Abstract:
:Phosphatidylinositol (PI) 3-kinase plays an important role in various metabolic actions of insulin including glucose uptake and glycogen synthesis. Although PI 3-kinase primarily functions as a lipid kinase which preferentially phosphorylates the D-3 position of phospholipids, the effect of hydrolysis of the key PI 3-kinase product PI 3,4,5-triphosphate [PI(3,4,5)P3] on these biological responses is unknown. We recently cloned rat SH2-containing inositol phosphatase 2 (SHIP2) cDNA which possesses the 5'-phosphatase activity to hydrolyze PI(3,4,5)P3 to PI 3,4-bisphosphate [PI(3,4)P2] and which is mainly expressed in the target tissues of insulin. To study the role of SHIP2 in insulin signaling, wild-type SHIP2 (WT-SHIP2) and 5'-phosphatase-defective SHIP2 (Delta IP-SHIP2) were overexpressed in 3T3-L1 adipocytes by means of adenovirus-mediated gene transfer. Early events of insulin signaling including insulin-induced tyrosine phosphorylation of the insulin receptor beta subunit and IRS-1, IRS-1 association with the p85 subunit, and PI 3-kinase activity were not affected by expression of either WT-SHIP2 or Delta IP-SHIP2. Because WT-SHIP2 possesses the 5'-phosphatase catalytic region, its overexpression marked by decreased insulin-induced PI(3,4,5)P3 production, as expected. In contrast, the amount of PI(3,4,5)P3 was increased by the expression of Delta IP-SHIP2, indicating that Delta IP-SHIP2 functions in a dominant-negative manner in 3T3-L1 adipocytes. Both PI(3,4,5)P3 and PI(3,4)P2 were known to possibly activate downstream targets Akt and protein kinase C lambda in vitro. Importantly, expression of WT-SHIP2 inhibited insulin-induced activation of Akt and protein kinase C lambda, whereas these activations were increased by expression of Delta IP-SHIP2 in vivo. Consistent with the regulation of downstream molecules of PI 3-kinase, insulin-induced 2-deoxyglucose uptake and Glut4 translocation were decreased by expression of WT-SHIP2 and increased by expression of Delta IP-SHIP2. In addition, insulin-induced phosphorylation of GSK-3beta and activation of PP1 followed by activation of glycogen synthase and glycogen synthesis were decreased by expression of WT-SHIP2 and increased by the expression of Delta IP-SHIP2. These results indicate that SHIP2 negatively regulates metabolic signaling of insulin via the 5'-phosphatase activity and that PI(3,4,5)P3 rather than PI(3,4)P2 is important for in vivo regulation of insulin-induced activation of downstream molecules of PI 3-kinase leading to glucose uptake and glycogen synthesis.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Wada T,Sasaoka T,Funaki M,Hori H,Murakami S,Ishiki M,Haruta T,Asano T,Ogawa W,Ishihara H,Kobayashi Mdoi
10.1128/MCB.21.5.1633-1646.2001subject
Has Abstractpub_date
2001-03-01 00:00:00pages
1633-46issue
5eissn
0270-7306issn
1098-5549journal_volume
21pub_type
杂志文章abstract::Glucocorticoid-induced leucine zipper (GILZ) is a leucine zipper protein, whose expression is augmented by dexamethasone (DEX) treatment and downregulated by T-cell receptor (TCR) triggering. Stable expression of GILZ in T cells mimics some of the effects of glucocorticoid hormones (GCH) in GCH-mediated immunosuppress...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.22.7929-7941.2002
更新日期:2002-11-01 00:00:00
abstract::Kinase-negative mutants of S49 mouse lymphoma cells, which lack detectable catalytic (C) subunit of cyclic AMP-dependent protein kinase, nevertheless contain cytoplasmic mRNAs for the two major forms of C subunit, C alpha and C beta. Investigation of the metabolism of C subunits in wild-type and mutant cells was under...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.2.705
更新日期:1991-02-01 00:00:00
abstract::A 215-base-pair (bp) region of the mouse MOPC 41 kappa light-chain immunoglobulin gene enhancer has been analyzed for specific binding of lymphoid and nonlymphoid nuclear factors. Mobility shift assays with a series of overlapping DNA fragments have mapped DNA-binding sites for three unique factors. The B-cell-specifi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.10.4239
更新日期:1989-10-01 00:00:00
abstract::Alkylpurine-DNA-N-glycosylase (APNG) null mice have been generated by homologous recombination in embryonic stem cells. The null status of the animals was confirmed at the mRNA level by reverse transcription-PCR and by the inability of cell extracts of tissues from the knockout (ko) animals to release 3-methyladenine ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.10.5828
更新日期:1998-10-01 00:00:00
abstract::NMYC is a gene whose amplification and overexpression have been implicated in the generation of certain human malignancies. Little is known of how the expression of NMYC is normally controlled. We have therefore characterized transcription from the gene and the structure and stability of the resulting mRNAs. Transcrip...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.12.4266
