RhoA/ROCK I signalling downstream of the P2Y13 ADP-receptor controls HDL endocytosis in human hepatocytes.


:Cell surface receptors for high-density lipoprotein (HDL) on hepatocytes are major partners in the regulation of cholesterol homeostasis. We have previously demonstrated on human hepatocytes that apolipoprotein A-I binding to an ectopic F(1)-ATPase stimulates the production of extracellular ADP that activates a P2Y(13)-mediated high-density lipoprotein (HDL) endocytosis pathway. However, P2Y(13)-dependent signalling pathway has never been described yet. The current study demonstrates a major role of cytoskeleton reorganization in F(1)-ATPase/P2Y(13)-dependent HDL endocytosis under the control of the small GTPase RhoA and its effector ROCK I. Indeed human hepatocytes (HepG(2) cells) stimulated by ADP or AR-C69931MX (both P2Y(13) agonists) showed a high specific activation of RhoA; in addition, inhibition of Rho proteins by C3 exoenzyme impairs HDL endocytosis whereas a constitutively active form of RhoA stimulates HDL endocytosis at the same level as under F(1)-ATPase/P2Y(13) activation. Pharmacological inhibition of ROCK activity decreased HDL endocytosis following stimulation by apoA-I (F(1)-ATPase ligand), ADP or AR-C69931MX and specific siRNA ROCK I extinction prevented the stimulation of HDL endocytosis without effect of ROCK II extinction. The functional involvement of ROCK I downstream F(1)-ATPase/P2Y(13) was confirmed by the strong enrichment of the membrane fraction in ROCK I and by the requirement of actin polymerization in hepatocyte HDL endocytosis. These results allow the identification of the molecular events downstream P2Y(13) receptor activation for a better understanding of hepatocyte HDL endocytosis, the latest step in reverse cholesterol transport.


Cell Signal


Cellular signalling


Malaval C,Laffargue M,Barbaras R,Rolland C,Peres C,Champagne E,Perret B,Tercé F,Collet X,Martinez LO




Has Abstract


2009-01-01 00:00:00














  • Glycogen synthase kinase-3 regulates microglial migration, inflammation, and inflammation-induced neurotoxicity.

    abstract::Microglia play a prominent role in the brain's inflammatory response to injury or infection by migrating to affected locations, secreting inflammatory molecules, and phagocytosing damaged tissue. However, because severe or chronic neuroinflammation exacerbates many neurological conditions, controlling microglia action...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Yuskaitis CJ,Jope RS

    更新日期:2009-02-01 00:00:00

  • Regulation of cellular functions by the ERK5 signalling pathway.

    abstract::Extracellular-regulated protein kinase 5 (ERK5) is a mitogen-activated protein kinase (MAPK) regulated by a wide range of mitogens and cellular stresses. Since its cloning in 1995, the lack of biological tools, including antibodies and specific inhibitors, have made it one of the least studied MAPK subfamilies. The di...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Wang X,Tournier C

    更新日期:2006-06-01 00:00:00

  • Vav proteins, masters of the world of cytoskeleton organization.

    abstract::Vav proteins are evolutionarily conserved from nematodes to mammals and play a pivotal role in many aspects of cellular signaling, coupling cell surface receptors to various effectors functions. In mammals, there are three family members; Vav1 is specifically expressed in the hematopoietic system, whereas Vav2 and Vav...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Hornstein I,Alcover A,Katzav S

    更新日期:2004-01-01 00:00:00

  • The role of sphingosine-1-phosphate in smooth muscle contraction.

    abstract::Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite that is known to mediate diverse cellular responses including cell growth, survival, and migration. Most of these effects have been attributed to its binding to a specific subfamily of G protein-coupled receptors (GPCR), namely S1P(1-5). Recent studi...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Watterson KR,Ratz PH,Spiegel S

    更新日期:2005-03-01 00:00:00

  • Native and iron-saturated bovine lactoferrin differently hinder migration in a model of human glioblastoma by reverting epithelial-to-mesenchymal transition-like process and inhibiting interleukin-6/STAT3 axis.

    abstract::Glioblastoma, the most lethal form of brain cancer, is characterized by fast growth, migration and invasion of the surrounding parenchyma, with epithelial-to-mesenchymal transition (EMT)-like process being mostly responsible for tumour spreading and dissemination. A number of actors, including cadherins, vimentin, tra...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Cutone A,Colella B,Pagliaro A,Rosa L,Lepanto MS,Bonaccorsi di Patti MC,Valenti P,Di Bartolomeo S,Musci G

    更新日期:2020-01-01 00:00:00

  • The SH3 domain of the S. cerevisiae Cdc25p binds adenylyl cyclase and facilitates Ras regulation of cAMP signalling.

