当前位置： SCI文献检索 > MOLECULAR AND CELLULAR BIOLOGY期刊下所有文献 > Conditional knockout mice reveal an essential role of protein phosphatase 4 in thymocyte development and pre-T-cell receptor signaling.

Conditional knockout mice reveal an essential role of protein phosphatase 4 in thymocyte development and pre-T-cell receptor signaling.

Abstract：

:Okadaic acid-sensitive serine/threonine phosphatases have been shown to regulate interleukin-2 transcription and T-cell activation. Okadaic acid inhibits protein phosphatase 4 (PP4), a novel PP2A-related serine/threonine phosphatase, at a 50% inhibitory concentration (IC(50)) comparable to that for PP2A. This raises the possibility that some cellular functions of PP2A, determined in T cells by using okadaic acid, may in fact be those of PP4. To investigate the in vivo roles of PP4 in T cells, we generated conventional and T-cell-specific PP4 conditional knockout mice. We found that the ablation of PP4 led to the embryonic lethality of mice. PP4 gene deletion in the T-cell lineage resulted in aberrant thymocyte development, including T-cell arrest at the double-negative 3 stage (CD4(-) CD8(-) CD25(+) CD44(-)), abnormal thymocyte maturation, and lower efficacy of positive selection. PP4-deficient thymocytes showed decreased proliferation and enhanced apoptosis in vivo. Analysis of pre-T-cell receptor (pre-TCR) signaling further revealed impaired calcium flux and phospholipase C-gamma1-extracellular signal-regulated kinase activation in the absence of PP4. Anti-CD3 injection in PP4-deficient mice led to enhanced thymocyte apoptosis, accompanied by increased proapoptotic Bim but decreased antiapoptotic Bcl-xL protein levels. In the periphery, antigen-specific T-cell proliferation and T-cell-mediated immune responses in PP4-deficient mice were dramatically compromised. Thus, our results indicate that PP4 is essential for thymocyte development and pre-TCR signaling.

journal_name

Mol Cell Biol

journal_title

Molecular and cellular biology

authors

Shui JW,Hu MC,Tan TH

doi

10.1128/MCB.00799-06

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

79-91

issue

1

eissn

0270-7306

issn

1098-5549

pii

MCB.00799-06

journal_volume

27

pub_type

杂志文章

相关文献

MOLECULAR AND CELLULAR BIOLOGY文献大全
  • Canonical Notch signaling is dispensable for early cell fate specifications in mammals.

    abstract：:The canonical Notch signaling pathway mediated by Delta- and Jagged-like Notch ligands determines a variety of cell fates in metazoa. In Caenorhabditis elegans and sea urchins, canonical Notch signaling is essential for different cell fate specifications during early embryogenesis or the formation of endoderm, mesoder...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.25.21.9503-9508.2005

    authors： Shi S,Stahl M,Lu L,Stanley P

    更新日期：2005-11-01 00:00:00

  • LZTS2 is a novel beta-catenin-interacting protein and regulates the nuclear export of beta-catenin.

    abstract：:Beta-catenin plays multiple roles in cell-cell adhesion and Wnt signal transduction. Through the Wnt signal, the cellular level of beta-catenin is constitutively regulated by the multicomponent destruction complex containing glycogen synthase kinase 3beta, axin, and adenomatous polyposis coli. Here, we present multipl...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.01031-06

    authors： Thyssen G,Li TH,Lehmann L,Zhuo M,Sharma M,Sun Z

    更新日期：2006-12-01 00:00:00

  • HOXA9 participates in the transcriptional activation of E-selectin in endothelial cells.

    abstract：:The homeobox gene HOXA9 has recently been shown to be an important regulator of endothelial cell (EC) differentiation and activation in addition to its role in embryonic development and hematopoiesis. In this report, we have determined that the EC-leukocyte adhesion molecule E-selectin is a key target for HOXA9. The d...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.00052-07

    authors： Bandyopadhyay S,Ashraf MZ,Daher P,Howe PH,DiCorleto PE

    更新日期：2007-06-01 00:00:00

  • E2F3 loss has opposing effects on different pRB-deficient tumors, resulting in suppression of pituitary tumors but metastasis of medullary thyroid carcinomas.

    abstract：:The E2F transcription factors are key downstream targets of the retinoblastoma protein (pRB) tumor suppressor. We have previously shown that E2F3 plays a critical role in mediating the mitogen-induced activation of E2F-responsive genes and contributes to both the inappropriate proliferation and the p53-dependent apopt...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.23.18.6542-6552.2003

    authors： Ziebold U,Lee EY,Bronson RT,Lees JA

    更新日期：2003-09-01 00:00:00

  • Intramolecular regulation of phospholipase C-gamma1 by its C-terminal Src homology 2 domain.

