Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism.


:The broad expression of the insulin receptor suggests that the spectrum of insulin function has not been fully described. A cell type expressing this receptor is the osteoblast, a bone-specific cell favoring glucose metabolism through a hormone, osteocalcin, that becomes active once uncarboxylated. We show here that insulin signaling in osteoblasts is necessary for whole-body glucose homeostasis because it increases osteocalcin activity. To achieve this function insulin signaling in osteoblasts takes advantage of the regulation of osteoclastic bone resorption exerted by osteoblasts. Indeed, since bone resorption occurs at a pH acidic enough to decarboxylate proteins, osteoclasts determine the carboxylation status and function of osteocalcin. Accordingly, increasing or decreasing insulin signaling in osteoblasts promotes or hampers glucose metabolism in a bone resorption-dependent manner in mice and humans. Hence, in a feed-forward loop, insulin signals in osteoblasts activate a hormone, osteocalcin, that promotes glucose metabolism.






Ferron M,Wei J,Yoshizawa T,Del Fattore A,DePinho RA,Teti A,Ducy P,Karsenty G




Has Abstract


2010-07-23 00:00:00
















  • Polo delivers a PICH to the kinetochore.

    abstract::In this issue, Baumann et al. (2007) identify a helicase PICH that localizes to "threads" that remain connected between sister kinetochores after they have separated in anaphase. These threads are thought to be catenated centromeric DNA. PICH contributes to the mitotic checkpoint by recruiting Mad2 to kinetochores and...


    pub_type: 评论,杂志文章


    authors: Yen TJ

    更新日期:2007-01-12 00:00:00

  • The Implication of Early Chromatin Changes in X Chromosome Inactivation.

    abstract::During development, the precise relationships between transcription and chromatin modifications often remain unclear. We use the X chromosome inactivation (XCI) paradigm to explore the implication of chromatin changes in gene silencing. Using female mouse embryonic stem cells, we initiate XCI by inducing Xist and then...


    pub_type: 杂志文章


    authors: Żylicz JJ,Bousard A,Žumer K,Dossin F,Mohammad E,da Rocha ST,Schwalb B,Syx L,Dingli F,Loew D,Cramer P,Heard E

    更新日期:2019-01-10 00:00:00

  • Promoter-selective activation domains in Oct-1 and Oct-2 direct differential activation of an snRNA and mRNA promoter.

    abstract::The promoter specificity of transcriptional activators is generally thought to be conferred by the specificity of the DNA-binding domain, which brings the activation domain to the appropriate promoter sequence. We show here, however, that Oct-1 and Oct-2 can differentially activate transcription not through DNA bindin...


    pub_type: 杂志文章


    authors: Tanaka M,Lai JS,Herr W

    更新日期:1992-02-21 00:00:00

  • Genetic isolation of ADA2: a potential transcriptional adaptor required for function of certain acidic activation domains.

    abstract::We have devised a genetic strategy to isolate the target of acidic activation domains of transcriptional activators based on toxicity in yeast cells of the chimeric activator, GAL4-VP16. Toxicity required the integrity of both the VP16 acidic activation domain and the GAL4 DNA-binding domain, suggesting that inhibitio...


    pub_type: 杂志文章


    authors: Berger SL,Piña B,Silverman N,Marcus GA,Agapite J,Regier JL,Triezenberg SJ,Guarente L

    更新日期:1992-07-24 00:00:00

  • The bacterial toxin RelE displays codon-specific cleavage of mRNAs in the ribosomal A site.

    abstract::The Escherichia coli relBE operon encodes a toxin-antitoxin pair, RelE-RelB. RelB can reverse inhibition of protein synthesis by RelE in vivo. We have found that although RelE does not degrade free RNA, it cleaves mRNA in the ribosomal A site with high codon specificity. Among stop codons UAG is cleaved with fast, UAA...


    pub_type: 杂志文章


    authors: Pedersen K,Zavialov AV,Pavlov MY,Elf J,Gerdes K,Ehrenberg M

    更新日期:2003-01-10 00:00:00

  • Isolation and characterization of T antigen-negative revertants from a line of transformed rat cells containing one copy of the SV40 genome.

    abstract::Negative selection with FUdR produced revertants from the transformed rat line 14B, which contains one insertion of the SV40 viral genome (Botchan, Topp and Sambrook, 1976). 14B contains nuclear T antigen, grows to a high density, grows in low serum and is anchorage-independent. The revertants fall into three classes ...


