Concerted functions of Gab1 and Shp2 in liver regeneration and hepatoprotection.

Abstract:

:Liver regeneration is a rapid and concerted response to injury, in which growth factor-generated intracellular signals result in activation of transcription factors, DNA synthesis, and hepatocyte proliferation. However, the link between cytoplasmic signals resulting in proliferative response to liver injury remains to be elucidated. We show here that association of Gab1 adaptor protein and Shp2 tyrosine phosphatase is a critical event at the early phase of liver regeneration. Partial hepatectomy (PH) rapidly and transiently induced assembly of a complex comprising Shp2 and tyrosine-phosphorylated Gab1 in wild-type hepatocytes. Consistently, liver-specific Shp2 knockout (LSKO) and liver-specific Gab1 knockout (LGKO) mice displayed very similar phenotypes of defective liver regeneration triggered by PH, including blunted extracellular signal-regulated kinase 1/2 (Erk1/2) activation, decreased expression of immediate-early genes, and reduced levels of cyclins A, E, and B1, as well as suppression of hepatocyte proliferation. In contrast, the Akt and interleukin-6/Stat3 pathways were up-regulated posthepatectomy in LSKO and LGKO mice, accompanied by improved hepatoprotection. Collectively, this study establishes the physiological significance of the Gab1/Shp2 link in promoting mitogenic signaling through the Erk pathway in mammalian liver regeneration.

journal_name

Mol Cell Biol

authors

Bard-Chapeau EA,Yuan J,Droin N,Long S,Zhang EE,Nguyen TV,Feng GS

doi

10.1128/MCB.02253-05

subject

Has Abstract

pub_date

2006-06-01 00:00:00

pages

4664-74

issue

12

eissn

0270-7306

issn

1098-5549

pii

26/12/4664

journal_volume

26

pub_type

杂志文章
  • Identification of phosphotyrosine-containing proteins in untransformed and Rous sarcoma virus-transformed chicken embryo fibroblasts.

    abstract::Phosphorylation on tyrosine residues mediated by pp60src appears to be a primary biochemical event leading to the establishment of the transformed phenotype in Rous sarcoma virus (RSV)-infected cells. To identify the cellular proteins that undergo tyrosine phosphorylation during transformation, a 32P-labeled RSV-trans...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.2.6.653

    authors: Martinez R,Nakamura KD,Weber MJ

    更新日期:1982-06-01 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

  • Conservation of glutamine-rich transactivation function between yeast and humans.

    abstract::Several eukaryotic transcription factors such as Sp1 or Oct1 contain glutamine-rich domains that mediate transcriptional activation. In human cells, promoter-proximally bound glutamine-rich activation domains activate transcription poorly in the absence of acidic type activators bound at distal enhancers, but synergis...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.8.2774-2782.2000

    authors: Escher D,Bodmer-Glavas M,Barberis A,Schaffner W

    更新日期:2000-04-01 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

  • Localization of a highly divergent mammalian testicular alpha tubulin that is not detectable in brain.

    abstract::Sequence analysis of a mouse testicular alpha-tubulin partial cDNA, pRD alpha TT1, reveals an isotype that differs from both the somatic and the predominant testicular alpha tubulins at approximately 30% of the 212 amino acid residues determined. Although this mouse testicular cDNA retains the highly conserved sequenc...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.2.996

    authors: Hecht NB,Distel RJ,Yelick PC,Tanhauser SM,Driscoll CE,Goldberg E,Tung KS

    更新日期:1988-02-01 00:00:00

  • DNA-binding and -bending activities of SAP30L and SAP30 are mediated by a zinc-dependent module and monophosphoinositides.

    abstract::Deacetylation of histones is carried out by a corepressor complex in which Sin3A is an essential scaffold protein. Two proteins in this complex, the Sin3A-associated proteins SAP30L and SAP30, have previously been suggested to function as linker molecules between various corepressors. In this report, we demonstrate ne...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01213-08

    authors: Viiri KM,Jänis J,Siggers T,Heinonen TY,Valjakka J,Bulyk ML,Mäki M,Lohi O

    更新日期:2009-01-01 00:00:00

  • Cotranscriptional recognition of human intronic box H/ACA snoRNAs occurs in a splicing-independent manner.

    abstract::Processing from pre-mRNA introns is a widespread mechanism to generate human box C/D and H/ACA snoRNAs. Recent studies revealed that an optimal position relative to the 3' splice site is important for efficient processing of most box C/D snoRNAs and that assembly of box C/D snoRNPs is stimulated by splicing factors li...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.26.7.2540-2549.2006

    authors: Richard P,Kiss AM,Darzacq X,Kiss T

    更新日期:2006-04-01 00:00:00

  • The Isw2 chromatin-remodeling ATPase cooperates with the Fkh2 transcription factor to repress transcription of the B-type cyclin gene CLB2.

