Abstract:
:Both systemic insulin resistance and tissue-specific insulin resistance have been described in Drosophila and are accompanied by many indicators of metabolic disease. The downstream mediators of insulin-resistant pathophysiology remain unclear. We analyzed insulin signaling in the fat body studying loss and gain of function. When expression of the sole Drosophila insulin receptor (InR) was reduced in larval fat bodies, animals exhibited developmental delay and reduced size in a diet-dependent manner. Fat body InR knockdown also led to reduced survival on high-sugar diets. To look downstream of InR at potential mediators of insulin resistance, transcriptome sequencing (RNA-seq) studies in insulin-resistant fat bodies revealed differential expression of genes, including those involved in innate immunity. Obesity-associated insulin resistance led to increased susceptibility of flies to infection, as in humans. Reduced innate immunity was dependent on fat body InR expression. The peptidoglycan recognition proteins (PGRPs) PGRP-SB2 and PGRP-SC2 were selected for further study based on differential expression studies. Downregulating PGRP-SB2 selectively in the fat body protected animals from the deleterious effects of overnutrition, whereas downregulating PGRP-SC2 produced InR-like phenotypes. These studies extend earlier work linking the immune and insulin signaling pathways and identify new targets of insulin signaling that could serve as potential drug targets to treat type 2 diabetes.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Musselman LP,Fink JL,Grant AR,Gatto JA,Tuthill BF 2nd,Baranski TJdoi
10.1128/MCB.00259-17subject
Has Abstractpub_date
2017-12-29 00:00:00issue
2eissn
0270-7306issn
1098-5549pii
MCB.00259-17journal_volume
38pub_type
杂志文章abstract::The CBP/p300 family of proteins comprises related acetyltransferases that coactivate signal-responsive transcription. Recent evidence suggests that p300/CBP may also interact directly with complexes that mediate different aspects of DNA metabolism such as replication and repair. In this report, we show that loss of dC...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01283-06
更新日期:2007-01-01 00:00:00
abstract::The death-associated protein (DAP) kinase family includes three protein kinases, DAP kinase, DAP kinase-related protein 1, and ZIP kinase, which display 80% amino acid identity within their catalytic domains and are functionally linked to common subcellular changes occurring during cell death, such as the process of m...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.19.8611-8626.2004
更新日期:2004-10-01 00:00:00
abstract::Nuclear microinjection of c-H-ras DNA induced DNA synthesis in reversibly nonproliferating quiescent human cells. The proto-oncogene and oncogene forms were equally effective inducers. In contrast, c-H-ras DNA either alone or in combination with the adenovirus E1A gene did not cause terminally nondividing senescent ce...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.8.2990
更新日期:1986-08-01 00:00:00
abstract::Following chromosome duplication in S phase of the cell cycle, the sister chromatids are linked by cohesin. At the onset of anaphase, separase cleaves cohesin and thereby initiates sister chromatid separation. Separase activation results from the destruction of its inhibitor, securin, which is triggered by a ubiquitin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00235-08
更新日期:2008-09-01 00:00:00
abstract::The Suppressor of the Hairy wing [Su(Hw)] binding region within the gypsy retrotransposon is the best known chromatin insulator in Drosophila melanogaster. According to previous data, two copies of the gypsy insulator inserted between an enhancer and a promoter neutralize each other's actions, which is indicative of a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.21.9283-9291.2005
更新日期:2005-11-01 00:00:00
abstract::The folate receptor type alpha (FR-alpha) is a promising tumor marker and target. Here, we investigate the mechanistic basis for the tumor specificity and vast overexpression of FR-alpha. Among representative FR-alpha-positive (HeLa and JAR) and FR-alpha-negative (MG63, Caki1, and HT3) cell lines, the transcription ra...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.6.2202-2212.2003
更新日期:2003-03-01 00:00:00
abstract::The slow/cardiac troponin C (cTnC) gene is expressed in three distinct striated muscle lineages: cardiac myocytes, embryonic fast skeletal myotubes, and adult slow skeletal myocytes. We have reported previously that cTnC gene expression in cardiac muscle is regulated by a cardiac-specific promoter/enhancer located in ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.3.1870