    abstract：:Phosphoinositide-specific phospholipase C-gamma1 (PLC-gamma1) is a key enzyme that governs cellular functions such as gene transcription, secretion, proliferation, motility, and development. Here, we show that PLC-gamma1 is regulated via a novel autoinhibitory mechanism involving its carboxy-terminal Src homology (SH2...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.01400-06

    authors： DeBell K,Graham L,Reischl I,Serrano C,Bonvini E,Rellahan B

    更新日期：2007-02-01 00:00:00

  • Studies of partially transforming polyomavirus mutants establish a role for phosphatidylinositol 3-kinase in activation of pp70 S6 kinase.

    abstract：:Infection of mouse fibroblasts by wild-type polyomavirus results in increased phosphorylation of ribosomal protein S6 (D.A. Talmage, J. Blenis, and T.L. Benjamin, Mol. Cell. Biol. 8:2309-2315, 1988). Here we identify pp70 S6 kinase (pp70S6K) as a target for signal transduction events leading from polyomavirus middle t...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.16.6.2728

    authors： Dahl J,Freund R,Blenis J,Benjamin TL

    更新日期：1996-06-01 00:00:00

  • Raf kinase inhibitory protein function is regulated via a flexible pocket and novel phosphorylation-dependent mechanism.

    abstract：:Raf kinase inhibitory protein (RKIP/PEBP1), a member of the phosphatidylethanolamine binding protein family that possesses a conserved ligand-binding pocket, negatively regulates the mammalian mitogen-activated protein kinase (MAPK) signaling cascade. Mutation of a conserved site (P74L) within the pocket leads to a lo...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.01271-08

    authors： Granovsky AE,Clark MC,McElheny D,Heil G,Hong J,Liu X,Kim Y,Joachimiak G,Joachimiak A,Koide S,Rosner MR

    更新日期：2009-03-01 00:00:00

  • Progesterone and glucocorticoid receptors recruit distinct coactivator complexes and promote distinct patterns of local chromatin modification.

    abstract：:It is well established that steroid receptor function requires interaction with coactivators. However, the mechanisms through which steroid receptors elicit precise assembly of coactivator complexes and the way the steroid activation signal is transduced remain elusive. Using a T47D cell line stably integrated with a ...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.23.11.3763-3773.2003

    authors： Li X,Wong J,Tsai SY,Tsai MJ,O'Malley BW

    更新日期：2003-06-01 00:00:00

  • Loss of chloroplast DNA methylation during dedifferentiation of Chlamydomonas reinhardi gametes.

    abstract：:In Chlamydomonas reinhardi the chloroplast DNA (ch;DNA) of mating type plus cells undergoes cyclical methylation and demethylation during the life cycle. Methylation occurs during gametogenesis, and fully differentiated gametes can be dedifferentiated back to vegetative cells which contain nonmethylated chlDNA by the ...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.4.10.2103

    authors： Sano H,Grabowy C,Sager R

    更新日期：1984-10-01 00:00:00

  • Characterization of BCE-1, a transcriptional enhancer regulated by prolactin and extracellular matrix and modulated by the state of histone acetylation.

    abstract：:We have previously described a 160-bp enhancer (BCE-1) in the bovine beta-casein gene that is activated in the presence of prolactin and extracellular matrix (ECM). Here we report the characterization of the enhancer by deletion and site-directed mutagenesis, electrophoretic mobility shift analysis, and in vivo footpr...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.18.4.2184

    authors： Myers CA,Schmidhauser C,Mellentin-Michelotti J,Fragoso G,Roskelley CD,Casperson G,Mossi R,Pujuguet P,Hager G,Bissell MJ

    更新日期：1998-04-01 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

  • The general transcription factors IIA, IIB, IIF, and IIE are required for RNA polymerase II transcription from the human U1 small nuclear RNA promoter.

    abstract：:RNA polymerase II transcribes the mRNA-encoding genes and the majority of the small nuclear RNA (snRNA) genes. The formation of a minimal functional transcription initiation complex on a TATA-box-containing mRNA promoter has been well characterized and involves the ordered assembly of a number of general transcription...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.19.3.2130

    authors： Kuhlman TC,Cho H,Reinberg D,Hernandez N

    更新日期：1999-03-01 00:00:00

  • Tumor necrosis factor-related apoptosis-inducing ligand induces caspase-dependent interleukin-8 expression and apoptosis in human astroglioma cells.