更新日期:1987-12-01 00:00:00
abstract::Sortilin is a member of the Vps10p domain family of neuropeptide and neurotrophin binding neuronal receptors. The family members interact with and partly share a variety of ligands and partake in intracellular sorting and protein transport as well as in transmembrane signal transduction. Thus, sortilin mediates the tr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00274-10
更新日期:2010-09-01 00:00:00
abstract::The use of mutant mice plays a pivotal role in determining the function of genes, and the recently reported germ line transposition of the Sleeping Beauty (SB) transposon would provide a novel system to facilitate this approach. In this study, we characterized SB transposition in the mouse germ line and assessed its p...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.24.9189-9207.2003
更新日期:2003-12-01 00:00:00
abstract::The Wnt-1 proto-oncogene is essential for proper development of the midbrain and is expressed in a spatially and temporally restricted manner during central nervous system development in mice. In vitro, the gene is specifically transcribed during the retinoic acid (RA)-induced neuroectodermal differentiation of the P1...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.3.1590
更新日期:1993-03-01 00:00:00
abstract::A significant challenge to our understanding of eukaryotic transcriptional regulation is to determine how multiple signal transduction pathways converge on a single promoter to regulate transcription in divergent fashions. To study this, we have investigated the transcriptional regulation of the Schizosaccharomyces po...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.17.6426-6434.2000
更新日期:2000-09-01 00:00:00
abstract::Sensing of extracellular glucose is necessary for cells to adapt to glucose variation in their environment. In the respiratory yeast Kluyveromyces lactis, extracellular glucose controls the expression of major glucose permease gene RAG1 through a cascade similar to the Saccharomyces cerevisiae Snf3/Rgt2/Rgt1 glucose s...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00515-14
更新日期:2015-02-01 00:00:00
abstract::We measured the content and metabolism of histone mRNA in mouse 3T6 fibroblasts during a serum-induced transition from the resting to growing state. The content of several histone H3 and H2b mRNAs was measured by an S1 nuclease procedure. All of these increase in parallel by a factor of about 50 during S phase. Howeve...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.3.11.1920
更新日期:1983-11-01 00:00:00
abstract::In Drosophila melanogaster, X chromosome dosage compensation is achieved by doubling the transcription of most X-linked genes. The male-specific lethal (MSL) complex is required for this process and binds to hundreds of sites on the male X chromosome. The MSL1 protein is essential for X chromosome binding and serves a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.20.8913-8924.2005
更新日期:2005-10-01 00:00:00
abstract::We sought to study the binding constraints placed on the nine-zinc-finger protein transcription factor IIIA (TFIIIA) by a histone octamer. To this end, five overlapping fragments of the Xenopus laevis oocyte and somatic 5S rRNA genes were reconstituted into nucleosomes, and it was subsequently shown that nucleosome tr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.3.1156
更新日期:1998-03-01 00:00:00
abstract::Compromised immunoregulation contributes to obesity and complications in metabolic pathogenesis. Here, we demonstrate that the nuclear factor of activated T cell (NFAT) group of transcription factors contributes to glucose and insulin homeostasis. Expression of two members of the NFAT family (NFATc2 and NFATc4) is ind...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00580-06
更新日期:2006-10-01 00:00:00
abstract::Keratin 6 (K6) expression in the epidermis has two components: constitutive expression in the innermost layer of the outer root sheath (ORS) of hair follicles and inducible expression in the interfollicular epidermis in response to stressful stimuli such as wounding. Mice express two K6 isoforms, MK6a and MK6b. To gai...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.14.5248-5255.2000
更新日期:2000-07-01 00:00:00
abstract::Mouse neuroblastoma Neuro-2A cells produce transforming growth factors during exponential growth in a defined hormone-free medium, which, on Bio-Gel columns in 1 M HAc, elute at a molecular size of 15 to 20 kilodaltons (kDa). These neuroblastoma-derived transforming growth factors have strong mitogenic activity, but t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.9.2289
更新日期:1985-09-01 00:00:00
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
doi:10.1128/mcb.24.4.1531-1539.2004
更新日期:2004-02-01 00:00:00