    abstract::Forkhead (Fkh) transcription factors influence cell death, proliferation, and differentiation and the cell cycle. In Saccharomyces cerevisiae, Fkh2 both activates and represses transcription of CLB2, encoding a B-type cyclin. CLB2 is expressed during G(2)/M phase and repressed during G(1). Fkh2 recruits the coactivato...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01798-06

    authors: Sherriff JA,Kent NA,Mellor J

    更新日期:2007-04-01 00:00:00

  • Transcription mediated by NFAT is highly inducible in effector CD4+ T helper 2 (Th2) cells but not in Th1 cells.

    abstract::Transcriptional factors of the NFAT family play an important role in regulating the expression of several cytokine genes during the immune response, such as the genes for interleukin 2 (IL-2) and IL-4, among others. Upon antigen stimulation, precursor CD4+ T helper (pTh) cells proliferate and differentiate into two po...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.3.1522

    authors: Rincón M,Flavell RA

    更新日期:1997-03-01 00:00:00

  • Mouse disabled 1 regulates the nuclear position of neurons in a Drosophila eye model.

    abstract::Nucleokinesis has recently been suggested as a critical regulator of neuronal migration. Here we show that Disabled 1 (Dab1), which is required for neuronal positioning in mammals, regulates the nuclear position of postmitotic neurons in a phosphorylation-site dependent manner. Dab1 expression in the Drosophila visual...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.26.4.1510-1517.2006

    authors: Pramatarova A,Ochalski PG,Lee CH,Howell BW

    更新日期:2006-02-01 00:00:00

  • Differential transactivation by the p53 transcription factor is highly dependent on p53 level and promoter target sequence.

    abstract::Little is known about the mechanisms that regulate differential transactivation by p53. We developed a system in the yeast Saccharomyces cerevisiae that addresses p53 transactivation capacity from 26 different p53 response elements (REs) under conditions where all other factors, such as chromatin, are kept constant. T...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.24.8612-8625.2002

    authors: Inga A,Storici F,Darden TA,Resnick MA

    更新日期:2002-12-01 00:00:00

  • HMGA1 levels influence mitochondrial function and mitochondrial DNA repair efficiency.

    abstract::HMGA chromatin proteins, a family of gene regulatory factors found at only low concentrations in normal cells, are almost universally overexpressed in cancer cells. HMGA proteins are located in the nuclei of normal cells except during the late S/G(2) phases of the cell cycle, when HMGA1, one of the members of the fami...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00105-09

    authors: Mao L,Wertzler KJ,Maloney SC,Wang Z,Magnuson NS,Reeves R

    更新日期:2009-10-01 00:00:00

  • The host gene for intronic U17 small nucleolar RNAs in mammals has no protein-coding potential and is a member of the 5'-terminal oligopyrimidine gene family.

    abstract::Intron-encoded U17a and U17b RNAs are members of the H/ACA-box class of small nucleolar RNAs (snoRNAs) participating in rRNA processing and modification. We have investigated the organization and expression of the U17 locus in human cells and found that intronic U17a and U17b sequences are transcribed as part of the t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.8.4509

    authors: Pelczar P,Filipowicz W

    更新日期:1998-08-01 00:00:00

  • N-cadherin and keratinocyte growth factor receptor mediate the functional interplay between Ki-RASG12V and p53V143A in promoting pancreatic cell migration, invasion, and tissue architecture disruption.

    abstract::The genetic basis of pancreatic ductal adenocarcinoma, which constitutes the most common type of pancreatic malignancy, involves the sequential activation of oncogenes and inactivation of tumor suppressor genes. Among the pivotal genetic alterations are Ki-RAS oncogene activation and p53 tumor suppressor gene inactiva...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01055-05

    authors: Deramaudt TB,Takaoka M,Upadhyay R,Bowser MJ,Porter J,Lee A,Rhoades B,Johnstone CN,Weissleder R,Hingorani SR,Mahmood U,Rustgi AK

    更新日期:2006-06-01 00:00:00

  • Cloning of Saccharomyces cerevisiae DNA replication genes: isolation of the CDC8 gene and two genes that compensate for the cdc8-1 mutation.