    abstract：:Among the tumor necrosis factor (TNF) family of cytokines, FasL and TNF-related apoptosis-inducing ligand (TRAIL) are known to induce cell death via caspase activation. Recently, other biological functions of these death ligands have been postulated in vitro and in vivo. It was previously shown that Fas ligation induc...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.22.3.724-736.2002

    authors： Choi C,Kutsch O,Park J,Zhou T,Seol DW,Benveniste EN

    更新日期：2002-02-01 00:00:00

  • Heat shock transcription factor Hsf1 is involved in tumor progression via regulation of hypoxia-inducible factor 1 and RNA-binding protein HuR.

    abstract：:Previously we demonstrated that the heat shock transcription factor Hsf1 is indispensable for transformation of mammary epithelial cells by the Her2 oncogene. Since Hsf1 affects oncogene-induced senescence (OIS), these findings suggest that Hsf1 affects tumor initiation when OIS plays a role. Indeed, here we report th...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.05921-11

    authors： Gabai VL,Meng L,Kim G,Mills TA,Benjamin IJ,Sherman MY

    更新日期：2012-03-01 00:00:00

  • Mutations in the yeast KEX2 gene cause a Vma(-)-like phenotype: a possible role for the Kex2 endoprotease in vacuolar acidification.

    abstract：:Mutants of Saccharomyces cerevisiae that lack vacuolar proton-translocating ATPase (V-ATPase) activity show a well-defined set of Vma- (stands for vacuolar membrane ATPase activity) phenotypes that include pH-conditional growth, increased calcium sensitivity, and the inability to grow on nonfermentable carbon sources....

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.18.3.1534

    authors： Oluwatosin YE,Kane PM

    更新日期：1998-03-01 00:00:00

  • Transcription from the polyoma late promoter in cells stably transformed by chimeric plasmids.

    abstract：:We have examined the expression of chimeric plasmids containing coding sequences for the herpes simplex virus thymidine kinase (tk) gene or the Tn5 gene for neomycin resistance (neo) linked to the late promoter of polyoma DNA. Although polyoma late genes are generally not expressed in transformed cells containing only...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.5.4.797

    authors： Kern FG,Basilico C

    更新日期：1985-04-01 00:00:00

  • A microRNA signature of hypoxia.

    abstract：:Recent research has identified critical roles for microRNAs in a large number of cellular processes, including tumorigenic transformation. While significant progress has been made towards understanding the mechanisms of gene regulation by microRNAs, much less is known about factors affecting the expression of these no...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.01395-06

    authors： Kulshreshtha R,Ferracin M,Wojcik SE,Garzon R,Alder H,Agosto-Perez FJ,Davuluri R,Liu CG,Croce CM,Negrini M,Calin GA,Ivan M

    更新日期：2007-03-01 00:00:00

  • RNA polymerase II accumulation in the promoter-proximal region of the dihydrofolate reductase and gamma-actin genes.

    abstract：:The carboxyl-terminal domain (CTD) of RNA polymerase II (Pol II) can be phosphorylated at serine 2 (Ser-2) and serine 5 (Ser-5) of the CTD heptad repeat YSPTSPS, and this phosphorylation is important in coupling transcription to RNA processing, including 5' capping, splicing, and polyadenylation. The mammalian endogen...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.23.6.1961-1967.2003

    authors： Cheng C,Sharp PA

    更新日期：2003-03-01 00:00:00

  • Interactions of the yeast SF3b splicing factor.

    abstract：:The U2 snRNP promotes prespliceosome assembly through interactions that minimally involve the branchpoint binding protein, Mud2p, and the pre-mRNA. We previously showed that seven proteins copurify with the yeast (Saccharomyces cerevisiae) SF3b U2 subcomplex that associates with the pre-mRNA branchpoint region: Rse1p,...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.25.24.10745-10754.2005

    authors： Wang Q,He J,Lynn B,Rymond BC

    更新日期：2005-12-01 00:00:00

  • ZFP100, a component of the active U7 snRNP limiting for histone pre-mRNA processing, is required for entry into S phase.

    abstract：:Metazoan replication-dependent histone mRNAs are the only eukaryotic mRNAs that are not polyadenylated. The cleavage of histone pre-mRNA to form the unique 3' end requires the U7 snRNP and the stem-loop binding protein (SLBP) that binds the 3' end of histone mRNA. U7 snRNP contains three novel proteins, Lsm10 and Lsm1...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.00391-06

    authors： Wagner EJ,Marzluff WF

    更新日期：2006-09-01 00:00:00

  • Expression of the three human major histocompatibility complex class II isotypes exhibits a differential dependence on the transcription factor RFXAP.

    abstract：:Major histocompatibility complex class II (MHCII) molecules play a pivotal role in the immune system because they direct the development and activation of CD4(+) T cells. There are three human MHCII isotypes, HLA-DR, HLA-DQ, and HLA-DP. Key transcription factors controlling MHCII genes have been identified by virtue o...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.21.17.5699-5709.2001

    authors： Peretti M,Villard J,Barras E,Zufferey M,Reith W

    更新日期：2001-09-01 00:00:00

  • Many transcribed regions of the Onchocerca volvulus genome contain the spliced leader sequence of Caenorhabditis elegans.

