Apolipoprotein(a) stimulates nuclear translocation of β-catenin: a novel pathogenic mechanism for lipoprotein(a).

Abstract:

:Lipoprotein(a) (Lp(a)) is associated with cardiovascular disease risk. This may be attributable to the ability of Lp(a) to elicit endothelial dysfunction. We previously reported that apolipoprotein(a) (apo(a); the distinguishing kringle-containing component of Lp(a)) elicits cytoskeletal rearrangements in vascular endothelial cells, resulting in increased cellular permeability. These effects require a strong lysine-binding site (LBS) in apo(a). We now report that apo(a) induces both nuclear β-catenin-mediated cyclooxygenase-2 (COX-2) expression and prostaglandin E2 secretion, indicating a proinflammatory role for Lp(a). Apo(a) caused the disruption of VE-cadherin/β-catenin complexes in a Src-dependent manner, decreased β-catenin phosphorylation, and increased phosphorylation of Akt and glycogen synthase kinase-3β, ultimately resulting in increased nuclear translocation of β-catenin; all of these effects are downstream of apo(a) attenuation of phosphatase and tensin homologue deleted on chromosome 10 activity. The β-catenin-mediated effects of apo(a) on COX-2 expression were absent using a mutant apo(a) lacking the strong LBS. Of interest, the normal and LBS mutant forms of apo(a) bound to human umbilical vein endothelial cells in a similar manner, and the binding of neither was affected by lysine analogues. Taken together, our findings suggest a novel mechanism by which apo(a) can induce proinflammatory and proatherosclerotic effects through modulation of vascular endothelial cell function.

journal_name

Mol Biol Cell

authors

Cho T,Romagnuolo R,Scipione C,Boffa MB,Koschinsky ML

doi

10.1091/mbc.E12-08-0637

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

210-21

issue

3

eissn

1059-1524

issn

1939-4586

pii

mbc.E12-08-0637

journal_volume

24

pub_type

杂志文章
  • Systematic structure-function analysis of the small GTPase Arf1 in yeast.

    abstract::Members of the ADP-ribosylation factor (Arf) family of small GTPases are implicated in vesicle traffic in the secretory pathway, although their precise function remains unclear. We generated a series of 23 clustered charge-to-alanine mutations in the Arf1 protein of Saccharomyces cerevisiae to determine the portions o...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.02-01-0007

    authors: Click ES,Stearns T,Botstein D

    更新日期:2002-05-01 00:00:00

  • Activation of androgen receptor function by a novel nuclear protein kinase.

    abstract::Androgen receptor (AR) belongs to the nuclear receptor superfamily and mediates the biological actions of male sex steroids. In this work, we have characterized a novel 130-kDa Ser/Thr protein kinase ANPK that interacts with the zinc finger region of AR in vivo and in vitro. The catalytic kinase domain of ANPK shares ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.9.9.2527

    authors: Moilanen AM,Karvonen U,Poukka H,Jänne OA,Palvimo JJ

    更新日期:1998-09-01 00:00:00

  • Src-dependent TrkA transactivation is required for pituitary adenylate cyclase-activating polypeptide 38-mediated Rit activation and neuronal differentiation.

    abstract::Pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent neuropeptide that possesses both neurotrophic and neurodevelopmental effects. Recently, the Rit GTPase was found to be activated by a novel Galpha/cAMP/exchange protein activated by cyclic AMP (Epac)-dependent signaling pathway and required for PAC...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-12-1033

    authors: Shi GX,Jin L,Andres DA

    更新日期:2010-05-01 00:00:00

  • Sequestration of cholesterol within the host late endocytic pathway restricts liver-stage Plasmodium development.

    abstract::While lysosomes are degradative compartments and one of the defenses against invading pathogens, they are also hubs of metabolic activity. Late endocytic compartments accumulate around Plasmodium berghei liver-stage parasites during development, and whether this is a host defense strategy or active recruitment by the ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-07-0531

    authors: Petersen W,Stenzel W,Silvie O,Blanz J,Saftig P,Matuschewski K,Ingmundson A

