Abstract:
: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.
journal_name
Naturejournal_title
Natureauthors
Sun XJ,Rothenberg P,Kahn CR,Backer JM,Araki E,Wilden PA,Cahill DA,Goldstein BJ,White MFdoi
10.1038/352073a0keywords:
subject
Has Abstractpub_date
1991-07-04 00:00:00pages
73-7issue
6330eissn
0028-0836issn
1476-4687journal_volume
352pub_type
杂志文章相关文献
NATURE文献大全abstract::Injury causes a systemic inflammatory response syndrome (SIRS) that is clinically much like sepsis. Microbial pathogen-associated molecular patterns (PAMPs) activate innate immunocytes through pattern recognition receptors. Similarly, cellular injury can release endogenous 'damage'-associated molecular patterns (DAMPs...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature08780
更新日期:2010-03-04 00:00:00
abstract::More than 30 years ago, human beings looked back from the Moon to see the magnificent spectacle of Earth-rise. The technology that put us into space has since been used to assess the damage we are doing to our natural environment and is now being harnessed to monitor and predict diseases through space and time. Satell...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/415710a
更新日期:2002-02-07 00:00:00
abstract::Compartments in food webs are subgroups of taxa in which many strong interactions occur within the subgroups and few weak interactions occur between the subgroups. Theoretically, compartments increase the stability in networks, such as food webs. Compartments have been difficult to detect in empirical food webs becaus...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature02115
更新日期:2003-11-20 00:00:00
abstract::The promoter for a weakly expressed constitutive gene, the lactose repressor gene (lacI), has been sequenced, along with an 'up' promoter mutation Iq. The 10-fold enhancement in I expression found in Iq is the result of a single base change at position -35. To facilitate the sequencing, the lacI gene was cloned in a s...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/274762a0
更新日期:1978-08-24 00:00:00
abstract::The dehydration of subducting oceanic crust and upper mantle has been inferred both to promote the partial melting leading to arc magmatism and to induce intraslab intermediate-depth earthquakes, at depths of 50-300 km. Yet there is still no consensus about how slab hydration occurs or where and how much chemically bo...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01961
更新日期:2003-09-25 00:00:00
abstract::Body size is intrinsically linked to metabolic rate and life-history traits, and is a crucial determinant of food webs and community dynamics1,2. The increased temperatures associated with the urban-heat-island effect result in increased metabolic costs and are expected to drive shifts to smaller body sizes 3 . Urban ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-018-0140-0
更新日期:2018-06-01 00:00:00
abstract::The single endogenous DBA/2J ectropic provirus segregated concordantly with the dilute (d) coat colour mutation on chromosome 9 in 53/53 DBA/2J-derived recombinant inbred mouse strains and all seven inbred and mutant strains tested that carry the d allele. Analysis of DNA from a spontaneous DBA/2J d revertant (d+2J) s...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/293370a0
更新日期:1981-10-01 00:00:00
abstract::Extinction from habitat loss is the signature conservation problem of the twenty-first century. Despite its importance, estimating extinction rates is still highly uncertain because no proven direct methods or reliable data exist for verifying extinctions. The most widely used indirect method is to estimate extinction...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature09985
更新日期:2011-05-19 00:00:00
abstract::Uptake of glutamate into glial cells in the CNS maintains the extracellular glutamate concentration below neurotoxic levels and helps terminate its action as a neurotransmitter. The co-transport of two sodium ions on the glutamate carrier is thought to provide the energy needed to transport glutamate into cells. We ha...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/335433a0
更新日期:1988-09-29 00:00:00
abstract::Arbuscular mycorrhizal fungi (AMF) are ancient asexually reproducing organisms that form symbioses with the majority of plant species, improving plant nutrition and promoting plant diversity. Little is known about the evolution or organization of the genomes of any eukaryotic symbiont or ancient asexual organism. Dire...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature03069
更新日期:2005-01-13 00:00:00
abstract::The refined 1.9-A resolution structure of the periplasmic D-galactose-binding protein (GBP) reveals a calcium ion surrounded by seven ligands, all protein oxygen atoms. A nine-residue loop (amino-acid positions 134-142), which is preceded by a beta-turn and followed by a beta-strand, provides five ligands from every s...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/327635a0
更新日期:1987-06-18 00:00:00
abstract::The potential use of smallpox as a biological weapon has led to the production and stockpiling of smallpox vaccine and the immunization of some healthcare workers. Another public health goal is the licensing of a safer vaccine that could benefit the millions of people advised not to take the current one because they o...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature02331
更新日期:2004-03-11 00:00:00
abstract::Polar molecules have a rich internal structure and long-range dipole-dipole interactions, making them useful for quantum-controlled applications and fundamental investigations. Their potential fully unfolds at ultracold temperatures, where various effects are predicted in many-body physics, quantum information science...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11595
更新日期:2012-11-22 00:00:00
