Abstract:
:Obesity and type 2 diabetes are characterized by insulin resistance. Mice lacking the protein-tyrosine phosphatase PTP1B in all tissues are hypersensitive to insulin but also have diminished fat stores. Because adiposity affects insulin sensitivity, the extent to which PTP1B directly regulates glucose homeostasis has been unclear. We report that mice lacking PTP1B only in muscle have body weight and adiposity comparable to those of controls on either chow or a high-fat diet (HFD). Muscle triglycerides and serum adipokines are also affected similarly by HFD in both groups. Nevertheless, muscle-specific PTP1B(-/-) mice exhibit increased muscle glucose uptake, improved systemic insulin sensitivity, and enhanced glucose tolerance. These findings correlate with and are most likely caused by increased phosphorylation of the insulin receptor and its downstream signaling components. Thus, muscle PTP1B plays a major role in regulating insulin action and glucose homeostasis, independent of adiposity. In addition, rosiglitazone treatment of HFD-fed control and muscle-specific PTP1B(-/-) mice revealed that rosiglitazone acts additively with PTP1B deletion. Therefore, combining PTP1B inhibition with thiazolidinediones should be more effective than either alone for treating insulin-resistant states.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Delibegovic M,Bence KK,Mody N,Hong EG,Ko HJ,Kim JK,Kahn BB,Neel BGdoi
10.1128/MCB.00959-07subject
Has Abstractpub_date
2007-11-01 00:00:00pages
7727-34issue
21eissn
0270-7306issn
1098-5549pii
MCB.00959-07journal_volume
27pub_type
杂志文章abstract::The extracellular signal-regulated kinase 1 and 2 (ERK1/2) mitogen-activated protein (MAP) kinase signaling pathway plays an important role in the proliferative response of mammalian cells to mitogens. However, the individual contribution of the isoforms ERK1 and ERK2 to cell proliferation control is unclear. The two ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00131-10
更新日期:2010-06-01 00:00:00
abstract::The GCM family of transcription factors consists of Drosophila melanogaster GCM, an important regulator of gliogenesis in the fly, and its two mammalian homologs, GCMa and GCMb. To clarify the function of these mammalian homologs, we deleted GCMa in mice. Genetic ablation of murine GCMa (mGCMa) is embryonic lethal, wi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.7.2466-2474.2000
更新日期:2000-04-01 00:00:00
abstract::SLP-76 is an adapter protein required for T-cell receptor (TCR) signaling. In particular, TCR-induced tyrosine phosphorylation and activation of phospholipase C-gamma1 (PLC-gamma1), and the resultant TCR-inducible gene expression, depend on SLP-76. Nonetheless, the mechanisms by which SLP-76 mediates PLC-gamma1 activa...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.13.4208-4218.2001
更新日期:2001-07-01 00:00:00
abstract::mRNA deadenylation is a key process in the regulation of translation and mRNA turnover. In Saccharomyces cerevisiae, deadenylation is primarily carried out by the Ccr4p and Caf1p/Pop2p subunits of the Ccr4-Not complex, which is conserved in eukaryotes including humans. Here we have identified an unconventional human C...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01483-06
更新日期:2007-03-01 00:00:00
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
doi:10.1128/MCB.24.22.9873-9886.2004
更新日期:2004-11-01 00:00:00
abstract::The simian virus 40 large T antigen (T antigen) inactivates tumor suppressor proteins and therefore has been used in numerous studies to probe the mechanisms that control cellular growth and to generate immortalized cell lines. Binding of T antigen to the Rb family of growth-regulatory proteins is necessary but not su...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.17.6233-6243.2000
更新日期:2000-09-01 00:00:00
abstract::The intracellular accumulation of the unspliced RNA of Rous sarcoma virus was decreased when translation was prematurely terminated by the introduction of nonsense codons within its 5' proximal gene, the gag gene. Subcellular fractionation of transfected cells suggested that nonsense codon-mediated instability occurre...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.3.1986
更新日期:1994-03-01 00:00:00
abstract::Csn3 (Cops3) maps to the mouse chromosome 11 region syntenic to the common deletion interval for the Smith-Magenis syndrome, a contiguous gene deletion syndrome. It encodes the third subunit of an eight-subunit protein complex, the COP9 signalosome (CSN), which controls a wide variety of molecules of different functio...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.19.6798-6808.2003