    更新日期:2017-03-15 00:00:00

  • Characterization of a new gammaTuRC subunit with WD repeats.

    abstract::The gamma-tubulin ring complex (gammaTuRC), consisting of multiple protein subunits, can nucleate microtubule assembly. Although many subunits of the gammaTuRC have been identified, a complete set remains to be defined in any organism. In addition, how the subunits interact with each other to assemble into gammaTuRC r...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-01-0034

    authors: Gunawardane RN,Martin OC,Zheng Y

    更新日期:2003-03-01 00:00:00

  • Postreplication repair and PCNA modification in Schizosaccharomyces pombe.

    abstract::Ubiquitination of proliferating cell nuclear antigen (PCNA) plays a crucial role in regulating replication past DNA damage in eukaryotes, but the detailed mechanisms appear to vary in different organisms. We have examined the modification of PCNA in Schizosaccharomyces pombe. We find that, in response to UV irradiatio...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-11-1008

    authors: Frampton J,Irmisch A,Green CM,Neiss A,Trickey M,Ulrich HD,Furuya K,Watts FZ,Carr AM,Lehmann AR

    更新日期:2006-07-01 00:00:00

  • Drosophila Wee1 kinase rescues fission yeast from mitotic catastrophe and phosphorylates Drosophila Cdc2 in vitro.

    abstract::Cdc2 kinase activity is required for triggering entry into mitosis in all known eukaryotes. Elaborate mechanisms have evolved for regulating Cdc2 activity so that mitosis occurs in a timely manner, when preparations for its execution are complete. In Schizosaccharomyces pombe, Wee1 and a related Mik1 kinase are Cdc2-i...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.6.10.1333

    authors: Campbell SD,Sprenger F,Edgar BA,O'Farrell PH

    更新日期:1995-10-01 00:00:00

  • Mechanically patterned neuromuscular junctions-in-a-dish have improved functional maturation.

    abstract::Motor neuron (MN) diseases are progressive disorders resulting from degeneration of neuromuscular junctions (NMJs), which form the connection between MNs and muscle fibers. NMJ-in-a-dish models have been developed to examine human MN-associated dysfunction with disease; however such coculture models have randomly orie...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E17-01-0046

    authors: Happe CL,Tenerelli KP,Gromova AK,Kolb F,Engler AJ

    更新日期:2017-07-07 00:00:00

  • Reorganization of budding yeast cytoplasm upon energy depletion.

    abstract::Yeast cells, when exposed to stress, can enter a protective state in which cell division, growth, and metabolism are down-regulated. They remain viable in this state until nutrients become available again. How cells enter this protective survival state and what happens at a cellular and subcellular level are largely u...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E20-02-0125

    authors: Marini G,Nüske E,Leng W,Alberti S,Pigino G

    更新日期:2020-06-01 00:00:00

  • Loss of Gα12/13 exacerbates apical area dependence of actomyosin contractility.

    abstract::During development, coordinated cell shape changes alter tissue shape. In the Drosophila ventral furrow and other epithelia, apical constriction of hundreds of epithelial cells folds the tissue. Genes in the Gα12/13 pathway coordinate collective apical constriction, but the mechanism of coordination is poorly understo...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-05-0305

    authors: Xie S,Mason FM,Martin AC

    更新日期:2016-11-07 00:00:00

  • Novel control of S phase of the cell cycle by ubiquitin-conjugating enzyme H7.

    abstract::Timely degradation of regulatory proteins by the ubiquitin proteolytic pathway (UPP) is an established paradigm of cell cycle regulation during the G2/M and G1/S transitions. Less is known about roles for the UPP during S phase. Here we present evidence that dynamic cell cycle-dependent changes in levels of UbcH7 regu...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-01-0036

    authors: Whitcomb EA,Dudek EJ,Liu Q,Taylor A

    更新日期:2009-01-01 00:00:00

  • Caspase-mediated cleavage of p130cas in etoposide-induced apoptotic Rat-1 cells.

