Gab1 is an integrator of cell death versus cell survival signals in oxidative stress.

Abstract:

:Upon the addition of different growth factors and cytokines, the Gab1 docking protein is tyrosine phosphorylated and in turn activates different signaling pathways. On the basis of the large body of evidence concerning cross talk between the signaling pathways activated by growth factors and oxidative stress, we decided to investigate the role of Gab1 in oxidative injury. We stimulated wild-type mouse embryo fibroblasts (MEF) or MEF with a homozygous deletion of the Gab1 gene (-/- MEF) with H(2)O(2). Our results show that Gab1 is phosphorylated in a dose- and time-dependent manner after H(2)O(2) triggering. Gab1 then recruits molecules such as SHP2, phosphatidylinositol 3-kinase (PI3K), and Shc. Gab1 phosphorylation is sensitive to the Src family kinase inhibitor PP2. Furthermore, we demonstrate that Gab1 is required for H(2)O(2)-induced c-Jun N-terminal kinase (JNK) activation but not for ERK2 or p38 activation. Reconstitution of Gab1 in -/- MEF rescues JNK activation, and we find that this is dependent on the SHP2 binding site in Gab1. Cell viability assays reveal that Gab1 has a dual role in cell survival: a positive one through its interaction with PI3K and a negative one through its interaction with SHP2. This is the first report identifying Gab1 as a component in oxidative stress signaling and one that is required for JNK activation.

journal_name

Mol Cell Biol

authors

Holgado-Madruga M,Wong AJ

doi

10.1128/mcb.23.13.4471-4484.2003

subject

Has Abstract

pub_date

2003-07-01 00:00:00

pages

4471-84

issue

13

eissn

0270-7306

issn

1098-5549

journal_volume

23

pub_type

杂志文章
  • Hepatic Overexpression of CD36 Improves Glycogen Homeostasis and Attenuates High-Fat Diet-Induced Hepatic Steatosis and Insulin Resistance.

    abstract::The common complications in obesity and type 2 diabetes include hepatic steatosis and disruption of glucose-glycogen homeostasis, leading to hyperglycemia. Fatty acid translocase (FAT/CD36), whose expression is inducible in obesity, is known for its function in fatty acid uptake. Previous work by us and others suggest...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00138-16

    authors: Garbacz WG,Lu P,Miller TM,Poloyac SM,Eyre NS,Mayrhofer G,Xu M,Ren S,Xie W

    更新日期:2016-10-13 00:00:00

  • Recruitment of the extracellular signal-regulated kinase/ribosomal S6 kinase signaling pathway to the NFATc4 transcription activation complex.

    abstract::Integration of protein kinases into transcription activation complexes influences the magnitude of gene expression. The nuclear factor of activated T cells (NFAT) group of proteins are critical transcription factors that direct gene expression in immune and nonimmune cells. A balance of phosphotransferase activity is ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.3.907-920.2005

    authors: Yang TT,Xiong Q,Graef IA,Crabtree GR,Chow CW

    更新日期:2005-02-01 00:00:00

  • TATA-binding protein and associated factors in polymerase II and polymerase III transcription.

    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

    authors: Meyers RE,Sharp PA

    更新日期:1993-12-01 00:00:00

  • Phenotypic analysis of mice deficient in the type 2 galanin receptor (GALR2).

    abstract::Galanin is a neuropeptide implicated in the regulation of feeding, reproduction, cognition, nociception, and seizure susceptibility. There are three known galanin receptor (GALR) subtypes (GALR1, GALR2, and GALR3), which bind to galanin with different affinities and have their own unique distributions, signaling mecha...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.11.4804-4811.2005

    authors: Gottsch ML,Zeng H,Hohmann JG,Weinshenker D,Clifton DK,Steiner RA

    更新日期:2005-06-01 00:00:00

  • Site-directed perturbation of protein kinase C- integrin interaction blocks carcinoma cell chemotaxis.

    abstract::Polarized cell movement is an essential requisite for cancer metastasis; thus, interference with the tumor cell motility machinery would significantly modify its metastatic behavior. Protein kinase C alpha (PKC alpha) has been implicated in the promotion of a migratory cell phenotype. We report that the phorbol ester-...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.16.5897-5911.2002

    authors: Parsons M,Keppler MD,Kline A,Messent A,Humphries MJ,Gilchrist R,Hart IR,Quittau-Prevostel C,Hughes WE,Parker PJ,Ng T

    更新日期:2002-08-01 00:00:00

  • Sterol regulatory element binding protein 1a regulates hepatic fatty acid partitioning by activating acetyl coenzyme A carboxylase 2.

    abstract::We generated a line of mice in which sterol regulatory element binding protein 1a (SREBP-1a) was specifically inactivated by insertional mutagenesis. Homozygous mutant mice were completely viable despite expressing SREBP-1a mRNA below 5% of normal, and there were minimal effects on expression of either SREBP-1c or -2....