更新日期:2003-10-01 00:00:00
abstract::With v-yes DNA as the probe, a human cDNA library made from placental RNA was screened under relaxed conditions, and DNA clones derived from a novel genetic locus, termed lyn, were obtained. Nucleotide sequencing revealed that lyn could encode a novel tyrosine kinase that was very similar to mouse T-lymphocyte-specifi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.1.237
更新日期:1987-01-01 00:00:00
abstract::The 3' AU-rich region of human beta-1 interferon (hu-IFN beta) mRNA was found to act as a translational inhibitory element. The translational regulation of this 3' AU-rich sequence and the effect of its association with the poly(A) tail were studied in cell-free rabbit reticulocyte lysate. A poly(A)-rich hu-IFN beta m...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.6.3487
更新日期:1993-06-01 00:00:00
abstract::Gap junctions are membrane channels that permit the interchange of ions and other low-molecular-weight molecules between adjacent cells. Rous sarcoma virus (RSV)-induced transformation is marked by an early and profound disruption of gap-junctional communication, suggesting that these membrane structures may serve as ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.4.1754
更新日期:1990-04-01 00:00:00
abstract::Nutrients, drugs, and hormones influence transcription during differentiation and metabolism by binding to high-affinity nuclear receptors. In the absence of ligand, some but not all nuclear receptors repress transcription as a heterodimer with retinoid X receptor (RXR). Here we define a novel role for helix 12 (H12) ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.9.6448
更新日期:1999-09-01 00:00:00
abstract::Many selectable mutants of somatic Chinese hamster cells have been described, but very few of the mutations have been mapped to specific chromosomes. We have utilized the microcell-mediated gene transfer technique to establish the location of three selectable genetic markers on chromosome 2 of Chinese hamster. Microce...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.1.4.330
更新日期:1981-04-01 00:00:00
abstract::To investigate the role of insulin receptor substrate 1 (IRS-1) and IRS-2, the two ubiquitously expressed IRS proteins, in adipocyte differentiation, we established embryonic fibroblast cells with four different genotypes, i.e., wild-type, IRS-1 deficient (IRS-1(-/-)), IRS-2 deficient (IRS-2(-/-)), and IRS-1 IRS-2 dou...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.7.2521-2532.2001
更新日期:2001-04-01 00:00:00
abstract::The transcription factor NF-kappaB is overexpressed or constitutively activated in many cancer cells, where it induces expression of antiapoptotic genes correlating with resistance to anticancer therapies. Small molecules that inhibit the NF-kappaB signaling pathway could therefore be used to induce apoptosis in NF-ka...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.3.1061-1074.2003
更新日期:2003-02-01 00:00:00
abstract::USF is a family of basic helix-loop transcriptional factors that recognizes DNA-binding sites similar to those of the Myc oncoproteins. Here, various functional domains in the mouse USF2 protein were identified and characterized. Indirect immunofluorescence studies with transiently transfected cells revealed that both...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.4.1367
更新日期:1996-04-01 00:00:00
abstract::Although the primary function of U1 snRNA is to define the 5' donor site of an intron, it can also block the accumulation of a specific RNA transcript when it binds to a donor sequence within its terminal exon. This work was initiated to investigate if this property of U1 snRNA could be exploited as an effective metho...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.8.2815-2825.2001
更新日期:2001-04-01 00:00:00
abstract::The hemagglutinin-neuraminidase (HN) protein of paramyxoviruses is likely in the unusual class of glycoproteins with the amino terminus cytoplasmic and the carboxy terminus lumenal or external to the cell. The properties of the membrane insertion of the HN protein of Newcastle disease virus, a prototype paramyxovirus,...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.4.1386
更新日期:1987-04-01 00:00:00
abstract::Nitric oxide (NO) has been thought to regulate the immune system through S nitrosylation of the transcriptional factor NF-kappaB. However, regulatory effects of NO on innate immune responses are unclear. Here, we report that NO has a capability to control Toll-like receptor-mediated signaling through S nitrosylation. ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01412-07
