Insulin receptor substrates Irs1 and Irs2 coordinate skeletal muscle growth and metabolism via the Akt and AMPK pathways.


:Coordination of skeletal muscle growth and metabolism with nutrient availability is critical for metabolic homeostasis. To establish the role of insulin-like signaling in this process, we used muscle creatine kinase (MCK)-Cre to disrupt expression of insulin receptor substrates Irs1 and Irs2 in mouse skeletal/cardiac muscle. In 2-week-old mice, skeletal muscle masses and insulin responses were slightly affected by Irs1, but not Irs2, deficiency. In contrast, the combined deficiency of Irs1 and Irs2 (MDKO mice) severely reduced skeletal muscle growth and Akt→mTOR signaling and caused death by 3 weeks of age. Autopsy of MDKO mice revealed dilated cardiomyopathy, reflecting the known requirement of insulin-like signaling for cardiac function (P. G. Laustsen et al., Mol. Cell. Biol. 27:1649-1664, 2007). Impaired growth and function of MDKO skeletal muscle were accompanied by increased Foxo-dependent atrogene expression and amino acid release. MDKO mice were resistant to injected insulin, and their isolated skeletal muscles showed decreased insulin-stimulated glucose uptake. Glucose utilization in MDKO mice and isolated skeletal muscles was shifted from oxidation to lactate production, accompanied by an elevated AMP/ATP ratio that increased AMP-activated protein kinase (AMPK)→acetyl coenzyme A carboxylase (ACC) phosphorylation and fatty acid oxidation. Thus, insulin-like signaling via Irs1/2 is essential to terminate skeletal muscle catabolic/fasting pathways in the presence of adequate nutrition.


Mol Cell Biol


Long YC,Cheng Z,Copps KD,White MF




Has Abstract


2011-02-01 00:00:00














  • Interaction between PCNA and diubiquitinated Mcm10 is essential for cell growth in budding yeast.

    abstract::The minichromosome maintenance protein 10 (Mcm10) is an evolutionarily conserved factor that is essential for replication initiation and elongation. Mcm10 is part of the eukaryotic replication fork and interacts with a variety of proteins, including the Mcm2-7 helicase and DNA polymerase alpha/primase complexes. A mot...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Das-Bradoo S,Ricke RM,Bielinsky AK

    更新日期:2006-07-01 00:00:00

  • Detection of deletion mutations in pSV2gpt-transformed cells.

    abstract::We have developed a system to study mutations that affect xanthine-guanine phosphoribosyltransferase gene (gpt) expression in hypoxanthine-guanine phosphoribosyltransferase-deficient CHO cells that have been transformed by the plasmid vector pSV2gpt. One isolated transformant, designated AS52, carries a single copy of...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Tindall KR,Stankowski LF Jr,Machanoff R,Hsie AW

    更新日期:1984-07-01 00:00:00

  • Las1L is a nucleolar protein required for cell proliferation and ribosome biogenesis.

    abstract::Ribosome biogenesis is a highly regulated process ensuring that cell growth (increase in biomass) is coordinated with cell proliferation. The formation of eukaryotic ribosomes is a multistep process initiated by the transcription and processing of rRNA in the nucleolus. Concomitant with this, several preribosomal part...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Castle CD,Cassimere EK,Lee J,Denicourt C

    更新日期:2010-09-01 00:00:00

  • RB-dependent S-phase response to DNA damage.

    abstract::The retinoblastoma tumor suppressor protein (RB) is a potent inhibitor of cell proliferation. RB is expressed throughout the cell cycle, but its antiproliferative activity is neutralized by phosphorylation during the G(1)/S transition. RB plays an essential role in the G(1) arrest induced by a variety of growth inhibi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Knudsen KE,Booth D,Naderi S,Sever-Chroneos Z,Fribourg AF,Hunton IC,Feramisco JR,Wang JY,Knudsen ES

    更新日期:2000-10-01 00:00:00

  • Transcription alters chromosomal locations of cohesin in Saccharomyces cerevisiae.

    abstract::In eukaryotic cells, cohesion between sister chromatids allows chromosomes to biorient on the metaphase plate and holds them together until they separate into daughter cells during mitosis. Cohesion is mediated by the cohesin protein complex. Although the association of this complex with particular regions of the geno...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Bausch C,Noone S,Henry JM,Gaudenz K,Sanderson B,Seidel C,Gerton JL

    更新日期:2007-12-01 00:00:00

  • Role of Gab1 in UV-induced c-Jun NH2-terminal kinase activation and cell apoptosis.