更新日期:1994-03-01 00:00:00
abstract::XPC is responsible for DNA damage sensing in nucleotide excision repair (NER). Mutations in XPC lead to a defect in NER and to xeroderma pigmentosum (XP-C). Here, we analyzed the biochemical properties behind mutations found within three patients: one amino acid substitution (P334H, XP1MI, and GM02096), one amino acid...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00781-08
更新日期:2008-12-01 00:00:00
abstract::The Rel family of transcription factors participate in a diverse array of processes, including acute responses to injury and infection, lymphocyte differentiation, and embryonic patterning. These proteins show homology in an extended region spanning about 300 amino acids (the Rel homology domain [RHD]). The RHD mediat...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.7.3627
更新日期:1995-07-01 00:00:00
abstract::We report the isolation and molecular characterization of the mouse grb2 gene. The product of this gene, the Grb2 protein, is highly related to the Caenorhabditis elegans sem-5 gene product and the human GRB2 protein and displays the same SH3-SH2-SH3 structural motifs. In situ hybridization studies revealed that the m...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.9.5500
更新日期:1993-09-01 00:00:00
abstract::Sporulation in Saccharomyces cerevisiae normally occurs only in MATa/MAT alpha diploids. We show that mutations in RME1 bypassed the requirements for both a and alpha mating type information in sporulation and therefore allowed MATa/MATa and MAT alpha/MAT alpha diploids to sporulate. RME1 was located on chromosome VII...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.1.10.958
更新日期:1981-10-01 00:00:00
abstract::We have previously proposed that IQGAP1, an effector of Rac1 and Cdc42, negatively regulates cadherin-mediated cell-cell adhesion by interacting with beta-catenin and by causing the dissociation of alpha-catenin from cadherin-beta-catenin-alpha-catenin complexes and that activated Rac1 and Cdc42 positively regulate ca...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.6.2165-2183.2001
更新日期:2001-03-01 00:00:00
abstract::In order to determine whether partial methylation of the herpes simplex virus (HSV) tk gene prevents tk gene expression, the HSV tk gene was cloned as single-stranded DNA. By in vitro second-strand DNA synthesis, specific HSV tk gene segments were methylated, and the hemimethylated DNA molecules were microinjected int...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.3.2004
更新日期:1994-03-01 00:00:00
abstract::G proteins are molecular switches that control a wide variety of physiological functions, including neurotransmission, transcriptional activation, cell migration, cell growth. and proliferation. The ability of GTPases to participate in signaling events is determined by the ratio of GTP-bound to GDP-bound forms in the ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.7.2476-2488.2003
更新日期:2003-04-01 00:00:00
abstract::Neighboring genes encoding the mouse sex-limited protein (Slp) and fourth component of complement (C4) show extensive homology. In contrast to C4, however, Slp is regulated by androgen. One region of the Slp gene capable of hormonal response following transfection was located about 2 kilobases upstream of the transcri...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.6.2350
更新日期:1988-06-01 00:00:00
abstract::GCN4 is a transcriptional activator of amino acid-biosynthetic genes in the yeast Saccharomyces cerevisiae. GCN2, a translational activator of GCN4 expression, contains a domain homologous to the catalytic subunit of eucaryotic protein kinases. Substitution of a highly conserved lysine residue in the kinase domain abo...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.6.2820
更新日期:1990-06-01 00:00:00
abstract::The female-sterile ovarian tumor gene, otu, is located in cytological region 7F1 on the Drosophila melanogaster chromosome map. We have mapped the gene at the molecular level by using four dysgenic alleles and two revertant derivatives of these alleles as well as an ethyl methanesulfonate-induced allele. The insertion...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.4.1481
更新日期:1988-04-01 00:00:00
abstract::An extracellular acid phosphatase was detected in the growth media of Leishmania donovani promastigotes. The enzyme was released at all stages of the growth cycle and in amounts which accounted for 90% of the total amount of this enzyme in the culture. The exoenzyme exhibited a pH optimum of 4.5 to 5.0 and was active ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.2.1.76
更新日期:1982-01-01 00:00:00
