Occludin S471 Phosphorylation Contributes to Epithelial Monolayer Maturation.

Abstract:

:Multiple organ systems require epithelial barriers for normal function, and barrier loss is a hallmark of diseases ranging from inflammation to epithelial cancers. However, the molecular processes regulating epithelial barrier maturation are not fully elucidated. After contact, epithelial cells undergo size-reductive proliferation and differentiate, creating a dense, highly ordered monolayer with high resistance barriers. We provide evidence that the tight junction protein occludin contributes to the regulation of epithelial cell maturation upon phosphorylation of S471 in its coiled-coil domain. Overexpression of a phosphoinhibitory occludin S471A mutant prevents size-reductive proliferation and subsequent tight junction maturation in a dominant manner. Inhibition of cell proliferation in cell-contacted but immature monolayers recapitulated this phenotype. A kinase screen identified G-protein-coupled receptor kinases (GRKs) targeting S471, and GRK inhibitors delayed epithelial packing and junction maturation. We conclude that occludin contributes to the regulation of size-reductive proliferation and epithelial cell maturation in a phosphorylation-dependent manner.

journal_name

Mol Cell Biol

authors

Bolinger MT,Ramshekar A,Waldschmidt HV,Larsen SD,Bewley MC,Flanagan JM,Antonetti DA

doi

10.1128/MCB.00053-16

subject

Has Abstract

pub_date

2016-07-14 00:00:00

pages

2051-66

issue

15

eissn

0270-7306

issn

1098-5549

pii

MCB.00053-16

journal_volume

36

pub_type

杂志文章
  • Developmental regulation of specific protein interactions with an enhancerlike binding site far upstream from the avian very-low-density apolipoprotein II gene.

    abstract::Expression of the avian very-low-density apolipoprotein II (apoVLDLII) gene is completely dependent on estrogen and restricted to the liver. We have identified binding sites for nonhistone nuclear proteins located between -1.96 and -2.61 kilobases. One of these sites, located at -2.6 kilobases (designated site 1), was...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.1.154

    authors: Hoodless PA,Roy RN,Ryan AK,Haché RJ,Vasa MZ,Deeley RG

    更新日期:1990-01-01 00:00:00

  • H5 gene specific trans-activation by nuclear extracts from avian erythroid cells.

    abstract::Nuclear extracts from chicken erythroid cells selectively stimulate transcription of the chicken histone H5 gene (and not of other chicken histone genes) after coinjection into frog oocytes. This effect is shown to involve an enhancerlike activity, and a region of the H5 gene sufficient to mediate trans-activation is ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.10.3853

    authors: Wigley PL,Wells JR

    更新日期:1987-10-01 00:00:00

  • Identification of an upstream activating sequence and an upstream repressible sequence of the pyruvate kinase gene of the yeast Saccharomyces cerevisiae.

    abstract::To clarify carbon source-dependent control of the glycolytic pathway in the yeast Saccharomyces cerevisiae, we have initiated a study of transcriptional regulation of the pyruvate kinase gene (PYK). By deletion analysis of the 5'-noncoding region of the PYK gene, we have identified an upstream activating sequence (UAS...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.2.442

    authors: Nishizawa M,Araki R,Teranishi Y

    更新日期:1989-02-01 00:00:00

  • Identification of proteins associating with glycosylphosphatidylinositol- anchored T-cadherin on the surface of vascular endothelial cells: role for Grp78/BiP in T-cadherin-dependent cell survival.

    abstract::There is scant knowledge regarding how cell surface lipid-anchored T-cadherin (T-cad) transmits signals through the plasma membrane to its intracellular targets. This study aimed to identify membrane proteins colocalizing with atypical glycosylphosphatidylinositol (GPI)-anchored T-cad on the surface of endothelial cel...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00157-08

    authors: Philippova M,Ivanov D,Joshi MB,Kyriakakis E,Rupp K,Afonyushkin T,Bochkov V,Erne P,Resink TJ