    abstract::The CDC8 gene, whose product is required for DNA replication in Saccharomyces cerevisiae, has been isolated on recombinant plasmids. The yeast vector YCp50 bearing the yeast ARS1, CEN4, and URA3 sequences, to provide for replication, stability, and selection, respectively, was used to prepare a recombinant plasmid poo...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.3.10.1730

    authors: Kuo CL,Campbell JL

    更新日期:1983-10-01 00:00:00

  • Analysis of mice with single and multiple copies of transgenes reveals a novel arrangement for the lambda5-VpreB1 locus control region.

    abstract::The murine lambda5-VpreB1 locus encodes two proteins that form part of the pre-B-cell receptor and play a key role in B-lymphocyte development. We have identified a locus control region (LCR) which is responsible for coordinate activation of both genes in pre-B cells. Analysis of mice with single and multiple copies o...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.1.671

    authors: Sabbattini P,Georgiou A,Sinclair C,Dillon N

    更新日期:1999-01-01 00:00:00

  • DNA damage induction of ribonucleotide reductase.

    abstract::RNR2 encodes the small subunit of ribonucleotide reductase, the enzyme that catalyzes the first step in the pathway for the production of deoxyribonucleotides needed for DNA synthesis. RNR2 is a member of a group of genes whose activities are cell cycle regulated and that are transcriptionally induced in response to t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.11.4932

    authors: Elledge SJ,Davis RW

    更新日期:1989-11-01 00:00:00

  • Effects of the SANT domain of tension-induced/inhibited proteins (TIPs), novel partners of the histone acetyltransferase p300, on p300 activity and TIP-6-induced adipogenesis.

    abstract::We previously identified a set of transcription regulators, referred to as TIPs (tension-induced/inhibited proteins), with a role in myogenic versus adipogenic differentiation. Here we report that the TIP family comprises eight isoforms, all bearing a SANT (switching-defective protein 3, adaptor 2, nuclear receptor co...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00333-08

    authors: Badri KR,Zhou Y,Dhru U,Aramgam S,Schuger L

    更新日期:2008-10-01 00:00:00

  • Targeted histone acetylation at the yeast CUP1 promoter requires the transcriptional activator, the TATA boxes, and the putative histone acetylase encoded by SPT10.

    abstract::The relationship between chromatin remodeling and histone acetylation at the yeast CUP1 gene was addressed. CUP1 encodes a metallothionein required for cell growth at high copper concentrations. Induction of CUP1 with copper resulted in targeted acetylation of both H3 and H4 at the CUP1 promoter. Nucleosomes containin...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.18.6406-6416.2002

    authors: Shen CH,Leblanc BP,Neal C,Akhavan R,Clark DJ

    更新日期:2002-09-01 00:00:00

  • The yeast PH domain proteins Slm1 and Slm2 are targets of sphingolipid signaling during the response to heat stress.

    abstract::The PH domain-containing proteins Slm1 and Slm2 were previously identified as effectors of the phosphatidylinositol-4,5-bisphosphate (PI4,5P(2)) and TORC2 signaling pathways. Here, we demonstrate that Slm1 and Slm2 are also targets of sphingolipid signaling during the heat shock response. We show that upon depletion o...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00461-06

    authors: Daquinag A,Fadri M,Jung SY,Qin J,Kunz J

    更新日期:2007-01-01 00:00:00

  • Rpd3- and spt16-mediated nucleosome assembly and transcriptional regulation on yeast ribosomal DNA genes.

    abstract::Ribosomal DNA (rDNA) genes in eukaryotes are organized into multicopy tandem arrays and transcribed by RNA polymerase I. During cell proliferation, ∼50% of these genes are active and have a relatively open chromatin structure characterized by elevated accessibility to psoralen cross-linking. In Saccharomyces cerevisia...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00112-13

    authors: Johnson JM,French SL,Osheim YN,Li M,Hall L,Beyer AL,Smith JS

    更新日期:2013-07-01 00:00:00

  • Stabilization of the E3 ubiquitin ligase Nrdp1 by the deubiquitinating enzyme USP8.

    abstract::Nrdp1 is a RING finger-containing E3 ubiquitin ligase that physically interacts with and regulates steady-state cellular levels of the ErbB3 and ErbB4 receptor tyrosine kinases and has been implicated in the degradation of the inhibitor-of-apoptosis protein BRUCE. Here we demonstrate that the Nrdp1 protein undergoes e...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.24.17.7748-7757.2004

    authors: Wu X,Yen L,Irwin L,Sweeney C,Carraway KL 3rd

    更新日期:2004-09-01 00:00:00

  • CD40 induces apoptosis in carcinoma cells through activation of cytotoxic ligands of the tumor necrosis factor superfamily.