abstract::Mutations in the Saccharomyces cerevisiae alpha-factor receptor that lead to improved response to Saccharomyces kluyveri alpha-factor were identified and sequenced. Mutants were isolated from cells bearing randomly mutagenized receptor gene (STE2) plasmids by an in vivo screen. Five mutations lead to substitutions in ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.9.3959
更新日期:1992-09-01 00:00:00
abstract::The GLN3 gene of Saccharomyces cerevisiae is required for the activation of transcription of a number of genes in response to the replacement of glutamine by glutamate as source of nitrogen. We cloned the GLN3 gene and constructed null alleles by gene disruption. GLN3 is not essential for growth, but increased copies ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.12.6216
更新日期:1991-12-01 00:00:00
abstract::Prdm1/Blimp-1 is a master regulator of gene expression in diverse tissues of the developing embryo and adult organism. Its C-terminal zinc finger domain mediates nuclear import, DNA binding, and recruitment of the corepressors G9a and HDAC1/2. Alternatively spliced transcripts lacking exon 7 sequences encode a structu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00174-12
更新日期:2012-09-01 00:00:00
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
doi:10.1128/mcb.6.11.4077
更新日期:1986-11-01 00:00:00
abstract::A novel protein, p55CDC, has been identified in cycling mammalian cells. This transcript is readily detectable in all exponentially growing cell lines but disappears when cells are chemically induced to fall out of the cell cycle and differentiate. The p55CDC protein appears to be essential for cell division, since tr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.5.3350
更新日期:1994-05-01 00:00:00
abstract::Two alleles of the Drosophila melanogaster Rfc4 (DmRfc4) gene, which encodes subunit 4 of the replication factor C (RFC) complex, cause striking defects in mitotic chromosome cohesion and condensation. These mutations produce larval phenotypes consistent with a role in DNA replication but also result in mitotic chromo...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.15.5156-5168.2001
更新日期:2001-08-01 00:00:00
abstract::Spatial control of cytokinesis is essential for proper cell division. The molecular mechanisms that anchor the dynamic assembly and constriction of the cytokinetic ring at the plasma membrane remain unclear. In the fission yeast Schizosaccharomyces pombe, the cytokinetic ring is assembled in the cell middle from corti...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01286-12
更新日期:2013-01-01 00:00:00
abstract::It is well established that steroid receptor function requires interaction with coactivators. However, the mechanisms through which steroid receptors elicit precise assembly of coactivator complexes and the way the steroid activation signal is transduced remain elusive. Using a T47D cell line stably integrated with a ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.11.3763-3773.2003
更新日期:2003-06-01 00:00:00
abstract::We have determined the complete nucleotide sequences of two chicken beta-tubulin genes, beta 1 and beta 2. These genes display an unusual pattern of segmental homology which indicates that they originally arose by gene duplication and have subsequently coevolved by a process that included localized gene conversion or ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.9.2454
更新日期:1985-09-01 00:00:00
abstract::We previously purified and characterized functionally the Escherichia coli-expressed product of the human subgroup C adenovirus E1A 13S mRNA (B. Ferguson, N. Jones, J. Richter, and M. Rosenberg, Science 224:1343-1346, 1984; B. Krippl, B. Ferguson, M. Rosenberg, and H. Westphal, Proc. Natl. Acad. Sci. USA 81:6988-6992,...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.10.2653
更新日期:1985-10-01 00:00:00
abstract::Using an expression cDNA cloning approach, we examined human tumor cell lines for novel oncogenes that might evade detection by conventional techniques. We isolated a transforming sequence that was highly efficient in transforming NIH 3T3 mouse fibroblasts. DNA sequence analysis identified the gene as the human homolo...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.2.762
更新日期:1993-02-01 00:00:00
abstract::The cardiac troponin C (cTnC) gene produces identical transcripts in slow-twitch skeletal muscle and in heart muscle (R. Gahlmann, R. Wade, P. Gunning, and L. Kedes, J. Mol. Biol. 201:379-391, 1988). A separate gene encodes the fast-twitch skeletal muscle troponin C and is not expressed in heart muscle. We have used t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.11.6752
更新日期:1993-11-01 00:00:00