Glycogen synthase kinase 3beta-mediated serine phosphorylation of the human glucocorticoid receptor redirects gene expression profiles.

Abstract:

:Aberrant glycogen synthase kinase 3beta (GSK-3beta) activity is associated with the progression of several pathological conditions such as diabetes, Alzheimer's, and cancer. GSK-3beta regulates cellular processes by directly phosphorylating metabolic enzymes and transcription factors. Here, we discovered a new target for GSK-3beta phosphorylation: the human glucocorticoid receptor (GR). Glucocorticoid signaling is essential for life and regulates diverse biological functions from cell growth to metabolism to apoptosis. Specifically, we found hormone-dependent GR phosphorylation on serine 404 by GSK-3beta. Cells expressing a GR that is incapable of GSK-3beta phosphorylation had a redirection of the global transcriptional response to hormone, including the activation of additional signaling pathways, in part due to the altered ability of unphosphorylatable GR to recruit transcriptional cofactors CBP/p300 and the p65 (RelA) subunit of NF-kappaB. Furthermore, GSK-3beta-mediated GR phosphorylation inhibited glucocorticoid-dependent NF-kappaB transrepression and attenuated the glucocorticoid-dependent cell death of osteoblasts. Collectively, our results describe a novel convergence point of the GSK-3beta and the GR pathways, resulting in altered hormone-regulated signaling. Our results also provide a mechanism by which GSK-3beta activity can dictate how cells will ultimately respond to glucocorticoids.

journal_name

Mol Cell Biol

authors

Galliher-Beckley AJ,Williams JG,Collins JB,Cidlowski JA

doi

10.1128/MCB.00808-08

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

7309-22

issue

24

eissn

0270-7306

issn

1098-5549

pii

MCB.00808-08

journal_volume

28

pub_type

杂志文章
  • Distinctive features of Drosophila alternative splicing factor RS domain: implication for specific phosphorylation, shuttling, and splicing activation.

    abstract::The human splicing factor 2, also called human alternative splicing factor (hASF), is the prototype of the highly conserved SR protein family involved in constitutive and regulated splicing of metazoan mRNA precursors. Here we report that the Drosophila homologue of hASF (dASF) lacks eight repeating arginine-serine di...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.4.1345-1359.2001

    authors: Allemand E,Gattoni R,Bourbon HM,Stevenin J,Cáceres JF,Soret J,Tazi J

    更新日期:2001-02-01 00:00:00

  • Genes activated in the presence of an immunoglobulin enhancer or promoter are negatively regulated by a T-lymphoma cell line.

    abstract::The tissue-specific expression of immunoglobulin genes can be partially explained by a requirement for activating factors found only in B lymphocytes and their derivatives. However, loss of immunoglobulin expression upon fusion of an immunoglobulin-producing myeloma cell with a T lymphoma cell (BW5147) or fibroblast (...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.5.1932

    authors: Zaller DM,Yu H,Eckhardt LA

    更新日期:1988-05-01 00:00:00

  • Correct temperature induction and developmental regulation of a cloned heat shock gene transformed into the Drosophila germ line.

    abstract::We have constructed a size variant of the Drosophila hsp28 gene by deleting 207 base pairs of the protein coding region, beginning 33 base pairs downstream of the ATG protein initiation codon. After transformation of Drosophila melanogaster rosy (ry506) flies with this altered gene, using the P transposable element sy...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.4.12.2883

    authors: Hoffman EP,Corces VG

    更新日期:1984-12-01 00:00:00

  • The conserved ninth C-terminal heptad in thyroid hormone and retinoic acid receptors mediates diverse responses by affecting heterodimer but not homodimer formation.

    abstract::The receptors for thyroid hormone (T3R), all-trans-retinoic acid (RAR), and 9-cis-retinoic acid (RXR) bind DNA response elements as homo- and heterodimers. The ligand-binding domains of these receptors contain nine conserved heptads proposed to play a role in dimerization. Mutant receptors with changes in the first or...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.9.5725

    authors: Au-Fliegner M,Helmer E,Casanova J,Raaka BM,Samuels HH

    更新日期:1993-09-01 00:00:00

  • Increased phosphorylation of tyrosine in vinculin does not occur upon transformation by some avian sarcoma viruses.

    abstract::The level of phosphotyrosine in vinculin was determined in chicken embryo fibroblasts transformed by various strains of avian sarcoma virus. As previously reported (Sefton et al., Cell 24:165-174, 1981), vinculin was phosphorylated at tyrosine residues in most cultures examined, but the level varied greatly and no det...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.1.263

    authors: Antler AM,Greenberg ME,Edelman GM,Hanafusa H

    更新日期:1985-01-01 00:00:00

  • Transcriptional induction of the murine c-rel gene with serum and phorbol-12-myristate-13-acetate in fibroblasts.