    abstract::Exposure of mammalian cells to UV irradiation leads to activation of the c-Jun NH(2)-terminal protein kinase (JNK) pathway, which is associated with cell apoptosis. However, the molecular mechanism for JNK activation by UV exposure is not fully understood. We show here an essential role of a multisubstrate adapter, Ga...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Sun Y,Yuan J,Liu H,Shi Z,Baker K,Vuori K,Wu J,Feng GS

    更新日期:2004-02-01 00:00:00

  • Dynamic Methylation of an L1 Transduction Family during Reprogramming and Neurodifferentiation.

    abstract::The retrotransposon LINE-1 (L1) is a significant source of endogenous mutagenesis in humans. In each individual genome, a few retrotransposition-competent L1s (RC-L1s) can generate new heritable L1 insertions in the early embryo, primordial germ line, and germ cells. L1 retrotransposition can also occur in the neurona...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Salvador-Palomeque C,Sanchez-Luque FJ,Fortuna PRJ,Ewing AD,Wolvetang EJ,Richardson SR,Faulkner GJ

    更新日期:2019-03-19 00:00:00

  • Functional role of laminin carbohydrate.

    abstract::Previous work showed that tunicamycin suppresses glycosylation of laminin. In the present work, the role of glycosylation in the secretion of laminin and in the disulfide bonding of laminin subunits was studied, using tunicamycin to inhibit glycosylation. Tunicamycin inhibited extensively the secretion of laminin into...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Howe CC

    更新日期:1984-01-01 00:00:00

  • Transcription mediated by NFAT is highly inducible in effector CD4+ T helper 2 (Th2) cells but not in Th1 cells.

    abstract::Transcriptional factors of the NFAT family play an important role in regulating the expression of several cytokine genes during the immune response, such as the genes for interleukin 2 (IL-2) and IL-4, among others. Upon antigen stimulation, precursor CD4+ T helper (pTh) cells proliferate and differentiate into two po...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Rincón M,Flavell RA

    更新日期:1997-03-01 00:00:00

  • The product of HUM1, a novel yeast gene, is required for vacuolar Ca2+/H+ exchange and is related to mammalian Na+/Ca2+ exchangers.

    abstract::Calcineurin, or PP2B, plays a critical role in mediating Ca2+-dependent signaling in many cell types. In yeast cells, this highly conserved protein phosphatase regulates aspects of ion homeostasis and cell wall synthesis. We show that calcineurin mutants are sensitive to high concentrations of Mn2+ and identify two ge...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Pozos TC,Sekler I,Cyert MS

    更新日期:1996-07-01 00:00:00

  • Recognition DNA sequences of interferon regulatory factor 1 (IRF-1) and IRF-2, regulators of cell growth and the interferon system.

    abstract::Interferon (IFN) regulatory factor 1 (IRF-1) and IRF-2 were originally identified as transcription factors involved in the regulation of the IFN system. IRF-1 functions as a transcriptional activator, while IRF-2 represses IRF-1 function. More recently, evidence has been provided that IRF-1 and IRF-2 manifest antionco...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Tanaka N,Kawakami T,Taniguchi T

    更新日期:1993-08-01 00:00:00

  • U1A inhibits cleavage at the immunoglobulin M heavy-chain secretory poly(A) site by binding between the two downstream GU-rich regions.

    abstract::The immunoglobulin M heavy-chain locus contains two poly(A) sites which are alternatively expressed during B-cell differentiation. Despite its promoter proximal location, the secretory poly(A) site is not expressed in undifferentiated cells. Crucial to the activation of the secretory poly(A) site during B-cell differe...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Phillips C,Pachikara N,Gunderson SI

    更新日期:2004-07-01 00:00:00

  • DHTKD1 Deficiency Causes Charcot-Marie-Tooth Disease in Mice.

    abstract::DHTKD1, a part of 2-ketoadipic acid dehydrogenase complex, is involved in lysine and tryptophan catabolism. Mutations in DHTKD1 block the metabolic pathway and cause 2-aminoadipic and 2-oxoadipic aciduria (AMOXAD), an autosomal recessive inborn metabolic disorder. In addition, a nonsense mutation in DHTKD1 that we ide...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Xu WY,Zhu H,Shen Y,Wan YH,Tu XD,Wu WT,Tang L,Zhang HX,Lu SY,Jin XL,Fei J,Wang ZG

    更新日期:2018-06-14 00:00:00

  • Involvement of Brca1 in S-phase and G(2)-phase checkpoints after ionizing irradiation.

    abstract::Cell cycle arrests in the G(1), S, and G(2) phases occur in mammalian cells after ionizing irradiation and appear to protect cells from permanent genetic damage and transformation. Though Brca1 clearly participates in cellular responses to ionizing radiation (IR), conflicting conclusions have been drawn about whether ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Xu B,Kim St,Kastan MB

    更新日期:2001-05-01 00:00:00

  • Enhancer-dependent transcriptional oscillations in mouse erythroleukemia cells.

