Lysophosphatidic acid induces Ca2+ mobilization and c-Myc expression in mouse embryonic stem cells via the phospholipase C pathway.


:Embryonic stem cells (ESC) are pluripotent and could be maintained in vitro in a self-renewing state indefinitely, at the same time preserving their potential to differentiate towards more specific lineages. Despite the progress in the field, the complex network of signalling cascades involved in the maintenance of the self-renewing and pluripotent state remains not fully understood. In the present study, we have investigated the role of lysophosphatidic acid (LPA), a potent mitogen present in serum, in Ca(2+) signalling and early gene activation in mouse ESC (mESC). In these cells, we detected the expression of the G-protein coupled LPA receptor subtypes LPA(1), LPA(2) and LPA(3). Using fluorescence Ca(2+) imaging techniques, we showed that LPA induced an increase in intracellular Ca(2+) concentration. This increase was also observed in the absence of extracellular Ca(2+), suggesting the involvement of internal stores. Pre-treatment with BAPTA-AM, thapsigargin or U-73122 efficiently blocked this Ca(2+) release, indicating that LPA was evoking Ca(2+) mobilization from the endoplasmic reticulum via the phospholipase C (PLC) pathway. Interestingly, this signalling cascade initiated by LPA was involved in inducing the expression of the Ca(2+)-dependent early response gene c-myc, a key gene implicated in ESC self-renewal and pluripotency. Additionally, LPA increased the proliferation rate of mESC. Our findings therefore outline the physiological role of LPA in mESC.


Cell Signal


Cellular signalling


Todorova MG,Fuentes E,Soria B,Nadal A,Quesada I




Has Abstract


2009-04-01 00:00:00














  • Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity.

    abstract::Apremilast, an oral small molecule inhibitor of phosphodiesterase 4 (PDE4), is in development for chronic inflammatory disorders, and has shown efficacy in psoriasis, psoriatic arthropathies, and Behçet's syndrome. In March 2014, the US Food and Drug Administration approved apremilast for the treatment of adult patien...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Schafer PH,Parton A,Capone L,Cedzik D,Brady H,Evans JF,Man HW,Muller GW,Stirling DI,Chopra R

    更新日期:2014-09-01 00:00:00

  • Review: ER stress-induced cell death in osteoarthritic cartilage.

    abstract::In cartilage, chondrocytes are responsible for the biogenesis and maintenance of the extracellular matrix (ECM) composed of proteins, glycoproteins and proteoglycans. Various cellular stresses, such as hypoxia, nutrient deprivation, oxidative stress or the accumulation of advanced glycation end products (AGEs) during ...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Rellmann Y,Eidhof E,Dreier R

    更新日期:2021-02-01 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

  • 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

  • KLF4 overcomes tamoxifen resistance by suppressing MAPK signaling pathway and predicts good prognosis in breast cancer.

    abstract::Tamoxifen resistance represents a daunting challenge to the successful treatment for breast cancer. Krüppel-like factor 4 has critical roles in the development and progression of breast cancer, but its expression, function and regulation in the efficacy of TAM therapy in breast cancer have yet to be investigated. Here...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Jia Y,Zhou J,Luo X,Chen M,Chen Y,Wang J,Xiong H,Ying X,Hu W,Zhao W,Deng W,Wang L

    更新日期:2018-01-01 00:00:00

  • Steering signal transduction pathway towards cardiac lineage from human pluripotent stem cells: a review.

    abstract::In humans injured myocardium cannot avert the onset and progression of ventricular dysfunction because of limited regenerative ability of myocytes. Although limited renaissance of cardiomyocytes has been reported in human infarcted hearts, it is generally accredited that non-functional fibrous tissue replaces the dead...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Verma V,Purnamawati K,Manasi,Shim W

    更新日期:2013-05-01 00:00:00

  • Mechanism of phospholipase D activation induced by prostaglandin D2 in osteoblast-like cells: function of Ca2+/calmodulin.