abstract::Caloric restriction extends lifespan in numerous species. In the budding yeast Saccharomyces cerevisiae this effect requires Sir2 (ref. 1), a member of the sirtuin family of NAD+-dependent deacetylases. Sirtuin activating compounds (STACs) can promote the survival of human cells and extend the replicative lifespan of ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature02789
更新日期:2004-08-05 00:00:00
abstract::Exoplanet detections have revolutionized astronomy, offering new insights into solar system architecture and planet demographics. While nearly 1,900 exoplanets have now been discovered and confirmed, none are still in the process of formation. Transition disks, protoplanetary disks with inner clearings best explained ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature15761
更新日期:2015-11-19 00:00:00
abstract::Where continental plates break apart, slip along multiple normal faults provides the required space for the Earth's crust to thin and subside. After initial rifting, however, the displacement on normal faults observed at the sea floor seems not to match the inferred extension. Here we show that crustal thinning can be...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04608
更新日期:2006-03-16 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 社论
doi:10.1038/d41586-018-07033-5
更新日期:2018-10-01 00:00:00
abstract::The recent discoveries of RNA interference and related RNA silencing pathways have revolutionized our understanding of gene regulation. RNA interference has been used as a research tool to control the expression of specific genes in numerous experimental organisms and has potential as a therapeutic strategy to reduce ...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/nature02872
更新日期:2004-09-16 00:00:00
abstract::For life to be sustained, mistakes in DNA repair must be tolerated when damage obscures the genetic information. In bacteria such as Escherichia coli, DNA damage elicits the well regulated 'SOS response'. For the extreme case of damage that cannot be repaired by conventional enzymes, there are proteins that allow the ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/380727a0
更新日期:1996-04-25 00:00:00
abstract::It has been established that many eukaryotic mRNAs contain poly(adenylic acid) tracts at their 3'-termini. The polyadenylation of mRNA occurs post-transcriptionally in the nucleus as a rapid, initial addition of 100-200 adenylate residues to the pre-mRNA (ref. 1). Subsequently, a slower chain extension (6-8 bases) of ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/267178a0
更新日期:1977-05-12 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 面试
doi:10.1038/d41586-018-07047-z
更新日期:2018-10-01 00:00:00
abstract::The direct involvement of the pituitary-adrenal axis in birth has been well established, at least in sheep, and its removal prolongs pregnancy. As part of the process the fetal sheep adrenal grows rapidly during the 10-15 d prepartum and is associated with a large rise in the plasma corticosteroid concentration. This ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/284616a0
更新日期:1980-04-17 00:00:00
abstract::Networks of interacting proteins orchestrate the responses of living cells to a variety of external stimuli, but how sensitive is the functioning of these protein networks to variations in their biochemical parameters? One possibility is that to achieve appropriate function, the reaction rate constants and enzyme conc...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/16483
更新日期:1999-01-14 00:00:00
abstract::The actions of many peptide growth factors include both stimulation and inhibition of cell proliferation, as well as effects unrelated to the control of cell growth. One peptide can have both stimulatory and inhibitory activity in a single cell, depending on the context of the other signal molecules present. ...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/332217a0
更新日期:1988-03-17 00:00:00
abstract::The intracellular free Ca2+ ([Ca2+]i) regulates the K+ conductance (GK) of the many types of cell membrane. The Ca2+ influx during an action potential activates this [Ca2+]i-linked GK in most neurones. In caffeine-treated sympathetic ganglion cells, however, Ca2+ released from an intracellular Ca2+ reservoir site anal...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/283204a0
更新日期:1980-01-10 00:00:00
abstract::The study of the extent and basis of gene-enzyme variation has long been a principal concern of population genetics. Numerous surveys have indicated considerable amounts of genetic variation detectable in natural populations, with few exceptions. The variances of average heterozygosities (H) between species and among ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/288580a0
更新日期:1980-12-11 00:00:00
abstract::The ventral tegmental area (VTA) and nucleus accumbens (NAc) are essential for learning about environmental stimuli associated with motivationally relevant outcomes. The task of signalling such events, both rewarding and aversive, from the VTA to the NAc has largely been ascribed to dopamine neurons. The VTA also cont...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11657
更新日期:2012-12-20 00:00:00
abstract::Nitrogen (N) limits the productivity of many ecosystems worldwide, thereby restricting the ability of terrestrial ecosystems to offset the effects of rising atmospheric CO(2) emissions naturally. Understanding input pathways of bioavailable N is therefore paramount for predicting carbon (C) storage on land, particular...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature10415
更新日期:2011-08-31 00:00:00
abstract::Jawless vertebrates use variable lymphocyte receptors (VLR) comprised of leucine-rich-repeat (LRR) segments as counterparts of the immunoglobulin-based receptors that jawed vertebrates use for antigen recognition. Highly diverse VLR genes are somatically assembled by the insertion of variable LRR sequences into incomp...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature08068
更新日期:2009-06-11 00:00:00
abstract::Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a compl...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13545
更新日期:2014-10-02 00:00:00