    abstract::Apoptosis causes characteristic morphological changes in cells, including membrane blebbing, cell detachment from the extracellular matrix, and loss of cell-cell contacts. We investigated the changes in focal adhesion proteins during etoposide-induced apoptosis in Rat-1 cells and found that during apoptosis, p130cas (...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.3.929

    authors: Kook S,Shim SR,Choi SJ,Ahnn J,Kim JI,Eom SH,Jung YK,Paik SG,Song WK

    更新日期:2000-03-01 00:00:00

  • Magazine or journal--what is the difference? The role of the monitoring editor.

    abstract::Scientific communication, career advancement, and funding decisions are all dependent on research publications. The way manuscripts are handled by high-visibility, professionally edited magazines differs from the way academic journals evaluate manuscripts, using active scientists as monitoring editors. In this essay, ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E12-12-0899

    authors: Bretscher A

    更新日期:2013-04-01 00:00:00

  • Phosphorylation of a conserved integrin alpha 3 QPSXXE motif regulates signaling, motility, and cytoskeletal engagement.

    abstract::Integrin alpha 3A cytoplasmic tail phosphorylation was mapped to amino acid S1042, as determined by mass spectrometry, and confirmed by mutagenesis. This residue occurs within a "QPSXXE" motif conserved in multiple alpha chains (alpha 3A, alpha 6A, alpha 7A), from multiple species. Phosphorylation of alpha 3A and alph...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.2.351

    authors: Zhang XA,Bontrager AL,Stipp CS,Kraeft SK,Bazzoni G,Chen LB,Hemler ME

    更新日期:2001-02-01 00:00:00

  • The interaction and colocalization of Sam68 with the splicing-associated factor YT521-B in nuclear dots is regulated by the Src family kinase p59(fyn).

    abstract::Alternative pre-mRNA splicing patterns can change an extracellular stimulus, but the signaling pathways leading to these changes are still poorly characterized. Here, we describe a tyrosine-phosphorylated nuclear protein, YT521-B, and show that it interacts with the nuclear transcriptosomal component scaffold attachme...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.11.3909

    authors: Hartmann AM,Nayler O,Schwaiger FW,Obermeier A,Stamm S

    更新日期:1999-11-01 00:00:00

  • Saccharomyces cerevisiae PTS1 receptor Pex5p interacts with the SH3 domain of the peroxisomal membrane protein Pex13p in an unconventional, non-PXXP-related manner.

    abstract::A number of peroxisome-associated proteins have been described that are involved in the import of proteins into peroxisomes, among which is the receptor for peroxisomal targeting signal 1 (PTS1) proteins Pex5p, the integral membrane protein Pex13p, which contains an Src homology 3 (SH3) domain, and the peripheral memb...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.11.3963

    authors: Bottger G,Barnett P,Klein AT,Kragt A,Tabak HF,Distel B

    更新日期:2000-11-01 00:00:00

  • Rab GDI: a solubilizing and recycling factor for rab9 protein.

    abstract::Rab proteins are thought to function in the processes by which transport vesicles identify and/or fuse with their respective target membranes. The bulk of these proteins are membrane associated, but a measurable fraction can be found in the cytosol. The cytosolic forms of rab3A, rab11, and Sec4 occur as equimolar comp...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.4.4.425

    authors: Soldati T,Riederer MA,Pfeffer SR

    更新日期:1993-04-01 00:00:00

  • Cloning and functional characterization of mammalian homologues of the COPII component Sec23.