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Feng YQ,Alami R,Bouhassira EE

    更新日期:1999-07-01 00:00:00

  • Extracellular signal-regulated kinase signaling regulates the opposing roles of JUN family transcription factors at ETS/AP-1 sites and in cell migration.

    abstract::JUN transcription factors bind DNA as part of the AP-1 complex, regulate many cellular processes, and play a key role in oncogenesis. The three JUN proteins (c-JUN, JUNB, and JUND) can have both redundant and unique functions depending on the biological phenotype and cell type assayed. Mechanisms that allow this dynam...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Selvaraj N,Budka JA,Ferris MW,Plotnik JP,Hollenhorst PC

    更新日期:2015-01-01 00:00:00

  • Topoisomerase-specific drug sensitivity in relation to cell cycle progression.

    abstract::The nuclear enzyme DNA topoisomerase II catalyzes the breakage and resealing of duplex DNA and plays an important role in several genetic processes. It also mediates the DNA cleavage activity and cytotoxicity of clinically important anticancer agents such as etoposide. We have examined the activity of topoisomerase II...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Chow KC,Ross WE

    更新日期:1987-09-01 00:00:00

  • Cells lacking Rieske iron-sulfur protein have a reactive oxygen species-associated decrease in respiratory complexes I and IV.

    abstract::Mitochondrial respiratory complexes of the electron transport chain (CI, CIII, and CIV) can be assembled into larger structures forming supercomplexes. We analyzed the assembly/stability of respiratory complexes in mouse lung fibroblasts lacking the Rieske iron-sulfur protein (RISP knockout [KO]cells), one of the cata...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Diaz F,Enríquez JA,Moraes CT

    更新日期:2012-01-01 00:00:00

  • Novel functional dissection of the localization-specific roles of budding yeast polo kinase Cdc5p.

    abstract::Budding yeast polo kinase Cdc5p localizes to the spindle pole body (SPB) and to the bud-neck and plays multiple roles during M-phase progression. To dissect localization-specific mitotic functions of Cdc5p, we tethered a localization-defective N-terminal kinase domain of Cdc5p (Cdc5pDeltaC) to the SPB or to the bud-ne...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Park JE,Park CJ,Sakchaisri K,Karpova T,Asano S,McNally J,Sunwoo Y,Leem SH,Lee KS

    更新日期:2004-11-01 00:00:00

  • DNA-binding properties of the Drosophila melanogaster zeste gene product.

    abstract::The ability of the zeste moiety of beta-galactosidase-zeste fusion proteins synthesized in Escherichia coli to bind specific DNA sequences was examined. Such fusion proteins recognize a region of the white locus upstream of the start of transcription; this region has previously been shown to be required for genetic in...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Mansukhani A,Crickmore A,Sherwood PW,Goldberg ML

    更新日期:1988-02-01 00:00:00

  • Hepatitis C virus nonstructural 5B protein regulates tumor necrosis factor alpha signaling through effects on cellular IkappaB kinase.

    abstract::Hepatitis C virus (HCV) NS5B protein is a membrane-associated phosphoprotein that possesses an RNA-dependent RNA polymerase activity. We recently reported that NS5A protein interacts with TRAF2 and modulates tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB and Jun N-terminal protein kinase (JNK). Since NS5A a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Choi SH,Park KJ,Ahn BY,Jung G,Lai MM,Hwang SB

    更新日期:2006-04-01 00:00:00

  • Isolation and transcriptional characterization of three genes which function at start, the controlling event of the Saccharomyces cerevisiae cell division cycle: CDC36, CDC37, and CDC39.

    abstract::The genes CDC36, CDC37, and CDC39, thought to function in the cell division control process in Saccharomyces cerevisiae, were isolated from a recombinant plasmid library prepared by partial digestion of S. cerevisiae genomic DNA with Sau3A and insertion into the S. cerevisiae-Escherichia coli shuttle vector YRp7. In e...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Breter HJ,Ferguson J,Peterson TA,Reed SI