    abstract::Transcription of the c-rel proto-oncogene was induced transiently when resting mouse NIH 3T3 fibroblasts were stimulated with serum or phorbol-12-myristate-13-acetate. Addition of cycloheximide increased the steady-state levels of c-rel mRNA. These results indicate that c-rel is another member of the early-response ge...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.11.5239

    authors: Bull P,Hunter T,Verma IM

    更新日期:1989-11-01 00:00:00

  • When Long Noncoding Becomes Protein Coding.

    abstract::Recent advancements in genetic and proteomic technologies have revealed that more of the genome encodes proteins than originally thought possible. Specifically, some putative long noncoding RNAs (lncRNAs) have been misannotated as noncoding. Numerous lncRNAs have been found to contain short open reading frames (sORFs)...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章,评审

    doi:10.1128/MCB.00528-19

    authors: Hartford CCR,Lal A

    更新日期:2020-02-27 00:00:00

  • The capable ABL: what is its biological function?

    abstract::The mammalian ABL1 gene encodes the ubiquitously expressed nonreceptor tyrosine kinase ABL. In response to growth factors, cytokines, cell adhesion, DNA damage, oxidative stress, and other signals, ABL is activated to stimulate cell proliferation or differentiation, survival or death, retraction, or migration. ABL als...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章,评审

    doi:10.1128/MCB.01454-13

    authors: Wang JY

    更新日期:2014-04-01 00:00:00

  • Overlapping functions of the pRb family in the regulation of rRNA synthesis.

    abstract::The "pocket" proteins pRb, p107, and p130 are a family of negative growth regulators. Previous studies have demonstrated that overexpression of pRb can repress transcription by RNA polymerase (Pol) I. To assess whether pRb performs this role under physiological conditions, we have examined pre-rRNA levels in cells fro...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.21.17.5806-5814.2001

    authors: Ciarmatori S,Scott PH,Sutcliffe JE,McLees A,Alzuherri HM,Dannenberg JH,te Riele H,Grummt I,Voit R,White RJ

    更新日期:2001-09-01 00:00:00

  • Expression of HLA-DR antigen in human class II mutant B-cell lines by double infection with retrovirus vectors.

    abstract::A new retrovirus vector containing the gene for hygromycin B resistance (hyg) as a selectable marker under the control of an internal simian virus 40 promoter was constructed. It was used, together with an analogous previously described vector, DO1, which contains the gene for G418 resistance, to introduce and express...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.11.3923

    authors: Yang Z,Korman AJ,Cooper J,Pious D,Accolla RS,Mulligan RC,Strominger JL

    更新日期:1987-11-01 00:00:00

  • Human Schlafen 5 (SLFN5) Is a Regulator of Motility and Invasiveness of Renal Cell Carcinoma Cells.

    abstract::We provide evidence that human SLFN5, an interferon (IFN)-inducible member of the Schlafen (SLFN) family of proteins, exhibits key roles in controlling motility and invasiveness of renal cell carcinoma (RCC) cells. Our studies define the mechanism by which this occurs, demonstrating that SLFN5 negatively controls expr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00019-15

    authors: Sassano A,Mavrommatis E,Arslan AD,Kroczynska B,Beauchamp EM,Khuon S,Chew TL,Green KJ,Munshi HG,Verma AK,Platanias LC

    更新日期:2015-08-01 00:00:00

  • Membrane localization of phosphatidylinositol 3-kinase is sufficient to activate multiple signal-transducing kinase pathways.

    abstract::Phosphatidylinositol (PI) 3-kinase is a cytoplasmic signaling molecule recruited to the membrane by activated growth factor receptors. The p85 subunit of PI 3-kinase links the catalytic p110 subunit to activated growth factor receptors and is required for enzymatic activity of p110. In this report, we describe the eff...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.8.4117

    authors: Klippel A,Reinhard C,Kavanaugh WM,Apell G,Escobedo MA,Williams LT

    更新日期:1996-08-01 00:00:00

  • Identification and characterization of PF4varl, a human gene variant of platelet factor 4.

    abstract::A synthetic DNA probe designed to detect coding sequences for platelet factor 4 and connective tissue-activating peptide III (two human platelet alpha-granule proteins) was used to identify several similar sequences in total human DNA. Sequence analysis of a corresponding 3,201-base-pair EcoRI fragment isolated from a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.4.1445

    authors: Green CJ,Charles RS,Edwards BF,Johnson PH

    更新日期:1989-04-01 00:00:00

  • Type 1 transforming growth factor beta: amplified expression and secretion of mature and precursor polypeptides in Chinese hamster ovary cells.