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00553-09

    authors: Im SS,Hammond LE,Yousef L,Nugas-Selby C,Shin DJ,Seo YK,Fong LG,Young SG,Osborne TF

    更新日期:2009-09-01 00:00:00

  • The yeast EUG1 gene encodes an endoplasmic reticulum protein that is functionally related to protein disulfide isomerase.

    abstract::The product of the EUG1 gene of Saccharomyces cerevisiae is a soluble endoplasmic reticulum protein with homology to both the mammalian protein disulfide isomerase (PDI) and the yeast PDI homolog encoded by the essential PDI1 gene. Deletion or overexpression of EUG1 causes no growth defects under a variety of conditio...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.10.4601

    authors: Tachibana C,Stevens TH

    更新日期:1992-10-01 00:00:00

  • The Rb-related p107 protein can suppress E2F function independently of binding to cyclin A/cdk2.

    abstract::The interaction of the retinoblastoma susceptibility gene product (Rb)-related p107 protein with the E2F transcription factor in S-phase cells facilitates the formation of a multicomponent complex also containing cyclin A and the p33cdk2 kinase. We have created a series of p107 mutants to assess the ability of p107 to...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.1.338

    authors: Smith EJ,Nevins JR

    更新日期:1995-01-01 00:00:00

  • Phosphorylation of C/EBPalpha inhibits granulopoiesis.

    abstract::CCAAT/enhancer-binding protein alpha (C/EBPalpha) is one of the key transcription factors that mediate lineage specification and differentiation of multipotent myeloid progenitors into mature granulocytes. Although C/EBPalpha is known to induce granulopoiesis while suppressing monocyte differentiation, it is unclear h...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.24.2.675-686.2004

    authors: Ross SE,Radomska HS,Wu B,Zhang P,Winnay JN,Bajnok L,Wright WS,Schaufele F,Tenen DG,MacDougald OA

    更新日期:2004-01-01 00:00:00

  • Requirement of Phosphoinositides Containing Stearic Acid To Control Cell Polarity.

    abstract::Phosphoinositides (PIPs) are present in very small amounts but are essential for cell signaling, morphogenesis, and polarity. By mass spectrometry, we demonstrated that some PIPs with stearic acyl chains were strongly disturbed in a psi1Δ Saccharomyces cerevisiae yeast strain deficient in the specific incorporation of...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00843-15

    authors: Doignon F,Laquel P,Testet E,Tuphile K,Fouillen L,Bessoule JJ

    更新日期:2016-02-16 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

  • Selective translational regulation of ribosomal protein gene expression during early development of Drosophila melanogaster.

    abstract::We have previously characterized a cloned cDNA coding for a developmentally regulated mRNA in Drosophila melanogaster whose expression is selectively regulated at the translational level during oogenesis and embryogenesis. In this report we show that this translationally regulated mRNA (rpA1) codes for an acidic ribos...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.12.3583

    authors: Kay MA,Jacobs-Lorena M

    更新日期:1985-12-01 00:00:00

  • Shared pathways of IkappaB kinase-induced SCF(betaTrCP)-mediated ubiquitination and degradation for the NF-kappaB precursor p105 and IkappaBalpha.

    abstract::p105 (NFKB1) acts in a dual way as a cytoplasmic IkappaB molecule and as the source of the NF-kappaB p50 subunit upon processing. p105 can form various heterodimers with other NF-kappaB subunits, including its own processing product, p50, and these complexes are signal responsive. Signaling through the IkappaB kinase ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.4.1024-1035.2001

    authors: Heissmeyer V,Krappmann D,Hatada EN,Scheidereit C

    更新日期:2001-02-01 00:00:00

  • 2-Aminopurine selectively inhibits splicing of tumor necrosis factor alpha mRNA.