    pub_type: 杂志文章


    authors: Steinberg B,Pollack R,Topp W,Botchan M

    更新日期:1978-01-01 00:00:00

  • A neural circuit mechanism integrating motivational state with memory expression in Drosophila.

    abstract::Behavioral expression of food-associated memory in fruit flies is constrained by satiety and promoted by hunger, suggesting an influence of motivational state. Here, we identify a neural mechanism that integrates the internal state of hunger and appetitive memory. We show that stimulation of neurons that express neuro...


    pub_type: 杂志文章


    authors: Krashes MJ,DasGupta S,Vreede A,White B,Armstrong JD,Waddell S

    更新日期:2009-10-16 00:00:00

  • The kinky propulsion of Spiroplasma.

    abstract::Bacteria have evolved many different means of generating movement. In this issue of Cell, Shaevitz et al. (2005) describe the swimming movement of a helical bacterium called Spiroplasma. They discover that Spiroplasma propels itself by generating two temporally distinct kinks that travel the length of the bacterium. T...


    pub_type: 评论,杂志文章,评审


    authors: Wolgemuth CW,Charon NW

    更新日期:2005-09-23 00:00:00

  • The pro region of BPTI facilitates folding.

    abstract::The in vitro folding pathway of bovine pancreatic trypsin inhibitor (BPTI) has been described previously in terms of the disulfide-bonded intermediates that accumulate during folding of the protein. Folding is slow, occurring in hours at pH 7.3, 25 degrees C. In addition, approximately half of the BPTI molecules becom...


    pub_type: 杂志文章


    authors: Weissman JS,Kim PS

    更新日期:1992-11-27 00:00:00

  • Mechanisms of TGF-beta signaling from cell membrane to the nucleus.

    abstract::TGF-beta signaling controls a plethora of cellular responses and figures prominently in animal development. Recent cellular, biochemical, and structural studies have revealed significant insight into the mechanisms of the activation of TGF-beta receptors through ligand binding, the activation of Smad proteins through ...


    pub_type: 杂志文章,评审


    authors: Shi Y,Massagué J

    更新日期:2003-06-13 00:00:00

  • A novel divalent cation-binding site in the A domain of the beta 2 integrin CR3 (CD11b/CD18) is essential for ligand binding.

    abstract::A recombinant peptide encoding the CD11b A domain bound 54Mn2+ with a high affinity. Other divalent cations, including Mg2+, Zn2+, Ni2+, Co2+, and Cd2+, but not Ca2+ or Ba2+, competed effectively for Mn2+ binding. Amino acid substitutions within two conserved and noncontiguous regions in the recombinant peptide abolis...


    pub_type: 杂志文章


    authors: Michishita M,Videm V,Arnaout MA

    更新日期:1993-03-26 00:00:00

  • Poly(A) polymerase and a dissociable polyadenylation stimulatory factor encoded by vaccinia virus.

    abstract::mRNA made in eukaryotic cells typically has a 3' poly(A) tail that is added posttranscriptionally. To investigate mechanisms by which 3' poly(A) is formed, we identified the genes for the two vaccina virus-encoded polypeptides, VP55 and VP39. Primer-dependent polyadenylation activity was associated exclusively with pu...


    pub_type: 杂志文章


    authors: Gershon PD,Ahn BY,Garfield M,Moss B

    更新日期:1991-09-20 00:00:00

  • Lung Cancer: A Wily Genetic Opponent.

    abstract::In two companion reports, the TRACERx consortium investigates tumor heterogeneity and evolution in early-stage non-small cell lung cancer. The studies highlight the prognostic value of copy-number heterogeneity assessment in tumor biopsies and circulating tumor DNA detection in plasma and suggest that tracking the evo...


    pub_type: 评论,杂志文章


    authors: Hsu PP,Shaw AT

    更新日期:2017-05-18 00:00:00

  • Global mapping of the topography and magnitude of proteolytic events in apoptosis.

    abstract::Proteolysis is a key regulatory process that promotes the (in)activation, translocation, and/or degradation of proteins. As such, there is considerable interest in methods to comprehensively characterize proteolytic pathways in biological systems. Here, we describe a robust and versatile proteomic platform that enable...