abstract::Genetics and in vitro studies have shown that the direct interaction between Gal3p and Gal80p plays a central role in galactose-dependent Gal4p-mediated GAL gene expression in the yeast Saccharomyces cerevisiae. Precisely how Gal3p-Gal80p interaction effects induction is not clear. It has been assumed that Gal3p inter...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.14.5140-5148.2000
更新日期:2000-07-01 00:00:00
abstract::p300 and the closely related CREB binding protein (CBP) are transcriptional adaptors that are present in intracellular complexes with TATA binding protein (TBP) and bind to upstream activators including p53 and nuclear hormone receptors. They have intrinsic and associated histone acetyltransferase activity, suggesting...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.6.3596
更新日期:1998-06-01 00:00:00
abstract::DET1 (de-etiolated 1) is an essential negative regulator of plant light responses, and it is a component of the Arabidopsis thaliana CDD complex containing DDB1 and COP10 ubiquitin E2 variant. Human DET1 has recently been isolated as one of the DDB1- and Cul4A-associated factors, along with an array of WD40-containing...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.02432-06
更新日期:2007-07-01 00:00:00
abstract::The nuclear receptor peroxisome proliferator-activated receptor gamma regulates adipose differentiation and systemic insulin signaling via ligand-dependent transcriptional activation of target genes. However, the identities of the biologically relevant target genes are largely unknown. Here we describe the isolation a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.14.5343-5349.2000
更新日期:2000-07-01 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::Physiological cell deaths occur ubiquitously throughout biology and have common attributes, including apoptotic morphology with mitosis-like chromatin condensation and prelytic genome digestion. The fundamental question is whether a common mechanism of dying underlies these common hallmarks of death. Here we describe ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.5.2912
更新日期:1998-05-01 00:00:00
abstract::During mammalian dosage compensation, one of two X-chromosomes in female cells is inactivated. The choice of which X is silenced can be imprinted or stochastic. Although genetic loci influencing the choice decision have been identified, the primary marks for imprinting and random selection remain undefined. Here, we e...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.6.2109-2117.2006
更新日期:2006-03-01 00:00:00
abstract::Unintended DNA rearrangements in a differentiating lymphocyte can have severe, oncogenic consequences, but the mechanisms for avoiding pathogenic outcomes in V(D)J recombination are not well understood. The first level at which fidelity is instituted is in discrimination by the recombination proteins between authentic...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.14.5032-5040.2000
更新日期:2000-07-01 00:00:00
abstract::SEC62 is required for the import of secretory protein precursors into the endoplasmic reticulum (ER) of Saccharomyces cerevisiae. The DNA sequence of SEC62 predicts a 32-kDa polypeptide with two potential membrane-spanning segments. Two antisera directed against different portions of the SEC62 coding region specifical...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.11.6024
更新日期:1990-11-01 00:00:00
abstract::Mammalian B-cell lymphoid malignancies frequently display aberrant translocations involving the c-myc proto-oncogene and one of the immunoglobulin loci. We have observed and characterized such a translocation in the immunoglobulin E-producing rat immunocytoma IR162 by using recombinant DNA technology. We show here for...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.7.2614
更新日期:1987-07-01 00:00:00
abstract::The chemotropic guidance cue netrin-1 mediates attraction of migrating axons during central nervous system development through the receptor Deleted in Colorectal Cancer (DCC). Downstream of netrin-1, activated Rho GTPases Rac1 and Cdc42 induce cytoskeletal rearrangements within the growth cone. The Rho guanine nucleot...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01264-12
更新日期:2013-02-01 00:00:00
abstract::Revertants were selected from aryl hydrocarbon hydroxylase (AHH)-deficient recessive mutants belonging to three complementation groups and from a dominant mutant of the Hepa-1 cell line. The recessive mutants had low spontaneous reversion frequencies (less than 4 X 10(-7] that were increased by mutagenesis. The majori...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.8.1597
更新日期:1984-08-01 00:00:00
abstract::Neutrophils are first responders rapidly mobilized to inflammatory sites by a tightly regulated, nonredundant hierarchy of chemoattractants. These chemoattractants engage neutrophil cell surface receptors triggering heterotrimeric G-protein Gα(i) subunits to exchange GDP for GTP. By limiting the duration that Gα(i) su...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00651-12
更新日期:2012-11-01 00:00:00