    abstract::CD40, a tumor necrosis factor (TNF) receptor (TNFR) family member, conveys signals regulating diverse cellular responses, ranging from proliferation and differentiation to growth suppression and cell death. The ability of CD40 to mediate apoptosis in carcinoma cells is intriguing given the fact that the CD40 cytoplasm...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.15.5503-5515.2000

    authors: Eliopoulos AG,Davies C,Knox PG,Gallagher NJ,Afford SC,Adams DH,Young LS

    更新日期:2000-08-01 00:00:00

  • The bcl-3 proto-oncogene encodes a nuclear I kappa B-like molecule that preferentially interacts with NF-kappa B p50 and p52 in a phosphorylation-dependent manner.

    abstract::The product of the putative proto-oncogene bcl-3 is an I kappa B-like molecule with novel binding properties specific for a subset of the rel family of transcriptional regulators. In vitro, Bcl-3 protein specifically inhibited the DNA binding of both the homodimeric NF-kappa B p50 subunit and a closely related homolog...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.6.3557

    authors: Nolan GP,Fujita T,Bhatia K,Huppi C,Liou HC,Scott ML,Baltimore D

    更新日期:1993-06-01 00:00:00

  • Triple decoding of hepatitis C virus RNA by programmed translational frameshifting.

    abstract::Ribosomes can be programmed to shift from one reading frame to another during translation. Hepatitis C virus (HCV) uses such a mechanism to produce F protein from the -2/+1 reading frame. We now report that the HCV frameshift signal can mediate the synthesis of the core protein of the zero frame, the F protein of the ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.5.1489-1497.2003

    authors: Choi J,Xu Z,Ou JH

    更新日期:2003-03-01 00:00:00

  • DOUBLETIME plays a noncatalytic role to mediate CLOCK phosphorylation and repress CLOCK-dependent transcription within the Drosophila circadian clock.

    abstract::Circadian clocks keep time via gene expression feedback loops that are controlled by time-of-day-specific changes in the synthesis, activity, and degradation of transcription factors. Within the Drosophila melanogaster circadian clock, DOUBLETIME (DBT) kinase is necessary for the phosphorylation of PERIOD (PER), a tra...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01777-08

    authors: Yu W,Zheng H,Price JL,Hardin PE

    更新日期:2009-03-01 00:00:00

  • Fal1p is an essential DEAD-box protein involved in 40S-ribosomal-subunit biogenesis in Saccharomyces cerevisiae.

    abstract::A previously uncharacterized Saccharomyces cerevisiae gene, FAL1, was found by sequence comparison as a homolog of the eukaryotic translation initiation factor 4A (eIF4A). Fal1p has 55% identity and 73% similarity on the amino acid level to yeast eIF4A, the prototype of ATP-dependent RNA helicases of the DEAD-box prot...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.12.7283

    authors: Kressler D,de la Cruz J,Rojo M,Linder P

    更新日期:1997-12-01 00:00:00

  • Self-association of the Gal4 inhibitor protein Gal80 is impaired by Gal3: evidence for a new mechanism in the GAL gene switch.

    abstract::The DNA-binding transcriptional activator Gal4 and its regulators Gal80 and Gal3 constitute a galactose-responsive switch for the GAL genes of Saccharomyces cerevisiae. Gal4 binds to GAL gene UASGAL (upstream activation sequence in GAL gene promoter) sites as a dimer via its N-terminal domain and activates transcripti...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00646-12

    authors: Egriboz O,Goswami S,Tao X,Dotts K,Schaeffer C,Pilauri V,Hopper JE

    更新日期:2013-09-01 00:00:00

  • Sequence organization and RNA structural motifs directing the mouse primary rRNA-processing event.

    abstract::The first processing step in the maturation of mouse precursor rRNA involves cleavage at nucleotide ca. +650, at the 5' border of a 200-nucleotide region that is conserved across mammals and contains the sequences that direct the processing. To identify the relevant sequence elements, we used rRNAs with small internal...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.1.458

    authors: Craig N,Kass S,Sollner-Webb B

    更新日期:1991-01-01 00:00:00

  • A Swiss 3T3 variant cell line resistant to the effects of tumor promoters cannot be transformed by src.

    abstract::To study the relationship between oncogenesis by v-src and normal cellular signalling pathways, we determined the effects of v-src on 3T3-TNR9 cells, a Swiss 3T3 variant which does not respond mitogenically to tumor promoters such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA). We found that src was unable to transfor...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.8.4155

    authors: Nori M,Shawver LK,Weber MJ

    更新日期:1990-08-01 00:00:00