    pub_type: 杂志文章


    authors: Dix MM,Simon GM,Cravatt BF

    更新日期:2008-08-22 00:00:00

  • Location of sequences on the adenovirus genome coding for the 5.5S RNA.

    abstract::The origin of a low molecular weight virus-associated RNA (VA-RNA) was mapped by hybridization of VA-RNA to specific fragments of adenovirus type 2 DNA, obtained after cleavage with three different restriction endonucleases. VA-RNA was found to hybridize exculsively to the l-strand [strand with low buoyant density in ...


    pub_type: 杂志文章


    authors: Pettersson U,Philipson L

    更新日期:1975-09-01 00:00:00

  • Transposons in place of telomeric repeats at a Drosophila telomere.

    abstract::We present the first isolation of the terminal DNA of an intact Drosophila telomere. It differs from those isolated from other eukaryotes by the lack of short tandem repeats at the terminus. The terminal 14.5 kb is composed of four tandem elements derived from two families of non-long terminal repeat retrotransposons ...


    pub_type: 杂志文章


    authors: Levis RW,Ganesan R,Houtchens K,Tolar LA,Sheen FM

    更新日期:1993-12-17 00:00:00

  • Lipid-Sorting Specificity Encoded in K-Ras Membrane Anchor Regulates Signal Output.

    abstract::K-Ras is targeted to the plasma membrane by a C-terminal membrane anchor that comprises a farnesyl-cysteine-methyl-ester and a polybasic domain. We used quantitative spatial imaging and atomistic molecular dynamics simulations to examine molecular details of K-Ras plasma membrane binding. We found that the K-Ras ancho...


    pub_type: 杂志文章


    authors: Zhou Y,Prakash P,Liang H,Cho KJ,Gorfe AA,Hancock JF

    更新日期:2017-01-12 00:00:00

  • A symmetrical six-base-pair target site sequence determines Tn10 insertion specificity.

    abstract::Transposon Tn10 inserts at many sites in the bacterial chromosome, but preferentially inserts at particular hotspots. We believe we have identified the target DNA signal responsible for this specificity. We have determined the DNA sequences of 11 Tn10 insertion sites and identified a particular 6 base pair (bp) symmet...


    pub_type: 杂志文章


    authors: Halling SM,Kleckner N

    更新日期:1982-01-01 00:00:00

  • The Interfaces of Genetic Conflict Are Hot Spots for Innovation.

    abstract::RNA-guided Cas9 endonucleases protect bacteria from viral infection and have been creatively repurposed as programmable molecular scalpels for surgical manipulation of DNA. Now, two papers in Cell (Pawluk et al. and Rauch et al.) identify viral proteins that suppress Cas9 and may function like molecular sheaths for th...


    pub_type: 评论,杂志文章


    authors: Carter J,Hoffman C,Wiedenheft B

    更新日期:2017-01-12 00:00:00

  • Rethinking differentiation: stem cells, regeneration, and plasticity.

    abstract::Cell differentiation is an essential process for the development, growth, reproduction, and longevity of all multicellular organisms, and its regulation has been the focus of intense investigation for the past four decades. The study of natural and induced stem cells has ushered an age of re-examination of what it mea...


    pub_type: 杂志文章,评审


    authors: Sánchez Alvarado A,Yamanaka S

    更新日期:2014-03-27 00:00:00

  • FtsK Is a DNA motor protein that activates chromosome dimer resolution by switching the catalytic state of the XerC and XerD recombinases.

    abstract::FtsK acts at the bacterial division septum to couple chromosome segregation with cell division. We demonstrate that a truncated FtsK derivative, FtsK(50C), uses ATP hydrolysis to translocate along duplex DNA as a multimer in vitro, consistent with FtsK having an in vivo role in pumping DNA through the closing division...


    pub_type: 杂志文章


    authors: Aussel L,Barre FX,Aroyo M,Stasiak A,Stasiak AZ,Sherratt D

    更新日期:2002-01-25 00:00:00

  • Localization of specificity determining sites in cadherin cell adhesion molecules.

    abstract::Cadherins are a group of homophilic intercellular adhesion molecules; each member of this family exhibits binding specificity. Here, we attempted to map the sites for the specificities of these molecules by analyzing adhesives selectivities of the cells that express chimeric and point-mutated E- and P-cadherin. The re...


    pub_type: 杂志文章


    authors: Nose A,Tsuji K,Takeichi M

    更新日期:1990-04-06 00:00:00

  • Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.