    更新日期:2008-06-01 00:00:00

  • Induced change in a non-mendelian determinant by transplantation of macronucleoplasm in Paramecium tetraurelia.

    abstract::Mutant strain d48 of Paramecium tetraurelia lacks the gene for antigen A in the macronucleus, whereas this gene is present in the micronucleus. Transfer of macronucleoplasm from the wild type to strain d48 caused d48 to revert to the wild type after autogamy. Transfer of cytoplasm was not as effective as transfer of m...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.10.3498

    authors: Harumoto T

    更新日期:1986-10-01 00:00:00

  • MdmX promotes bipolar mitosis to suppress transformation and tumorigenesis in p53-deficient cells and mice.

    abstract::Mdm2 and MdmX are structurally related p53-binding proteins that function as critical negative regulators of p53 activity in embryonic and adult tissue. The overexpression of Mdm2 or MdmX inhibits p53 tumor suppressor functions in vitro, and the amplification of Mdm2 or MdmX is observed in human cancers retaining wild...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01108-07

    authors: Matijasevic Z,Steinman HA,Hoover K,Jones SN

    更新日期:2008-02-01 00:00:00

  • Hypomorphic mutation of the TALE gene Prep1 (pKnox1) causes a major reduction of Pbx and Meis proteins and a pleiotropic embryonic phenotype.

    abstract::The interaction of Prep1 and Pbx homeodomain transcription factors regulates their activity, nuclear localization, and likely, function in development. To understand the in vivo role of Prep1, we have analyzed an embryonic lethal hypomorphic mutant mouse (Prep1(i/i)). Prep1(i/i) embryos die at embryonic day 17.5 (E17....

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00313-06

    authors: Ferretti E,Villaescusa JC,Di Rosa P,Fernandez-Diaz LC,Longobardi E,Mazzieri R,Miccio A,Micali N,Selleri L,Ferrari G,Blasi F

    更新日期:2006-08-01 00:00:00

  • Evidence for an overlapping role of CLOCK and NPAS2 transcription factors in liver circadian oscillators.

    abstract::The mechanisms underlying the circadian control of gene expression in peripheral tissues and influencing many biological pathways are poorly defined. Factor VII (FVII), the protease triggering blood coagulation, represents a valuable model to address this issue in liver since its plasma levels oscillate in a circadian...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01931-07

    authors: Bertolucci C,Cavallari N,Colognesi I,Aguzzi J,Chen Z,Caruso P,Foá A,Tosini G,Bernardi F,Pinotti M

    更新日期:2008-05-01 00:00:00

  • Structure of the bovine tau gene: alternatively spliced transcripts generate a protein family.

    abstract::Tau, a major class of microtubule-associated proteins, consists of a family of proteins that are heterogeneous in molecular weight. The presence of internal deletions in previously described cDNA clones for murine and bovine tau suggested that alternative splicing of transcripts could account for the protein size hete...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.4.1389

    authors: Himmler A

    更新日期:1989-04-01 00:00:00

  • A p21-ZEB1 complex inhibits epithelial-mesenchymal transition through the microRNA 183-96-182 cluster.

    abstract::The tumor suppressor p21 acts as a cell cycle inhibitor and has also been shown to regulate gene expression by functioning as a transcription corepressor. Here, we identified p21-regulated microRNAs (miRNAs) by sequencing small RNAs from isogenic p21(+/+) and p21(-/-) cells. Three abundant miRNA clusters, miR-200b-200...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01043-13

    authors: Li XL,Hara T,Choi Y,Subramanian M,Francis P,Bilke S,Walker RL,Pineda M,Zhu Y,Yang Y,Luo J,Wakefield LM,Brabletz T,Park BH,Sharma S,Chowdhury D,Meltzer PS,Lal A

    更新日期:2014-02-01 00:00:00

  • The SET2-RPB1 interaction domain of human RECQ5 is important for transcription-associated genome stability.

    abstract::The conserved RECQ5 DNA helicase is a tumor suppressor in mammalian cells. Defects in RECQ5 lead to the accumulation of spontaneous DNA double-stranded breaks (DSBs) during replication, despite the fact that these cells are proficient in DSB repair by homologous recombination (HR). The reason for this is unknown. Here...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01137-10

    authors: Li M,Xu X,Liu Y

    更新日期:2011-05-01 00:00:00

  • Commitment and effector phases of the physiological cell death pathway elucidated with respect to Bcl-2 caspase, and cyclin-dependent kinase activities.

