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














  • Simulation of Hubbard model physics in WSe2/WS2 moiré superlattices.

    abstract::The Hubbard model, formulated by physicist John Hubbard in the 1960s1, is a simple theoretical model of interacting quantum particles in a lattice. The model is thought to capture the essential physics of high-temperature superconductors, magnetic insulators and other complex quantum many-body ground states2,3. Althou...


    pub_type: 杂志文章


    authors: Tang Y,Li L,Li T,Xu Y,Liu S,Barmak K,Watanabe K,Taniguchi T,MacDonald AH,Shan J,Mak KF

    更新日期:2020-03-01 00:00:00

  • 1970s and 'Patient 0' HIV-1 genomes illuminate early HIV/AIDS history in North America.

    abstract::The emergence of HIV-1 group M subtype B in North American men who have sex with men was a key turning point in the HIV/AIDS pandemic. Phylogenetic studies have suggested cryptic subtype B circulation in the United States (US) throughout the 1970s and an even older presence in the Caribbean. However, these temporal an...


    pub_type: 历史文章,杂志文章


    authors: Worobey M,Watts TD,McKay RA,Suchard MA,Granade T,Teuwen DE,Koblin BA,Heneine W,Lemey P,Jaffe HW

    更新日期:2016-11-03 00:00:00

  • Regulated degradation of a class V myosin receptor directs movement of the yeast vacuole.

    abstract::Normal cellular function requires that organelles be positioned in specific locations. The direction in which molecular motors move organelles is based in part on the polarity of microtubules and actin filaments. However, this alone does not determine the intracellular destination of organelles. For example, the yeast...


    pub_type: 杂志文章


    authors: Tang F,Kauffman EJ,Novak JL,Nau JJ,Catlett NL,Weisman LS

    更新日期:2003-03-06 00:00:00

  • Blazar spectral variability as explained by a twisted inhomogeneous jet.

    abstract::Blazars are active galactic nuclei, which are powerful sources of radiation whose central engine is located in the core of the host galaxy. Blazar emission is dominated by non-thermal radiation from a jet that moves relativistically towards us, and therefore undergoes Doppler beaming. This beaming causes flux enhancem...


    pub_type: 杂志文章


    authors: Raiteri CM,Villata M,Acosta-Pulido JA,Agudo I,Arkharov AA,Bachev R,Baida GV,Benítez E,Borman GA,Boschin W,Bozhilov V,Butuzova MS,Calcidese P,Carnerero MI,Carosati D,Casadio C,Castro-Segura N,Chen WP,Damljanovic G,D'

    更新日期:2017-12-21 00:00:00

  • Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6.

    abstract::Wild-type p53 protein has many properties consistent with its being the product of a tumour suppressor gene. Although the normal roles of tumour suppressor genes are still largely unknown, it seems that they could be involved in promoting cell differentiation as well as in mediating growth arrest by growth-inhibitory ...


    pub_type: 杂志文章


    authors: Yonish-Rouach E,Resnitzky D,Lotem J,Sachs L,Kimchi A,Oren M

    更新日期:1991-07-25 00:00:00

  • A single amino acid of the cholecystokinin-B/gastrin receptor determines specificity for non-peptide antagonists.

    abstract::The brain cholecystokinin-B/gastrin receptor (CCK-B/gastrin) has been implicated in mediating anxiety, panic attacks, satiety, and the perception of pain. The canine and human CCK-B/gastrin receptors share 90% amino-acid identity and have similar agonist affinities. These receptors can be selectively blocked by the no...


    pub_type: 杂志文章


    authors: Beinborn M,Lee YM,McBride EW,Quinn SM,Kopin AS

    更新日期:1993-03-25 00:00:00

  • Molecular characterization of Ph1 as a major chromosome pairing locus in polyploid wheat.

    abstract::The foundation of western civilization owes much to the high fertility of bread wheat, which results from the stability of its polyploid genome. Despite possessing multiple sets of related chromosomes, hexaploid (bread) and tetraploid (pasta) wheat both behave as diploids at meiosis. Correct pairing of homologous chro...


    pub_type: 杂志文章


    authors: Griffiths S,Sharp R,Foote TN,Bertin I,Wanous M,Reader S,Colas I,Moore G

    更新日期:2006-02-09 00:00:00

  • Thalamic control of sensory selection in divided attention.

    abstract::How the brain selects appropriate sensory inputs and suppresses distractors is unknown. Given the well-established role of the prefrontal cortex (PFC) in executive function, its interactions with sensory cortical areas during attention have been hypothesized to control sensory selection. To test this idea and, more ge...