更新日期:2008-02-01 00:00:00
abstract::Pseudo-exons are intronic sequences that are flanked by apparent consensus splice sites but that are not observed in spliced mRNAs. Pseudo-exons are often difficult to activate by mutation and have typically been viewed as a conceptual challenge to our understanding of how the spliceosome discriminates between authent...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.6.2237-2246.2006
更新日期:2006-03-01 00:00:00
abstract::With the murine retinoblastoma (RB) cDNA, a series of RB mutants were expressed in COS-1 cells and the pRB products were assessed for their ability (i) to bind to large T antigen (large T), (ii) to become modified by phosphorylation, and (iii) to localize in the nucleus. All point mutations and deletions introduced in...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.12.6586
更新日期:1990-12-01 00:00:00
abstract::Mammalian cells were observed to die under conditions in which nutrients were depleted and, simultaneously, macroautophagy was inhibited either genetically (by a small interfering RNA targeting Atg5, Atg6/Beclin 1-1, Atg10, or Atg12) or pharmacologically (by 3-methyladenine, hydroxychloroquine, bafilomycin A1, or mone...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.3.1025-1040.2005
更新日期:2005-02-01 00:00:00
abstract::The interleukin-2 (IL-2) receptor (IL-2R) consists of three distinct subunits (alpha, beta, and gamma c) and regulates proliferation of T lymphocytes. Intracellular signalling results from ligand-mediated heterodimerization of the cytoplasmic domains of the beta and gamma c chains. To identify the residues of gamma c ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.1.309
更新日期:1996-01-01 00:00:00
abstract::The uptake of various nucleosides by S49 mouse T-lymphoma cells and that by a single-step nucleoside transport-defective mutant thereof (AE1) were compared. Residual nucleoside entry into AE1 cells occurred via two routes, nonmediated permeation and saturable, non-concentrative transport with broad substrate specifici...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.1.160
更新日期:1987-01-01 00:00:00
abstract::In this study, we have constructed retroviral vectors expressing the interleukin-7 (IL-7) cDNA and have used infection with these retroviruses to express this cytokine endogenously in an IL-7-dependent pre-B-cell line. Infection with IL-7 retroviruses, but not with a control retrovirus, resulted in the conversion of t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.3.1590
更新日期:1991-03-01 00:00:00
abstract::Transcription by RNA polymerase I (pol I), pol II, and pol III requires the TATA-binding protein (TBP). This protein functions in association with distinct TBP-associated factors (TAFs) which may specify the nature of the polymerase selected for initiation at a promoter site. In the pol III transcription system, the T...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.12.7953
更新日期:1993-12-01 00:00:00
abstract::The human 4F2 cell surface antigen is a 120-kilodalton (kDa) disulfide-linked heterodimer which is composed of an 80- to 90-kDa glycosylated heavy chain (4F2HC) and a 35- to 40-kDa nonglycosylated light chain (4F2LC). 4F2 belongs to a family of inducible cell surface molecules which are involved in T-lymphocyte activa...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.9.3809
更新日期:1988-09-01 00:00:00
abstract::The male-specific-lethal (MSL) proteins in Drosophila melanogaster serve to adjust gene expression levels in male flies containing a single X chromosome to equal those in females with a double dose of X-linked genes. Together with noncoding roX RNA, MSL proteins form the "dosage compensation complex" (DCC), which inte...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.14.5947-5954.2005
更新日期:2005-07-01 00:00:00
abstract::Ure2p of Saccharomyces cerevisiae normally functions in blocking utilization of a poor nitrogen source when a good nitrogen source is available. The non-Mendelian genetic element [URE3] is a prion (infectious protein) form of Ure2p, so that overexpression of Ure2p induces the de novo appearance of infectious [URE3]. E...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.6.4516
更新日期:1999-06-01 00:00:00
abstract::The xCR1 protein is a maternal determinant and cofactor for nodal signaling in vertebrate embryos. The xCR1 protein accumulates specifically in the animal cells of Xenopus embryos, but maternal xCR1 mRNA is distributed equally throughout all embryonic cells. Here, we show that vegetal cell-specific translational repre...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01865-08
更新日期:2009-07-01 00:00:00