    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

    authors: Harvey KJ,Blomquist JF,Ucker DS

    更新日期:1998-05-01 00:00:00

  • Downregulation of CIITA function by protein kinase a (PKA)-mediated phosphorylation: mechanism of prostaglandin E, cyclic AMP, and PKA inhibition of class II major histocompatibility complex expression in monocytic lines.

    abstract::Prostaglandins, pleiotropic immune modulators that induce protein kinase A (PKA), inhibit gamma interferon induction of class II major histocompatibility complex (MHC) genes. We show that phosphorylation of CIITA by PKA accounts for this inhibition. Treatment with prostaglandin E or 8-bromo-cyclic AMP or transfection ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.14.4626-4635.2001

    authors: Li G,Harton JA,Zhu X,Ting JP

    更新日期:2001-07-01 00:00:00

  • Insulin receptor substrates Irs1 and Irs2 coordinate skeletal muscle growth and metabolism via the Akt and AMPK pathways.

    abstract::Coordination of skeletal muscle growth and metabolism with nutrient availability is critical for metabolic homeostasis. To establish the role of insulin-like signaling in this process, we used muscle creatine kinase (MCK)-Cre to disrupt expression of insulin receptor substrates Irs1 and Irs2 in mouse skeletal/cardiac ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00983-10

    authors: Long YC,Cheng Z,Copps KD,White MF

    更新日期:2011-02-01 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

  • UV radiation facilitates methotrexate resistance and amplification of the dihydrofolate reductase gene in cultured 3T6 mouse cells.

    abstract::Pretreatment of 3T6 murine cells with the carcinogen UV radiation or N-acetoxy-N-acetylaminofluorene increased the number of methotrexate-resistant colonies. This carcinogen-induced enhancement was seen only at low toxicities. The enhancement was transient and was observed at its maximum when cells were subjected to m...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.4.6.1050

    authors: Tlsty TD,Brown PC,Schimke RT

    更新日期:1984-06-01 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

  • 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

  • The Myc negative autoregulation mechanism requires Myc-Max association and involves the c-myc P2 minimal promoter.

    abstract::Increasing evidence supports an important biological role for Myc in the downregulation of specific gene transcription. Recent studies suggest that c-Myc may suppress promoter activity through proteins of the basal transcription machinery. We have previously reported that Myc protein, in combination with additional ce...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.1.100

    authors: Facchini LM,Chen S,Marhin WW,Lear JN,Penn LZ

    更新日期:1997-01-01 00:00:00

  • Cleavage of a hydrophilic C-terminal domain increases growth-inhibitory activity of oncostatin M.

    abstract::Oncostatin M is a polypeptide cytokine, produced by normal and malignant hematopoietic cells, that has several in vitro activities, including the ability to inhibit growth of cultured carcinoma cells. Here we present a structural and functional comparison of two oncostatin M-related proteins (Mr 36,000 and 32,000) sec...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.5.1882

    authors: Linsley PS,Kallestad J,Ochs V,Neubauer M

    更新日期:1990-05-01 00:00:00

  • Trm112 is required for Bud23-mediated methylation of the 18S rRNA at position G1575.

    abstract::Posttranscriptional and posttranslational modification of macromolecules is known to fine-tune their functions. Trm112 is unique, acting as an activator of both tRNA and protein methyltransferases. Here we report that in Saccharomyces cerevisiae, Trm112 is required for efficient ribosome synthesis and progression thro...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.06623-11

    authors: Figaro S,Wacheul L,Schillewaert S,Graille M,Huvelle E,Mongeard R,Zorbas C,Lafontaine DL,Heurgué-Hamard V