    pub_type: 杂志文章


    authors: Wimmer RD,Schmitt LI,Davidson TJ,Nakajima M,Deisseroth K,Halassa MM

    更新日期:2015-10-29 00:00:00

  • Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome.

    abstract::In eukaryotes, accurate chromosome segregation in mitosis and meiosis maintains genome stability and prevents aneuploidy. Kinetochores are large protein complexes that, by assembling onto specialized Cenp-A nucleosomes1,2, function to connect centromeric chromatin to microtubules of the mitotic spindle3,4. Whereas the...


    pub_type: 杂志文章


    authors: Yan K,Yang J,Zhang Z,McLaughlin SH,Chang L,Fasci D,Ehrenhofer-Murray AE,Heck AJR,Barford D

    更新日期:2019-10-01 00:00:00

  • Cortical area MT and the perception of stereoscopic depth.

    abstract::Stereopsis is the perception of depth based on small positional differences between images formed on the two retinae (known as binocular disparity). Neurons that respond selectively to binocular disparity were first described three decades ago, and have since been observed in many visual areas of the primate brain, in...


    pub_type: 杂志文章


    authors: DeAngelis GC,Cumming BG,Newsome WT

    更新日期:1998-08-13 00:00:00

  • Defective T-cell receptor signalling and positive selection of Vav-deficient CD4+ CD8+ thymocytes.

    abstract::During lymphocyte development, cellular proliferation and positive and negative selection events ensure the production of T and B lymphocytes bearing highly diverse, but self-tolerant, repertoires of antigen receptors. These processes are initiated when engagement of growth-factor receptors, or the T and B lymphocyte ...


    pub_type: 杂志文章


    authors: Fischer KD,Zmuldzinas A,Gardner S,Barbacid M,Bernstein A,Guidos C

    更新日期:1995-03-30 00:00:00

  • A sphingosine-1-phosphate receptor regulates cell migration during vertebrate heart development.

    abstract::Coordinated cell migration is essential in many fundamental biological processes including embryonic development, organogenesis, wound healing and the immune response. During organogenesis, groups of cells are directed to specific locations within the embryo. Here we show that the zebrafish miles apart (mil) mutation ...


    pub_type: 杂志文章


    authors: Kupperman E,An S,Osborne N,Waldron S,Stainier DY

    更新日期:2000-07-13 00:00:00

  • Dynamics of nucleosome remodelling by individual ACF complexes.

    abstract::The ATP-dependent chromatin assembly and remodelling factor (ACF) functions to generate regularly spaced nucleosomes, which are required for heritable gene silencing. The mechanism by which ACF mobilizes nucleosomes remains poorly understood. Here we report a single-molecule FRET study that monitors the remodelling of...


    pub_type: 杂志文章


    authors: Blosser TR,Yang JG,Stone MD,Narlikar GJ,Zhuang X

    更新日期:2009-12-24 00:00:00

  • HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses.

    abstract::The activation of innate immune responses by nucleic acids is crucial to protective and pathological immunities and is mediated by the transmembrane Toll-like receptors (TLRs) and cytosolic receptors. However, it remains unknown whether a mechanism exists that integrates these nucleic-acid-sensing systems. Here we sho...


    pub_type: 杂志文章


    authors: Yanai H,Ban T,Wang Z,Choi MK,Kawamura T,Negishi H,Nakasato M,Lu Y,Hangai S,Koshiba R,Savitsky D,Ronfani L,Akira S,Bianchi ME,Honda K,Tamura T,Kodama T,Taniguchi T

    更新日期:2009-11-05 00:00:00

  • Interplay of electron-lattice interactions and superconductivity in superconductivity in Bi2Sr2CaCu2O8+delta.

    abstract::Formation of electron pairs is essential to superconductivity. For conventional superconductors, tunnelling spectroscopy has established that pairing is mediated by bosonic modes (phonons); a peak in the second derivative of tunnel current d2I/dV2 corresponds to each phonon mode. For high-transition-temperature (high-...


    pub_type: 杂志文章


    authors: Lee J,Fujita K,McElroy K,Slezak JA,Wang M,Aiura Y,Bando H,Ishikado M,Masui T,Zhu JX,Balatsky AV,Eisaki H,Uchida S,Davis JC

    更新日期:2006-08-03 00:00:00

  • Isolation of rare circulating tumour cells in cancer patients by microchip technology.