    abstract::Recombinant type 1 transforming growth factor beta (TGF-beta) was expressed to high levels in CHO cells by using dihydrofolate reductase (dhfr) gene amplification. The expression plasmid was derived from the pSV2 vectors and contained, in tandem, the simian TGF-beta and mouse dhfr cDNAs. Transcription of both cDNAs wa...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.10.3418

    authors: Gentry LE,Webb NR,Lim GJ,Brunner AM,Ranchalis JE,Twardzik DR,Lioubin MN,Marquardt H,Purchio AF

    更新日期:1987-10-01 00:00:00

  • Overexpression of protein kinase C in HT29 colon cancer cells causes growth inhibition and tumor suppression.

    abstract::By using a retrovirus-derived vector system, we generated derivatives of the human colon cancer cell line HT29 that stably overexpress a full-length cDNA encoding the beta 1 isoform of rat protein kinase C (PKC). Two of these cell lines, PKC6 and PKC7, displayed an 11- to 15-fold increase in PKC activity when compared...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.9.4650

    authors: Choi PM,Tchou-Wong KM,Weinstein IB

    更新日期:1990-09-01 00:00:00

  • Repression of c-myc is necessary but not sufficient for terminal differentiation of B lymphocytes in vitro.

    abstract::The importance of c-myc as a target of the Blimp-1 repressor has been studied in BCL-1 cells, in which Blimp-1 is sufficient to trigger terminal B-cell differentiation. Our data show that Blimp-1-dependent repression of c-myc is required for BCL-1 differentiation, since constitutive expression of c-Myc blocked differe...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.23.8684-8695.2000

    authors: Lin KI,Lin Y,Calame K

    更新日期:2000-12-01 00:00:00

  • Purification and characterization of nucleolin and its identification as a transcription repressor.

    abstract::Expression of the acute-phase response genes, such as that for alpha-1 acid glycoprotein (AGP), involves both positive and negative transcription factors. A positive transcription factor, AGP/EBP, and a negative transcription factor, factor B, have been identified as the two most important factors responsible for the ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.9.6068

    authors: Yang TH,Tsai WH,Lee YM,Lei HY,Lai MY,Chen DS,Yeh NH,Lee SC

    更新日期:1994-09-01 00:00:00

  • Unique role for the UbL-UbA protein Ddi1 in turnover of SCFUfo1 complexes.

    abstract::SCF complexes are E3 ubiquitin-protein ligases that mediate degradation of regulatory and signaling proteins and control G1/S cell cycle progression by degradation of G1 cyclins and the cyclin-dependent kinase inhibitor, Sic1. Interchangeable F-box proteins bind the core SCF components; each recruits a specific subset...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.26.5.1579-1588.2006

    authors: Ivantsiv Y,Kaplun L,Tzirkin-Goldin R,Shabek N,Raveh D

    更新日期:2006-03-01 00:00:00

  • Novel splicing factor RBM25 modulates Bcl-x pre-mRNA 5' splice site selection.

    abstract::RBM25 has been shown to associate with splicing cofactors SRm160/300 and assembled splicing complexes, but little is known about its splicing regulation. Here, we characterize the functional role of RBM25 in alternative pre-mRNA splicing. Increased RBM25 expression correlated with increased apoptosis and specifically ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00560-08

    authors: Zhou A,Ou AC,Cho A,Benz EJ Jr,Huang SC

    更新日期:2008-10-01 00:00:00

  • Postcleavage sequence specificity in V(D)J recombination.

    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

    authors: Agard EA,Lewis SM

    更新日期:2000-07-01 00:00:00

  • DOT4 links silencing and cell growth in Saccharomyces cerevisiae.

    abstract::Transcriptional silencing in Saccharomyces cerevisiae occurs at specific loci and is mediated by a multiprotein complex that includes Rap1p and the Sir proteins. We studied the function of a recently identified gene, DOT4, that disrupts silencing when overexpressed. DOT4 encodes an ubiquitin processing protease (hydro...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.10.6608

    authors: Kahana A,Gottschling DE

    更新日期:1999-10-01 00:00:00

  • Regulation of the protein kinase PKR by the vaccinia virus pseudosubstrate inhibitor K3L is dependent on residues conserved between the K3L protein and the PKR substrate eIF2alpha.

    abstract::The mammalian double-stranded RNA-activated protein kinase PKR is a component of the cellular antiviral defense mechanism and phosphorylates Ser-51 on the alpha subunit of the translation factor eIF2 to inhibit protein synthesis. To identify the molecular determinants that specify substrate recognition by PKR, we perf...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.7.4146

    authors: Kawagishi-Kobayashi M,Silverman JB,Ung TL,Dever TE

    更新日期:1997-07-01 00:00:00

  • Increased DNA damage sensitivity and apoptosis in cells lacking the Snf5/Ini1 subunit of the SWI/SNF chromatin remodeling complex.