    abstract::We screened a human cDNA library with a probe derived from a partial SEC23 mouse homologue and isolated two different cDNA clones (hSec23A and hSec23B) encoding proteins of a predicted molecular mass of 85 kDa. hSec23Ap and hSec23Bp were 85% identical and shared 48% identity with the yeast Sec23p. Affinity-purified an...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.7.10.1535

    authors: Paccaud JP,Reith W,Carpentier JL,Ravazzola M,Amherdt M,Schekman R,Orci L

    更新日期:1996-10-01 00:00:00

  • Activity of a ubiquitin ligase adaptor is regulated by disordered insertions in its arrestin domain.

    abstract::The protein composition of the plasma membrane is rapidly remodeled in response to changes in nutrient availability or cellular stress. This occurs, in part, through the selective ubiquitylation and endocytosis of plasma membrane proteins, which in the yeast Saccharomyces cerevisiae is mediated by the HECT E3 ubiquiti...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E19-08-0451

    authors: Baile MG,Guiney EL,Sanford EJ,MacGurn JA,Smolka MB,Emr SD

    更新日期:2019-12-01 00:00:00

  • Agonist-induced PIP(2) hydrolysis inhibits cortical actin dynamics: regulation at a global but not at a micrometer scale.

    abstract::Phosphatidylinositol 4, 5-bisphosphate (PIP(2)) at the inner leaflet of the plasma membrane has been proposed to locally regulate the actin cytoskeleton. Indeed, recent studies that use GFP-tagged pleckstrin homology domains (GFP-PH) as fluorescent PIP(2) sensors suggest that this lipid is enriched in membrane microdo...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-04-0231

    authors: van Rheenen J,Jalink K

    更新日期:2002-09-01 00:00:00

  • Protein kinase Cdelta and calmodulin regulate epidermal growth factor receptor recycling from early endosomes through Arp2/3 complex and cortactin.

    abstract::The intracellular trafficking of the epidermal growth factor receptor (EGFR) is regulated by a cross-talk between calmodulin (CaM) and protein kinase Cdelta (PKCdelta). On inhibition of CaM, PKCdelta promotes the formation of enlarged early endosomes and blocks EGFR recycling and degradation. Here, we show that PKCdel...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-05-0411

    authors: Lladó A,Timpson P,Vilà de Muga S,Moretó J,Pol A,Grewal T,Daly RJ,Enrich C,Tebar F

    更新日期:2008-01-01 00:00:00

  • Glycolysis-dependent histone deacetylase 4 degradation regulates inflammatory cytokine production.

    abstract::Activation of the inflammatory response is accompanied by a metabolic shift to aerobic glycolysis. Here we identify histone deacetylase 4 (HDAC4) as a new component of the immunometabolic program. We show that HDAC4 is required for efficient inflammatory cytokine production activated by lipopolysaccharide (LPS). Surpr...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E13-12-0757

    authors: Wang B,Liu TY,Lai CH,Rao YH,Choi MC,Chi JT,Dai JW,Rathmell JC,Yao TP

    更新日期:2014-11-01 00:00:00

  • Syntaxin 6 and CAL mediate the degradation of the cystic fibrosis transmembrane conductance regulator.

    abstract::The PDZ domain-containing protein CAL mediates lysosomal trafficking and degradation of CFTR. Here we demonstrate the involvement of a CAL-binding SNARE protein syntaxin 6 (STX6) in this process. Overexpression of STX6, which colocalizes and coimmunoprecipitates with CAL, dramatically reduces the steady-state level an...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-03-0229

    authors: Cheng J,Cebotaru V,Cebotaru L,Guggino WB

    更新日期:2010-04-01 00:00:00

  • Intrinsically active variants of Erk oncogenically transform cells and disclose unexpected autophosphorylation capability that is independent of TEY phosphorylation.

    abstract::The receptor-tyrosine kinase (RTK)/Ras/Raf pathway is an essential cascade for mediating growth factor signaling. It is abnormally overactive in almost all human cancers. The downstream targets of the pathway are members of the extracellular regulated kinases (Erk1/2) family, suggesting that this family is a mediator ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E15-07-0521

    authors: Smorodinsky-Atias K,Goshen-Lago T,Goldberg-Carp A,Melamed D,Shir A,Mooshayef N,Beenstock J,Karamansha Y,Darlyuk-Saadon I,Livnah O,Ahn NG,Admon A,Engelberg D