    abstract::Viable tumour-derived epithelial cells (circulating tumour cells or CTCs) have been identified in peripheral blood from cancer patients and are probably the origin of intractable metastatic disease. Although extremely rare, CTCs represent a potential alternative to invasive biopsies as a source of tumour tissue for th...


    pub_type: 杂志文章


    authors: Nagrath S,Sequist LV,Maheswaran S,Bell DW,Irimia D,Ulkus L,Smith MR,Kwak EL,Digumarthy S,Muzikansky A,Ryan P,Balis UJ,Tompkins RG,Haber DA,Toner M

    更新日期:2007-12-20 00:00:00

  • Biomechanics: rubber bands reduce the cost of carrying loads.

    abstract::Vertical movement of the hip during locomotion causes a loaded backpack to be accelerated with each step, which imposes large peak forces on the wearer. Here we show that using bungee cords to suspend the load from a backpack frame reduces not only its vertical movement, and hence its vertical force on the carrier, bu...


    pub_type: 杂志文章


    authors: Rome LC,Flynn L,Yoo TD

    更新日期:2006-12-21 00:00:00

  • Effect of recombinant soluble CD4 in rhesus monkeys infected with simian immunodeficiency virus of macaques.

    abstract::The CD4 molecule is a high-affinity cell-surface receptor for the human immunodeficiency virus (HIV-1) and a soluble truncated form of CD4 produced by recombinant DNA technology is a potent inhibitor of HIV-1 replication and HIV-1-induced cell fusion in vitro. Rhesus monkeys infected with the simian immunodeficiency v...


    pub_type: 杂志文章


    authors: Watanabe M,Reimann KA,DeLong PA,Liu T,Fisher RA,Letvin NL

    更新日期:1989-01-19 00:00:00

  • Light-dependent phosphorylation of rhodopsin by beta-adrenergic receptor kinase.

    abstract::The structural components involved in transduction of extracellular signals as diverse as a photon of light impinging on the retina or a hormone molecule impinging on a cell have been highly conserved. These components include a recognition unit or receptor (for example, the beta-adrenergic receptor (beta AR) for cate...


    pub_type: 杂志文章


    authors: Benovic JL,Mayor F Jr,Somers RL,Caron MG,Lefkowitz RJ

    更新日期:1986-06-26 00:00:00

  • Domain interactions of H-2 class I antigens alter cytotoxic T-cell recognition sites.

    abstract::H-2 class I antigens appear to direct the recognition of virus-infected and neoplastic transformed cells by cytotoxic T lymphocytes (CTLs). Here, to identify the regions of class I antigens involved in CTL recognition, four hybrid class I genes were constructed in which exons were exchanged between the H-2Kb and H-2Db...


    pub_type: 杂志文章


    authors: Allen H,Wraith D,Pala P,Askonas B,Flavell RA

    更新日期:1984-05-17 00:00:00

  • Greenland ice-sheet contribution to sea-level rise buffered by meltwater storage in firn.

    abstract::Surface melt on the Greenland ice sheet has shown increasing trends in areal extent and duration since the beginning of the satellite era. Records for melt were broken in 2005, 2007, 2010 and 2012. Much of the increased surface melt is occurring in the percolation zone, a region of the accumulation area that is perenn...


    pub_type: 杂志文章


    authors: Harper J,Humphrey N,Pfeffer WT,Brown J,Fettweis X

    更新日期:2012-11-08 00:00:00

  • Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys.

    abstract::A recombinant adenovirus serotype 5 (rAd5) vector-based vaccine for HIV-1 has recently failed in a phase 2b efficacy study in humans. Consistent with these results, preclinical studies have demonstrated that rAd5 vectors expressing simian immunodeficiency virus (SIV) Gag failed to reduce peak or setpoint viral loads a...


    pub_type: 杂志文章


    authors: Liu J,O'Brien KL,Lynch DM,Simmons NL,La Porte A,Riggs AM,Abbink P,Coffey RT,Grandpre LE,Seaman MS,Landucci G,Forthal DN,Montefiori DC,Carville A,Mansfield KG,Havenga MJ,Pau MG,Goudsmit J,Barouch DH

    更新日期:2009-01-01 00:00:00

  • The 'Higgs' amplitude mode at the two-dimensional superfluid/Mott insulator transition.

    abstract::Spontaneous symmetry breaking plays a key role in our understanding of nature. In relativistic quantum field theory, a broken continuous symmetry leads to the emergence of two types of fundamental excitation: massless Nambu-Goldstone modes and a massive 'Higgs' amplitude mode. An excitation of Higgs type is of crucial...