    abstract::Cdc25 and Ras are two proteins required for cAMP signalling in the budding yeast Saccharomyces cerevisiae. Cdc25 is the guanine nucleotide exchange protein that activates Ras. Ras, in turn, activates adenylyl cyclase. Cdc25 has a Src homology 3 (SH3) domain near the N-terminus and a catalytic domain in the C-terminal ...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Mintzer KA,Field J

    更新日期:1999-02-01 00:00:00

  • Both EGFR kinase and Src-related tyrosine kinases regulate human ether-à-go-go-related gene potassium channels.

    abstract::Human ether-à-go-go-related gene (hERG or Kv11.1) encodes the rapidly activated delayed rectifier K(+) current (I(Kr)) in the human heart. Potential regulation of hERG channel by protein tyrosine kinases (PTKs) is not understood. The present study was designed to investigate whether this channel is modulated by PTKs u...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Zhang DY,Wang Y,Lau CP,Tse HF,Li GR

    更新日期:2008-10-01 00:00:00

  • Lithium enhances CRTC oligomer formation and the interaction between the CREB coactivators CRTC and CBP--implications for CREB-dependent gene transcription.

    abstract::Lithium salts are important drugs to treat bipolar disorder. Previous work showed that lithium by enforcing the interaction between the transcription factor CREB and its coactivator CRTC1 enhanced cAMP-stimulated CREB-dependent gene transcription. Both CREB and CRTC have been implicated in neuronal adaptation, which m...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Heinrich A,von der Heyde AS,Böer U,Phu do T,Tzvetkov M,Oetjen E

    更新日期:2013-01-01 00:00:00

  • Different phosphorylated forms of inositolphosphate glycan could be involved in the transforming growth factor-beta 1 (TGF-beta 1) signalling pathway.

    abstract::Labelling with [3H]glucosamine was used to prepare a transforming growth factor-beta 1 (TGF-beta 1)-sensitive glycosylphosphatidylinositol (GPI) from monolayer cultures of rabbit articular chondrocytes (RAC), which may be involved in control of the cell cycle. The polar headgroup of this glycosylphosphatidylinositol w...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Vivien D,Bogdanowicz P,Boumediene K,Martiny L,Haye B,Pujol JP

    更新日期:1994-02-01 00:00:00

  • Dual effect of formycin A upon the hydrolysis of phosphoinositides in perifused pancreatic islets.

    abstract::Formycin A (1.0 mM) caused a rapid, sustained and rapidly reversible inhibition of effluent radioactivity in rat pancreatic islets prelabelled with myo-[2-3H]inositol and perifused in the presence of 8.3 mM D-glucose. This coincided with a progressive decrease in islet ATP content and transient inhibition of insulin r...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Ulusoy S,Sener A,Malaisse WJ

    更新日期:1995-11-01 00:00:00

  • Testosterone- and phorbol ester-stimulated proliferation in human cultured prostatic stromal cells.

    abstract::Prostatic stromal proliferation may be commonly associated with the development of benign prostatic hyperplasia. In this study, we investigate the role of testosterone and protein kinase C in stimulating cultured stromal cell proliferation. Testosterone increased the uptake of [(3)H]-thymidine into the human cultured ...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Haynes JM,Frydenberg M,Majewski H

    更新日期:2001-10-01 00:00:00

  • Bacillus spore germination: Knowns, unknowns and what we need to learn.

    abstract::How might a microbial cell that is entirely metabolically dormant - and which has the ability to remain so for extended periods of time - irreversibly commit itself to resuming vegetative growth within seconds of being exposed to certain amino acids or sugars? That this process takes place in the absence of any detect...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Christie G,Setlow P

    更新日期:2020-10-01 00:00:00

  • Overexpression of dJmj differentially affects intestinal stem cells and differentiated enterocytes.

    abstract::Jumonji (Jmj)/Jarid2 is a DNA-binding transcriptional repressor mediated via histone methylation. Nevertheless, the well-known function of Jmj is as a scaffold for the recruitment of various complexes including Polycomb repressive complex 2 (PRC2), and required for mouse embryonic stem cell development. However, PRC2 ...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Suong DNA,Shimaji K,Pyo JH,Park JS,Yoshida H,Yoo MA,Yamaguchi M

    更新日期:2018-01-01 00:00:00

  • Multifaceted transforming growth factor-beta (TGFβ) signalling in glioblastoma.

    abstract::Glioblastoma (GBM) is an aggressive and devastating primary brain cancer which responds very poorly to treatment. The average survival time of patients is only 14-15 months from diagnosis so there is a clear and unmet need for the development of novel targeted therapies to improve patient outcomes. The multifunctional...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Birch JL,Coull BJ,Spender LC,Watt C,Willison A,Syed N,Chalmers AJ,Hossain-Ibrahim MK,Inman GJ