    abstract::2-Aminopurine (2-AP) inhibits specific kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor 2. One of these, PKR, is also involved in signal transduction. We show here that 2-AP selectively inhibits expression of tumor necrosis factor alpha (TNF-alpha) mRNA in primary human lymphoid...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.6.2814

    authors: Jarrous N,Osman F,Kaempfer R

    更新日期:1996-06-01 00:00:00

  • FOXN1 Transcription Factor in Epithelial Growth and Wound Healing.

    abstract::FOXN1 is a prodifferentiation transcription factor in the skin epithelium. Recently, it has also emerged as an important player in controlling the skin wound healing process, as it actively participates in reepithelialization and is thought to be responsible for scar formation. FOXN1 positivity is also a feature of pi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章,评审

    doi:10.1128/MCB.00110-17

    authors: Grabowska AI,Wilanowski T

    更新日期:2017-08-11 00:00:00

  • Altered RNA editing in mice lacking ADAR2 autoregulation.

    abstract::ADAR2 is a double-stranded-RNA-specific adenosine deaminase involved in the editing of mammalian RNAs by the site-selective conversion of adenosine to inosine. Previous studies from our laboratory have demonstrated that ADAR2 can modify its own pre-mRNA to create a proximal 3' splice site containing a noncanonical ade...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.26.2.480-488.2006

    authors: Feng Y,Sansam CL,Singh M,Emeson RB

    更新日期:2006-01-01 00:00:00

  • Characterization of Neurospora CPC1, a bZIP DNA-binding protein that does not require aligned heptad leucines for dimerization.

    abstract::CPC1 is the transcriptional activator of amino acid biosynthetic genes of Neurospora crassa. CPC1 function in vivo was abolished upon deletion of segments of cpc-1 corresponding to the presumed transcription activation domain, the DNA-binding and dimerization domains, or a 52-residue connector segment of CPC1. A trunc...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.2.935

    authors: Paluh JL,Yanofsky C

    更新日期:1991-02-01 00:00:00

  • The a-factor pheromone of Saccharomyces cerevisiae is essential for mating.

    abstract::The Saccharomyces cerevisiae pheromone a-factor is produced by a cells and interacts with alpha cells to cause cell cycle arrest and other physiological responses associated with mating. Two a-factor structural genes, MFA1 and MFA2, have been previously cloned with synthetic probes based on the a-factor amino acid seq...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.3.1309

    authors: Michaelis S,Herskowitz I

    更新日期:1988-03-01 00:00:00

  • Six mouse alpha-tubulin mRNAs encode five distinct isotypes: testis-specific expression of two sister genes.

    abstract::Five mouse alpha-tubulin isotypes are described, each distinguished by the presence of unique amino acid substitutions within the coding region. Most, though not all of these isotype-specific amino acids, are clustered at the carboxy terminus. One of the alpha-tubulin isotypes described is expressed exclusively in tes...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.7.2409

    authors: Villasante A,Wang D,Dobner P,Dolph P,Lewis SA,Cowan NJ

    更新日期:1986-07-01 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

  • Characterization of VSG gene expression site promoters and promoter-associated DNA rearrangement events.

    abstract::The expressed variant cell surface glycoprotein (VSG) gene of Trypanosoma brucei is located at the 3' end of a large, telomeric, polycistronic transcription unit or expression site. We show that the region 45 kb upstream of the VSG gene, in the expression site on a 1.5-Mb chromosome, contains at least two promoters th...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.5.2467

    authors: Gottesdiener K,Chung HM,Brown SD,Lee MG,Van der Ploeg LH

    更新日期:1991-05-01 00:00:00

  • Analysis of TFIIA function In vivo: evidence for a role in TATA-binding protein recruitment and gene-specific activation.

    abstract::Activation of transcription can occur by the facilitated recruitment of TFIID to promoters by gene-specific activators. To investigate the role of TFIIA in TFIID recruitment in vivo, we exploited a class of yeast TATA-binding protein (TBP) mutants that is activation and DNA binding defective. We found that co-overexpr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.12.8673

    authors: Liu Q,Gabriel SE,Roinick KL,Ward RD,Arndt KM

    更新日期:1999-12-01 00:00:00

  • A novel colonic repressor element regulates intestinal gene expression by interacting with Cux/CDP.

    abstract::Intestinal gene regulation involves mechanisms that direct temporal expression along the vertical and horizontal axes of the alimentary tract. Sucrase-isomaltase (SI), the product of an enterocyte-specific gene, exhibits a complex pattern of expression. Generation of transgenic mice with a mutated SI transgene showed ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.15.5467-5478.2002

    authors: Boudreau F,Rings EH,Swain GP,Sinclair AM,Suh ER,Silberg DG,Scheuermann RH,Traber PG