    pub_type: 杂志文章


    authors: Endres M,Fukuhara T,Pekker D,Cheneau M,Schauss P,Gross C,Demler E,Kuhr S,Bloch I

    更新日期:2012-07-25 00:00:00

  • Homologous expressed genes in the human sex chromosome pairing region.

    abstract::The human sex chromosomes share a pair of homologous genes which independently encode a cell-surface antigen defined by the monoclonal antibody 12E7 (refs 1, 2; see refs 3, 4 for review). The X-located homologue, MIC2X, escapes X-inactivation and the equivalent Y-located locus, MIC2Y, was one of the first genes shown ...


    pub_type: 杂志文章


    authors: Buckle V,Mondello C,Darling S,Craig IW,Goodfellow PN

    更新日期:1985-10-24 00:00:00

  • Blood flow changes in human somatosensory cortex during anticipated stimulation.

    abstract::Positron emission tomography (PET) measurements of brain blood flow were used to monitor changes in the human primary and secondary somatosensory cortices during the period when somatosensory stimuli were expected. In anticipation of either focal or innocuous touching, or localized, painful shocks, blood flow decrease...


    pub_type: 杂志文章


    authors: Drevets WC,Burton H,Videen TO,Snyder AZ,Simpson JR Jr,Raichle ME

    更新日期:1995-01-19 00:00:00

  • Isolation of a gene regulated by hydrostatic pressure in a deep-sea bacterium.

    abstract::Barophilic bacteria inhabit the deep oceans, and the specific functional modifications and regulatory mechanisms which govern adaptation to hydrostatic pressure are beginning to be understood. For example, the rate of production of several proteins by some hydrothermal vent archaebacteria and the degree of saturation ...


    pub_type: 杂志文章


    authors: Bartlett D,Wright M,Yayanos AA,Silverman M

    更新日期:1989-11-30 00:00:00

  • A point mutation in the A gamma-globin gene promoter in Greek hereditary persistence of fetal haemoglobin.

    abstract::Hereditary persistance of fetal haemoglobin (HPFH) is a benign condition characterized by the production in adulthood of more than 1% fetal haemoglobin (HbF, alpha 2 gamma 2) in the absence of erythropoietic stress. Several genetic types have been discerned based on the level of HbF produced, the relative contribution...


    pub_type: 杂志文章


    authors: Collins FS,Metherall JE,Yamakawa M,Pan J,Weissman SM,Forget BG

    更新日期:1985-01-24 00:00:00

  • Reversible shape change of Triton-treated erythrocyte ghosts induced by Ca2+ and Mg-ATP.

    abstract::The shape of the human erythrocyte depends on intracellular ATP content and echinocytic erythrocyte ghosts obtained in the presence of Mg-ATP acquire a diskocytic shape after incubation at 37 degrees C; however, agreement is lacking about the molecular basis of the shape changes. The suggestion that phosphorylation of...


    pub_type: 杂志文章


    authors: Jinbu Y,Sato S,Nakao M

    更新日期:1984-01-26 00:00:00

  • Genome-wide analysis identifies NR4A1 as a key mediator of T cell dysfunction.

    abstract::T cells become dysfunctional when they encounter self antigens or are exposed to chronic infection or to the tumour microenvironment1. The function of T cells is tightly regulated by a combinational co-stimulatory signal, and dominance of negative co-stimulation results in T cell dysfunction2. However, the molecular m...


    pub_type: 杂志文章


    authors: Liu X,Wang Y,Lu H,Li J,Yan X,Xiao M,Hao J,Alekseev A,Khong H,Chen T,Huang R,Wu J,Zhao Q,Wu Q,Xu S,Wang X,Jin W,Yu S,Wang Y,Wei L,Wang A,Zhong B,Ni L,Liu X,Nurieva R,Ye L,Tian Q,Bian XW,Dong C

    更新日期:2019-03-01 00:00:00

  • S-phase feedback control in budding yeast independent of tyrosine phosphorylation of p34cdc28.

    abstract::In somatic cells, entry into mitosis depends on the completion of DNA synthesis. This dependency is established by S-phase feedback controls that arrest cell division when damaged or unreplicated DNA is present. In the fission yeast Schizosaccharomyces pombe, mutations that interfere with the phosphorylation of tyrosi...


    pub_type: 杂志文章


    authors: Sorger PK,Murray AW

    更新日期:1992-01-23 00:00:00