    更新日期:2012-06-01 00:00:00

  • Mice lacking paternally expressed Pref-1/Dlk1 display growth retardation and accelerated adiposity.

    abstract::Preadipocyte factor 1 (Pref-1/Dlk1) inhibits in vitro adipocyte differentiation and has been recently reported to be a paternally expressed imprinted gene at human chromosome 14q32. Studies on human chromosome 14 deletions and maternal uniparental disomy (mUPD) 14 suggest that misexpression of a yet-to-be-identified i...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.15.5585-5592.2002

    authors: Moon YS,Smas CM,Lee K,Villena JA,Kim KH,Yun EJ,Sul HS

    更新日期:2002-08-01 00:00:00

  • REF2 encodes an RNA-binding protein directly involved in yeast mRNA 3'-end formation.

    abstract::The Saccharomyces cerevisiae mutant ref2-1 (REF = RNA end formation) was originally identified by a genetic strategy predicted to detect decreases in the use of a CYC1 poly(A) site interposed within the intron of an ACT1-HIS4 fusion reporter gene. Direct RNA analysis now proves this effect and also demonstrates the tr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.3.1689

    authors: Russnak R,Nehrke KW,Platt T

    更新日期:1995-03-01 00:00:00

  • Positive and negative modulation of Jun action by thyroid hormone receptor at a unique AP1 site.

    abstract::We have characterized the putative AP1 site in the backbone of pUC plasmids and found unique regulatory effects. The site, which mapped to a 19-bp region around nucleotide 37, conferred transcriptional activation by Jun or Jun/Fos that was boosted up to fivefold by unliganded thyroid hormone receptor (TR). Thyroid hor...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.5.3042

    authors: Lopez G,Schaufele F,Webb P,Holloway JM,Baxter JD,Kushner PJ

    更新日期:1993-05-01 00:00:00

  • Transcription of the HS2 enhancer toward a cis-linked gene is independent of the orientation, position, and distance of the enhancer relative to the gene.

    abstract::The locus control region (LCR) regulates transcription of the downstream beta-like globin genes 10 to 50 kb away. Among hypersensitive sites HS4, -3, -2, and -1, which define the LCR in erythroid cells, HS2 possesses prominent enhancer function. The mechanism by which the HS2 enhancer and other functional components o...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.7.3955

    authors: Kong S,Bohl D,Li C,Tuan D

    更新日期:1997-07-01 00:00:00

  • Expression of the src and abl cellular oncogenes during development of Drosophila melanogaster.

    abstract::Transcription of the Drosophila homologs of the abl and src cellular oncogenes, termed Dash and Dsrc , respectively, was studied. Despite the fact that Dash and Dsrc share sequence homology, they have distinct patterns of transcription during development. The Dash transcript, 6.2 kilobases long, is found in maternal R...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.4.5.982

    authors: Lev Z,Leibovitz N,Segev O,Shilo BZ

    更新日期:1984-05-01 00:00:00

  • Mutational analysis of the DNA binding, dimerization, and transcriptional activation domains of MEF2C.

    abstract::There are four members of the myocyte enhancer factor 2 (MEF2) family of transcription factors in vertebrates, MEF2A, -B, -C, and -D, which have homology within a MADS box at their amino termini and an adjacent motif known as the MEF2 domain. These factors activate muscle gene expression by binding as homo- and hetero...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.6.2627

    authors: Molkentin JD,Black BL,Martin JF,Olson EN

    更新日期:1996-06-01 00:00:00

  • Mammalian DET1 regulates Cul4A activity and forms stable complexes with E2 ubiquitin-conjugating enzymes.

    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

    authors: Pick E,Lau OS,Tsuge T,Menon S,Tong Y,Dohmae N,Plafker SM,Deng XW,Wei N

    更新日期:2007-07-01 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

  • 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