    更新日期:1983-05-01 00:00:00

  • Expression of a cDNA sequence encoding human purine nucleoside phosphorylase in rodent and human cells.

    abstract::A cDNA sequence which contains the entire coding region for human purine nucleoside phosphorylase (PNP) was recombined for selection and expression in mammalian cells. Plasmids containing either the simian virus 40 early promoter or the mouse metallothionein promoter positioned just upstream of the PNP coding sequence...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: McIvor RS,Goddard JM,Simonsen CC,Martin DW Jr

    更新日期:1985-06-01 00:00:00

  • The tumor suppressor p53 and histone deacetylase 1 are antagonistic regulators of the cyclin-dependent kinase inhibitor p21/WAF1/CIP1 gene.

    abstract::The cyclin-dependent kinase inhibitor p21/WAF1/CIP1 is an important regulator of cell cycle progression, senescence, and differentiation. Genotoxic stress leads to activation of the tumor suppressor p53 and subsequently to induction of p21 expression. Here we show that the tumor suppressor p53 cooperates with the tran...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Lagger G,Doetzlhofer A,Schuettengruber B,Haidweger E,Simboeck E,Tischler J,Chiocca S,Suske G,Rotheneder H,Wintersberger E,Seiser C

    更新日期:2003-04-01 00:00:00

  • Complex recognition site for the group I intron-encoded endonuclease I-SceII.

    abstract::We have characterized features of the site recognized by a double-stranded DNA endonuclease, I-SceII, encoded by intron 4 alpha of the yeast mitochondrial COX1 gene. We determined the effects of 36 point mutations on the cleavage efficiency of natural and synthetic substrates containing the Saccharomyces capensis I-Sc...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Wernette C,Saldanha R,Smith D,Ming D,Perlman PS,Butow RA

    更新日期:1992-02-01 00:00:00

  • The human SETMAR protein preserves most of the activities of the ancestral Hsmar1 transposase.

    abstract::Transposons have contributed protein coding sequences to a unexpectedly large number of human genes. Except for the V(D)J recombinase and telomerase, all remain of unknown function. Here we investigate the activity of the human SETMAR protein, a highly expressed fusion between a histone H3 methylase and a mariner fami...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Liu D,Bischerour J,Siddique A,Buisine N,Bigot Y,Chalmers R

    更新日期:2007-02-01 00:00:00

  • DEAD Box 1 Facilitates Removal of RNA and Homologous Recombination at DNA Double-Strand Breaks.

    abstract::Although RNA and RNA-binding proteins have been linked to double-strand breaks (DSBs), little is known regarding their roles in the cellular response to DSBs and, if any, in the repair process. Here, we provide direct evidence for the presence of RNA-DNA hybrids at DSBs and suggest that binding of RNA to DNA at DSBs m...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Li L,Germain DR,Poon HY,Hildebrandt MR,Monckton EA,McDonald D,Hendzel MJ,Godbout R

    更新日期:2016-10-28 00:00:00

  • A proline-rich sequence unique to MEK1 and MEK2 is required for raf binding and regulates MEK function.

    abstract::Mammalian MEK1 and MEK2 contain a proline-rich (PR) sequence that is absent both from the yeast homologs Ste7 and Byr1 and from a recently cloned activator of the JNK/stress-activated protein kinases, SEK1/MKK4. Since this PR sequence occurs in MEKs that are regulated by Raf family enzymes but is missing from MEKs and...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Catling AD,Schaeffer HJ,Reuter CW,Reddy GR,Weber MJ

    更新日期:1995-10-01 00:00:00

  • T-antigen-DNA polymerase alpha complex implicated in simian virus 40 DNA replication.

    abstract::We have combined in vitro DNA replication reactions and immunological techniques to analyze biochemical interactions between simian virus (SV40) large T antigen and components of the cellular replication apparatus. First, in vitro SV40 DNA replication was characterized with specific origin mutants. Next, monoclonal an...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Smale ST,Tjian R

    更新日期:1986-11-01 00:00:00

  • Positive and negative modulation of Jun action by thyroid hormone receptor at a unique AP1 site.

    abstract::We have characterized the putative AP1 site in the backbone of pUC plasmids and found unique regulatory effects. The site, which mapped to a 19-bp region around nucleotide 37, conferred transcriptional activation by Jun or Jun/Fos that was boosted up to fivefold by unliganded thyroid hormone receptor (TR). Thyroid hor...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Lopez G,Schaufele F,Webb P,Holloway JM,Baxter JD,Kushner PJ

    更新日期:1993-05-01 00:00:00