    更新日期:2016-03-15 00:00:00

  • What makes the cell cycle tick? a celebration of the awesome power of biochemistry and the frog egg.

    abstract::The cell cycle, a 19th century discovery of cytologists, only achieved a satisfactory biochemical explanation in the last 20 years of the 20th century. This personal retrospective focuses on how biochemical studies of the frog egg helped identify the cyclin-based mitotic oscillator and how this approach quickly merged...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E20-10-0626

    authors: Kirschner M

    更新日期:2020-12-15 00:00:00

  • Ligand-dependent and -independent integrin focal contact localization: the role of the alpha chain cytoplasmic domain.

    abstract::Many integrin receptors localize to focal contact sites upon binding their ligand. However, unoccupied integrin receptors do not localize to focal contact sites. Because the integrin beta 1 cytoplasmic domain appears to have a focal contact localization signal, there must be a mechanism by which this domain is kept in...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.4.6.593

    authors: Briesewitz R,Kern A,Marcantonio EE

    更新日期:1993-06-01 00:00:00

  • A novel selection regime for differentiation defects demonstrates an essential role for the stumpy form in the life cycle of the African trypanosome.

    abstract::A novel selection scheme has been developed to isolate bloodstream forms of Trypanosoma brucei, which are defective in their ability to differentiate to the procyclic stage. Detailed characterization of one selected cell line (defective in differentiation clone 1 [DiD-1]) has demonstrated that these cells are indistin...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.5.1905

    authors: Tasker M,Wilson J,Sarkar M,Hendriks E,Matthews K

    更新日期:2000-05-01 00:00:00

  • Anchoring of protein kinase A-regulatory subunit IIalpha to subapically positioned centrosomes mediates apical bile canalicular lumen development in response to oncostatin M but not cAMP.

    abstract::Oncostatin M and cAMP signaling stimulate apical surface-directed membrane trafficking and apical lumen development in hepatocytes, both in a protein kinase A (PKA)-dependent manner. Here, we show that oncostatin M, but not cAMP, promotes the A-kinase anchoring protein (AKAP)-dependent anchoring of the PKA regulatory ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-08-0732

    authors: Wojtal KA,Hoekstra D,van Ijzendoorn SC

    更新日期:2007-07-01 00:00:00

  • A role for sorting nexin 2 in epidermal growth factor receptor down-regulation: evidence for distinct functions of sorting nexin 1 and 2 in protein trafficking.

    abstract::Sorting nexin 1 (SNX1) and SNX2, homologues of the yeast vacuolar protein-sorting (Vps)5p, contain a phospholipid-binding motif termed the phox homology (PX) domain and a carboxyl terminal coiled-coil region. A role for SNX1 in trafficking of cell surface receptors from endosomes to lysosomes has been proposed; howeve...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e03-09-0711

    authors: Gullapalli A,Garrett TA,Paing MM,Griffin CT,Yang Y,Trejo J

    更新日期:2004-05-01 00:00:00

  • Essential role of the p110beta subunit of phosphoinositide 3-OH kinase in male fertility.

    abstract::Phosphoinositide 3-kinases (PI3K) are key molecular players in male fertility. However, the specific roles of different p110 PI3K catalytic subunits within the spermatogenic lineage have not been characterized so far. Herein, we report that male mice expressing a catalytically inactive p110beta develop testicular hypo...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-08-0744

    authors: Ciraolo E,Morello F,Hobbs RM,Wolf F,Marone R,Iezzi M,Lu X,Mengozzi G,Altruda F,Sorba G,Guan K,Pandolfi PP,Wymann MP,Hirsch E

    更新日期:2010-03-01 00:00:00