

  • Embryology of Early Jurassic dinosaur from China with evidence of preserved organic remains.

    abstract::Fossil dinosaur embryos are surprisingly rare, being almost entirely restricted to Upper Cretaceous strata that record the late stages of non-avian dinosaur evolution. Notable exceptions are the oldest known embryos from the Early Jurassic South African sauropodomorph Massospondylus and Late Jurassic embryos of a ther...


    pub_type: 杂志文章


    authors: Reisz RR,Huang TD,Roberts EM,Peng S,Sullivan C,Stein K,LeBlanc AR,Shieh D,Chang R,Chiang C,Yang C,Zhong S

    更新日期:2013-04-11 00:00:00