    abstract::We performed a comprehensive assessment of rare inherited variation in autism spectrum disorder (ASD) by analyzing whole-genome sequences of 2,308 individuals from families with multiple affected children. We implicate 69 genes in ASD risk, including 24 passing genome-wide Bonferroni correction and 16 new ASD risk gen...


    pub_type: 杂志文章


    authors: Ruzzo EK,Pérez-Cano L,Jung JY,Wang LK,Kashef-Haghighi D,Hartl C,Singh C,Xu J,Hoekstra JN,Leventhal O,Leppä VM,Gandal MJ,Paskov K,Stockham N,Polioudakis D,Lowe JK,Prober DA,Geschwind DH,Wall DP

    更新日期:2019-08-08 00:00:00

  • Organoid models of human and mouse ductal pancreatic cancer.

    abstract::Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tiss...


    pub_type: 杂志文章


    authors: Boj SF,Hwang CI,Baker LA,Chio II,Engle DD,Corbo V,Jager M,Ponz-Sarvise M,Tiriac H,Spector MS,Gracanin A,Oni T,Yu KH,van Boxtel R,Huch M,Rivera KD,Wilson JP,Feigin ME,Öhlund D,Handly-Santana A,Ardito-Abraham CM,L

    更新日期:2015-01-15 00:00:00

  • A putative Ras GTPase activating protein acts as a negative regulator of signaling by the Sevenless receptor tyrosine kinase.

    abstract::A Drosophila gene with similarity to the mammalian Ras GTPase activating protein has been isolated in screens for mutations that affect eye development. Inactivation of the locus, Gap1, mimics constitutive activation of the Sevenless receptor tyrosine kinase and eliminates the need for a functional Sevenless protein i...


    pub_type: 杂志文章


    authors: Gaul U,Mardon G,Rubin GM

    更新日期:1992-03-20 00:00:00

  • Identification of human Rap1: implications for telomere evolution.

    abstract::It has been puzzling that mammalian telomeric proteins, including TRF1, TRF2, tankyrase, and TIN2 have no recognized orthologs in budding yeast. Here, we describe a human protein, hRap1, that is an ortholog of the yeast telomeric protein, scRap1p. hRap1 has three conserved sequence motifs in common with scRap1, is loc...


    pub_type: 杂志文章


    authors: Li B,Oestreich S,de Lange T

    更新日期:2000-05-26 00:00:00

  • Mutant PTEN in Cancer: Worse Than Nothing.

    abstract::Tumor suppressors block the development of cancer and are often lost during tumor development. Papa et al. show that partial loss of normal PTEN tumor suppressor function can be compounded by additional disruption caused by the expression of inactive mutant PTEN protein. This has significant implications for patients ...


    pub_type: 评论,杂志文章


    authors: Leslie NR,den Hertog J

    更新日期:2014-04-24 00:00:00

  • The DHR78 nuclear receptor is required for ecdysteroid signaling during the onset of Drosophila metamorphosis.

    abstract::Pulses of ecdysteroids direct Drosophila through its life cycle by activating stage- and tissue-specific genetic regulatory hierarchies. Here we show that an orphan nuclear receptor, DHR78, functions at the top of the ecdysteroid regulatory hierarchies. Null mutations in DHR78 lead to lethality during the third larval...


    pub_type: 杂志文章


    authors: Fisk GJ,Thummel CS

    更新日期:1998-05-15 00:00:00

  • The discovery of statins.

    abstract::This year, the Lasker Foundation confers its Clinical Medical Research Award on Akira Endo for his isolation from fungi of statins, potent inhibitors of cholesterol synthesis in the liver. The introduction of statins to clinical practice has markedly reduced morbidity and mortality from atherosclerotic cardiovascular ...


    pub_type: 历史文章,杂志文章


    authors: Stossel TP

    更新日期:2008-09-19 00:00:00

  • Mini-P1 plasmid replication: the autoregulation-sequestration paradox.

    abstract::It has been proposed that the initiator protein RepA is rate limiting for mini-P1 plasmid replication, and that the role of the plasmid copy number control locus is to sequester the initiator and thus reduce replication. This proposal appears inconsistent with the observation that RepA is autoregulated, since the prot...


    pub_type: 杂志文章


    authors: Chattoraj DK,Mason RJ,Wickner SH

    更新日期:1988-02-26 00:00:00