    更新日期:2020-08-01 00:00:00

  • Erythropoietin receptor-mediated Egr-1 activation: structural requirements and functional implications.

    abstract::The transcription factor Egr-1 is encoded by an immediate early response gene and has been shown to be a key regulator in the induction of apoptosis, mitogenesis and differentiation. It is rapidly induced by different stimuli including the glycoprotein hormone erythropoietin. In this report, we analyse the role of dif...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Schulze C,Büchse T,Mikkat S,Bittorf T

    更新日期:2008-10-01 00:00:00

  • Arf GAPs: multifunctional proteins that regulate membrane traffic and actin remodelling.

    abstract::The ADP-ribosylation factor (Arf) Arf GTPase-activating proteins (GAPs) are a family of proteins that induce hydrolysis of GTP bound to Arf. A conserved domain containing a zinc finger motif mediates catalysis. The substrate, Arf.GTP, affects membrane trafficking and actin remodelling. Consistent with activity as an A...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Randazzo PA,Hirsch DS

    更新日期:2004-04-01 00:00:00

  • CB₁ cannabinoid receptors promote maximal FAK catalytic activity by stimulating cooperative signaling between receptor tyrosine kinases and integrins in neuronal cells.

    abstract::Tyrosine phosphorylation (Tyr-P) of focal adhesion kinase (FAK) regulates FAK activation. Phosphorylated FAK Tyr 397 binds Src family kinases (Src), which in turn directly phosphorylate FAK Tyr 576/577 to produce maximal FAK enzymatic activity. CB₁ cannabinoid receptors (CB₁) are abundantly expressed in the nervous sy...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Dalton GD,Peterson LJ,Howlett AC

    更新日期:2013-08-01 00:00:00

  • A shift in the IL-6/STAT3 signalling pathway imbalance towards the SHP2 pathway in severe asthma results in reduced proliferation process.

    abstract:BACKGROUND:Bronchial fibroblasts are the main structural cells responsible for extracellular matrix production and turnover in lung tissue. They play a key role in airway remodelling in asthma through different cytokines including interleukin (IL-6). OBJECTIVE:To decipher IL-6 signalling in bronchial fibroblasts obtai...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Salem IH,Plante S,Gounni AS,Rouabhia M,Chakir J

    更新日期:2018-03-01 00:00:00

  • CRH suppressed TGFβ1-induced Epithelial-Mesenchymal Transition via induction of E-cadherin in breast cancer cells.

    abstract::Since its discovery in biopsies from breast cancer patients, the effect of corticotropin-releasing hormone (CRH) on carcinoma progression is still unclear. Transforming growth factorβ1 (TGFβ1) promotes Epithelial-Mesenchymal Transition (EMT) and induces Snail1 and Twist1 expressions. Loss of epithelial cadherin (E-cad...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Jin L,Chen J,Li L,Li C,Chen C,Li S

    更新日期:2014-04-01 00:00:00

  • Insulin activates caspase-3 by a phosphatidylinositol 3'-kinase-dependent pathway.

    abstract::Activation of the caspase proteases by c-Jun N-terminal kinase 1 (JNK1) has been proposed as a mechanism of apoptotic cell death. Here we report that insulin activates caspase-3 by a pathway requiring phosphatidylinositol 3'-kinase (PI3-kinase). JNK1 assays demonstrated that insulin treatment of myeloma cells induced ...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Godbout JP,Cengel KA,Cheng SL,Minshall C,Kelley KW,Freund GG

    更新日期:1999-01-01 00:00:00

  • CaMKIIδ interacts directly with IKKβ and modulates NF-κB signalling in adult cardiac fibroblasts.

    abstract::Calcium/calmodulin dependent protein kinase IIδ (CaMKIIδ) acts as a molecular switch regulating cardiovascular Ca2+ handling and contractility in health and disease. Activation of CaMKIIδ is also known to regulate cardiovascular inflammation and is reported to be required for pro-inflammatory NF-κB signalling. In this...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Martin TP,McCluskey C,Cunningham MR,Beattie J,Paul A,Currie S

    更新日期:2018-11-01 00:00:00

  • Interaction of angio-associated migratory cell protein with the TPα and TPβ isoforms of the human thromboxane A₂ receptor.

    abstract::In humans, thromboxane (TX) A₂ signals through the TPα and TPβ isoforms of its G-protein coupled TXA₂ receptor (TP) to mediate a host of (patho)physiologic responses. Herein, angio-associated migratory cell protein (AAMP) was identified as a novel interacting partner of both TPα and TPβ through an interaction dependen...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Reid HM,Wikström K,Kavanagh DJ,Mulvaney EP,Kinsella BT