    更新日期:2002-08-01 00:00:00

  • Acetylation of p53 at lysine 373/382 by the histone deacetylase inhibitor depsipeptide induces expression of p21(Waf1/Cip1).

    abstract::Generally, histone deacetylase (HDAC) inhibitor-induced p21(Waf1/Cip1) expression is thought to be p53 independent. Here we found that an inhibitor of HDAC, depsipeptide (FR901228), but not trichostatin A (TSA), induces p21(Waf1/Cip1) expression through both p53 and Sp1/Sp3 pathways in A549 cells (which retain wild-ty...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.26.7.2782-2790.2006

    authors: Zhao Y,Lu S,Wu L,Chai G,Wang H,Chen Y,Sun J,Yu Y,Zhou W,Zheng Q,Wu M,Otterson GA,Zhu WG

    更新日期:2006-04-01 00:00:00

  • Overlapping specificities of base excision repair, nucleotide excision repair, recombination, and translesion synthesis pathways for DNA base damage in Saccharomyces cerevisiae.

    abstract::The removal of oxidative damage from Saccharomyces cerevisiae DNA is thought to be conducted primarily through the base excision repair pathway. The Escherichia coli endonuclease III homologs Ntg1p and Ntg2p are S. cerevisiae N-glycosylase-associated apurinic/apyrimidinic (AP) lyases that recognize a wide variety of d...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.4.2929

    authors: Swanson RL,Morey NJ,Doetsch PW,Jinks-Robertson S

    更新日期:1999-04-01 00:00:00

  • Steps in assembly of silent chromatin in yeast: Sir3-independent binding of a Sir2/Sir4 complex to silencers and role for Sir2-dependent deacetylation.

    abstract::Transcriptional silencing at the budding yeast silent mating type (HM) loci and telomeric DNA regions requires Sir2, a conserved NAD-dependent histone deacetylase, Sir3, Sir4, histones H3 and H4, and several DNA-binding proteins. Silencing at the yeast ribosomal DNA (rDNA) repeats requires a complex containing Sir2, N...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.12.4167-4180.2002

    authors: Hoppe GJ,Tanny JC,Rudner AD,Gerber SA,Danaie S,Gygi SP,Moazed D

    更新日期:2002-06-01 00:00:00

  • Activation of yeast polymerase II transcription by herpesvirus VP16 and GAL4 derivatives in vitro.

    abstract::Fusion proteins known to activate transcription in vivo were tested for the ability to stimulate transcription in vitro in a recently developed Saccharomyces cerevisiae RNA polymerase II transcription system. One fusion protein, whose activation domain was derived from the herpesvirus transcriptional activator VP16, g...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.11.4746

    authors: Chasman DI,Leatherwood J,Carey M,Ptashne M,Kornberg RD

    更新日期:1989-11-01 00:00:00

  • Capn5 is expressed in a subset of T cells and is dispensable for development.

    abstract::The Capn5 gene was inactivated by homologous recombination in ES cells that subsequently colonized the germ line of mice. The targeted mutation integrated a lacZ expression cassette into the Capn5 gene, allowing the expression of Capn5 mRNA to be examined in detail in heterozygous animals. Expression was observed in e...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.24.4.1649-1654.2004

    authors: Franz T,Winckler L,Boehm T,Dear TN

    更新日期:2004-02-01 00:00:00

  • Interleukin-7 retroviruses transform pre-B cells by an autocrine mechanism not evident in Abelson murine.

    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

    authors: Overell RW,Clark L,Lynch D,Jerzy R,Schmierer A,Weisser KE,Namen AE,Goodwin RG

    更新日期:1991-03-01 00:00:00

  • Altered beta-actin gene expression in phorbol myristate acetate-treated chondrocytes and fibroblasts.

    abstract::Phorbol-12-myristate-13-acetate (PMA), a potent tumor promoter, was shown to have opposite effects on the cellular morphology and steady-state levels of beta-actin mRNA in embryonic chicken muscle fibroblasts and sternal chondrocytes. When fibroblasts were treated with PMA, they formed foci of densely packed cells, ce...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.6.1425

    authors: Gerstenfeld LC,Finer MH,Boedtker H

    更新日期:1985-06-01 00:00:00