    abstract：:Genomic DNAs of the related parasitic nematodes Onchocerca volvulus and Dirofilariae immitis, and a cDNA library of O. volvulus, were examined for the presence of the 22-nucleotide spliced leader (SL) found at the 5' ends of 10 to 15% of the mRNAs in the free-living nematode Caenorhabditis elegans. As in C. elegans, g...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.10.6.2765

    authors： Zeng WL,Alarcon CM,Donelson JE

    更新日期：1990-06-01 00:00:00

  • The emerging role of HP1 in the DNA damage response.

    abstract：:Heterochromatin protein 1 (HP1) family members are versatile proteins involved in transcription, chromatin organization, and replication. Recent findings now have implicated HP1 proteins in the DNA damage response as well. Cell-biological approaches showed that reducing the levels of all three HP1 isoforms enhances DN...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章,评审

    doi：10.1128/MCB.01048-09

    authors： Dinant C,Luijsterburg MS

    更新日期：2009-12-01 00:00:00

  • Significance of C-terminal cysteine modifications to the biological activity of the Saccharomyces cerevisiae a-factor mating pheromone.

    abstract：:We have undertaken total synthesis of the Saccharomyces cerevisiae a-factor (NH2-YIIKGVFWDPAC[S-farnesyl]-COOCH3) and several Cys-12 analogs to determine the significance of S-farnesylation and carboxy-terminal methyl esterification to the biological activity of this lipopeptide mating pheromone. Replacement of either...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.11.7.3603

    authors： Marcus S,Caldwell GA,Miller D,Xue CB,Naider F,Becker JM

    更新日期：1991-07-01 00:00:00

  • TFIIA induces conformational changes in TFIID via interactions with the basic repeat.

    abstract：:DNA-binding studies with Saccharomyces cerevisiae TFIID point mutants indicated that TFIIA interacts with the basic repeat region of TFIID and induces structural changes. The latter was shown by the ability of TFIIA to compensate for TFIID point mutants defective for DNA binding. Interaction with TFIIA also rendered T...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.12.11.5189

    authors： Lee DK,DeJong J,Hashimoto S,Horikoshi M,Roeder RG

    更新日期：1992-11-01 00:00:00

  • B-myc inhibits neoplastic transformation and transcriptional activation by c-myc.

    abstract：:B-myc is a recently described myc gene whose product has not been functionally characterized. The predicted product of B-myc is a 168-amino-acid protein with extensive homology to the c-Myc amino-terminal region, previously shown to contain a transcriptional activation domain. We hypothesized that B-Myc might also fun...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.13.2.1130

    authors： Resar LM,Dolde C,Barrett JF,Dang CV

    更新日期：1993-02-01 00:00:00

  • ARS2 is a conserved eukaryotic gene essential for early mammalian development.

    abstract：:Determining the functions of novel genes implicated in cell survival is directly relevant to our understanding of mammalian development and carcinogenesis. ARS2 is an evolutionarily conserved gene that confers arsenite resistance on arsenite-sensitive Chinese hamster ovary cells. Little is known regarding the function...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.01565-07

    authors： Wilson MD,Wang D,Wagner R,Breyssens H,Gertsenstein M,Lobe C,Lu X,Nagy A,Burke RD,Koop BF,Howard PL

    更新日期：2008-03-01 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

  • Transcriptional activity of neural retina leucine zipper (Nrl) is regulated by c-Jun N-terminal kinase and Tip60 during retina development.

    abstract：:Neural retina leucine zipper (Nrl), a key basic motif leucine zipper (bZIP) transcription factor, modulates rod photoreceptor differentiation by activating rod-specific target genes. In searching for factors that might couple with Nrl to modulate its transcriptional activity through posttranslational modification, we ...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.06440-11

    authors： Kim JW,Jang SM,Kim CH,An JH,Choi KH

    更新日期：2012-05-01 00:00:00

  • Age-related macular degeneration-associated silent polymorphisms in HtrA1 impair its ability to antagonize insulin-like growth factor 1.

    abstract：:Synonymous single nucleotide polymorphisms (SNPs) within a transcript's coding region produce no change in the amino acid sequence of the protein product and are therefore intuitively assumed to have a neutral effect on protein function. We report that two common variants of high-temperature requirement A1 (HTRA1) tha...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.01283-12

    authors： Jacobo SM,Deangelis MM,Kim IK,Kazlauskas A

    更新日期：2013-05-01 00:00:00