    abstract::The gene encoding the SNF5/Ini1 core subunit of the SWI/SNF chromatin remodeling complex is a tumor suppressor in humans and mice, with an essential role in early embryonic development. To investigate further the function of this gene, we have generated a Cre/lox-conditional mouse line. We demonstrate that Snf5 deleti...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.26.7.2661-2674.2006

    authors: Klochendler-Yeivin A,Picarsky E,Yaniv M

    更新日期:2006-04-01 00:00:00

  • Skp2B stimulates mammary gland development by inhibiting REA, the repressor of the estrogen receptor.

    abstract::Skp2B, an F-box protein of unknown function, is frequently overexpressed in breast cancer. In order to determine the function of Skp2B and whether it has a role in breast cancer, we performed a two-hybrid screen and established transgenic mice expressing Skp2B in the mammary glands. We found that Skp2B interacts with ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01239-07

    authors: Umanskaya K,Radke S,Chander H,Monardo R,Xu X,Pan ZQ,O'Connell MJ,Germain D

    更新日期:2007-11-01 00:00:00

  • c-ABL tyrosine kinase activity is regulated by association with a novel SH3-domain-binding protein.

    abstract::The c-ABL tyrosine kinase is activated following either the loss or mutation of its Src homology domain 3 (SH3), resulting in both increased autophosphorylation and phosphorylation of cellular substrates and cellular transformation. This suggests that the SH3 domain negatively regulates c-ABL kinase activity. For seve...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.12.7054

    authors: Zhu J,Shore SK

    更新日期:1996-12-01 00:00:00

  • A critical role for the Wnt effector Tcf4 in adult intestinal homeostatic self-renewal.

    abstract::Throughout life, intestinal Lgr5+ stem cells give rise to proliferating transient amplifying cells in crypts, which subsequently differentiate into one of the five main cell types and migrate along the crypt-villus axis. These dynamic processes are coordinated by a relatively small number of evolutionarily conserved s...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.06288-11

    authors: van Es JH,Haegebarth A,Kujala P,Itzkovitz S,Koo BK,Boj SF,Korving J,van den Born M,van Oudenaarden A,Robine S,Clevers H

    更新日期:2012-05-01 00:00:00

  • Multiple proteins interact with the fushi tarazu proximal enhancer.

    abstract::The expression of the Drosophila segmentation gene fushi tarazu (ftz) is controlled at the level of transcription. The proximal enhancer, located approximately 3.4 kb upstream of the transcription start site, directs lacZ fusion gene expression in a ftz-like seven-stripe pattern in transgenic fly embryos. We have take...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.9.5549

    authors: Han W,Yu Y,Altan N,Pick L

    更新日期:1993-09-01 00:00:00

  • Molecular cloning of casein kinase II alpha subunit from Dictyostelium discoideum and its expression in the life cycle.

    abstract::A Dictyostelium discoideum cDNA encoding an alpha-type subunit of casein kinase II was isolated, and its cDNA was used to study developmental expression of casein kinase II during the Dictyostelium life cycle. The 1.3-kb cDNA insert contained an open reading frame of 337 amino acids (M(r) 39,900). The deduced amino ac...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.12.5711

    authors: Kikkawa U,Mann SK,Firtel RA,Hunter T

    更新日期:1992-12-01 00:00:00

  • Autoregulation of interleukin 6 and granulocyte-macrophage colony-stimulating factor in the differentiation of myeloid leukemic cells.

    abstract::Induction of differentiation in one type of clone of mouse myeloid leukemic cells by mouse or human interleukin 6 (IL-6) and in another type of clone by mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) was found to be associated with induction of IL-6 and GM-CSF mRNA and protein. The results indicated t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.9.4109

    authors: Shabo Y,Lotem J,Sachs L

    更新日期:1989-09-01 00:00:00

  • Two conserved amino acid motifs mediate protein targeting to the micronemes of the apicomplexan parasite Toxoplasma gondii.

    abstract::The micronemal protein 2 (MIC2) of Toxoplasma gondii shares sequence and structural similarities with a series of adhesive molecules of different apicomplexan parasites. These molecules accumulate, through a yet unknown mechanism, in secretory vesicles (micronemes), which together with tubular and membrane structures ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.19.7332-7341.2000

    authors: Di Cristina M,Spaccapelo R,Soldati D,Bistoni F,Crisanti A

    更新日期:2000-10-01 00:00:00