    更新日期:2011-04-01 00:00:00

  • G proteins are involved in the suppression of collagen alpha 1 (I) gene expression in cultured rat hepatic stellate cells.

    abstract::We analyse the role of the G proteins in regulating collagen gene expression by measuring collagen alpha 1(I) mRNA levels in cultured hepatic stellate cells in basal conditions and after stimulating or inhibiting the major intracellular signalling pathways. Stimulation of Gs protein and adenylyl cyclase or the additio...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Solís-Herruzo JA,Hernández I,De la Torre P,García I,Sánchez JA,Fernández I,Castellano G,Muñoz-Yagüe T

    更新日期:1998-03-01 00:00:00

  • Synergistic effect of endothelin-1 and cyclic AMP on glucose transport in 3T3-L1 adipocytes.

    abstract::We have demonstrated previously that chronic exposure to endothlin-1 enhances glucose transport in 3T3-L1 adipocytes via augmented GLUT1 mRNA and protein accumulation. In the present study, we further examined the combined effect of endothelin-1 (ET-1) and cAMP on glucose transport. In cells pretreated with ET-1 and 8...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Fong JC,Kao YS,Tsai HY,Chiou YY,Chiou GY

    更新日期:2004-07-01 00:00:00

  • DAPk1 inhibits NF-κB activation through TNF-α and INF-γ-induced apoptosis.

    abstract::Recent studies have shown DAPk as a molecular modulator induced by the second messenger, responsible for controlling cell destiny decisions, but the detailed mechanism mediating the role of DAPk1 during cell death is still not fully understood. In this present report, we attempted to characterize the effects of TNF-α ...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Yoo HJ,Byun HJ,Kim BR,Lee KH,Park SY,Rho SB

    更新日期:2012-07-01 00:00:00

  • p130Cas: a key signalling node in health and disease.

    abstract::p130Cas/breast cancer anti-oestrogen resistance 1 (BCAR1) is a member of the Cas (Crk-associated substrate) family of adaptor proteins, which have emerged as key signalling nodes capable of interactions with multiple proteins, with important regulatory roles in normal and pathological cell function. The Cas family of ...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Barrett A,Pellet-Many C,Zachary IC,Evans IM,Frankel P

    更新日期:2013-04-01 00:00:00

  • Altered Gs alpha N-terminus affects Gs activity and interaction with the G beta gamma subunit complex in cell membranes but not in solution.

    abstract::The stimulatory G protein (Gs) mediates activation of adenylylcyclase by a ligand-receptor complex. Gs is heterotrimeric (alpha beta gamma) and activation can be accomplished by dissociation of the alpha-subunit (Gs alpha) from the beta gamma-subunit complex (G beta gamma). Gs alpha is also a substrate for choleragen ...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Warner DR,Okuya S,Rebois RV

    更新日期:1996-01-01 00:00:00

  • The duration of ERK1/2 activity determines the activation of c-Fos and Fra-1 and the composition and quantitative transcriptional output of AP-1.

    abstract::The duration of ERK1/2 activation influences the nature of the biological response to agonist. Members of the AP-1 transcription factor family are well known targets of the ERK1/2 pathway and are expressed in a temporally coordinated fashion during cell cycle re-entry. In CCl39 fibroblasts, sustained ERK1/2 activation...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Chalmers CJ,Gilley R,March HN,Balmanno K,Cook SJ

    更新日期:2007-04-01 00:00:00

  • The PI3 kinase-Akt pathway mediates Wnt3a-induced proliferation.

    abstract::Wnt3a activates proliferation of fibroblasts cells via activation of both extracellular signal-regulated kinase (ERK) and Wnt/beta-catenin signaling pathways. In this study, we show that the phosphatidyl inositol 3 kinases (PI3K)-Akt pathway is also involved in the Wnt3a-induced proliferation. Akt was activated within...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Kim SE,Lee WJ,Choi KY

    更新日期:2007-03-01 00:00:00

  • The characterisation of LATS2 kinase regulation in Hippo-YAP signalling.

    abstract::By controlling the YAP1 proto-oncoprotein Hippo signalling plays important roles in cancer-associated processes. Current evidence suggests that the Hippo kinases MST1/2 together with the MOB1 scaffold protein promote the formation of active MOB1/LATS complexes which phosphorylate and thereby inhibit YAP1. However, the...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Hoa L,Kulaberoglu Y,Gundogdu R,Cook D,Mavis M,Gomez M,Gomez V,Hergovich A

    更新日期:2016-05-01 00:00:00