    abstract::Prostaglandin D2 (PGD2) stimulated the formation of choline in a dose-dependent manner in the range between 10 nM and 10 microM. The effect of PGD2 on the formation of inositol phosphates (EC50 was 20 nM) was more potent than that on the formation of choline (EC50 was 0.5 microM). The formation of choline stimulated b...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Imamura Y,Kozawa O,Suzuki A,Watanabe Y,Saito H,Oiso Y

    更新日期:1995-01-01 00:00:00

  • A crosstalk between TGF-β/Smad3 and Wnt/β-catenin pathways promotes vascular smooth muscle cell proliferation.

    abstract:RATIONALE:Endovascular interventions performed for atherosclerotic lesions trigger excessive vascular smooth muscle cell (SMC) proliferation leading to intimal hyperplasia. Our previous studies show that following endovascular injury, elevated TGF-β/Smad3 promotes SMC proliferation and intimal hyperplasia. Furthermore ...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: DiRenzo DM,Chaudhary MA,Shi X,Franco SR,Zent J,Wang K,Guo LW,Kent KC

    更新日期:2016-05-01 00:00:00

  • Characteristics of circular RNAs generated by human Survival Motor Neuron genes.

    abstract::Circular RNAs (circRNAs) belong to a diverse class of stable RNAs expressed in all cell types. Their proposed functions include sponging of microRNAs (miRNAs), sequestration and trafficking of proteins, assembly of multimeric complexes, production of peptides, and regulation of transcription. Backsplicing due to RNA s...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Ottesen EW,Singh RN

    更新日期:2020-09-01 00:00:00

  • Negative regulation of Jak2 by its auto-phosphorylation at tyrosine 913 via the Epo signaling pathway.

    abstract::Janus kinase 2 (Jak2) has a pivotal role in erythropoietin (Epo) signaling pathway, including erythrocyte differentiation and Stat5 activation. In the course of screening for critical phosphorylation of tyrosine residues in Jak2, we identified tyrosine 913 (Y(913)) as a novel and functional phosphorylation site, which...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Funakoshi-Tago M,Tago K,Kasahara T,Parganas E,Ihle JN

    更新日期:2008-11-01 00:00:00

  • Differential regulation and role of interleukin-1 receptor associated kinase-M in innate immunity signaling.

    abstract::Toll-like-receptor mediated signaling is finely regulated by a complex intracellular protein network including the interleukin-1 receptor associate kinases (IRAKs). IRAK-4, 1, and 2 may positively regulate innate immunity signaling through the activation of various downstream kinases such as MAPKs. In contrast, IRAK-M...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Su J,Xie Q,Wilson I,Li L

    更新日期:2007-07-01 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

  • Insight into the therapeutic aspects of 'Zeta-Chain Associated Protein Kinase 70 kDa' inhibitors: a review.

    abstract::Zeta-Chain Associated Protein Kinase 70 kDa (ZAP-70), a member of Syk family (non-receptor protein tyrosine kinase family), has an imperative function in the immune cell signaling in T cells. Its role in T-cell development has been established by the severe combined immune deficiency syndrome in ZAP-70 deficient human...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Kaur M,Singh M,Silakari O

    更新日期:2014-11-01 00:00:00

  • Function of phosducin-like proteins in G protein signaling and chaperone-assisted protein folding.

    abstract::Members of the phosducin gene family were initially proposed to act as down-regulators of G protein signaling by binding G protein betagamma dimers (Gbetagamma) and inhibiting their ability to interact with G protein alpha subunits (Galpha) and effectors. However, recent findings have over-turned this hypothesis by sh...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Willardson BM,Howlett AC

    更新日期:2007-12-01 00:00:00

  • CD40 mediated human cholangiocyte apoptosis requires JAK2 dependent activation of STAT3 in addition to activation of JNK1/2 and ERK1/2.

    abstract::CD40 is critically involved in Fas-mediated cholangiocyte apoptosis during liver inflammation, but the underlying signalling events are poorly understood. Our recent work implicated AP-1 in CD40-induced cholangiocyte apoptosis, but suggested involvement of other signalling pathways. Because STAT3 has been implicated i...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Ahmed-Choudhury J,Williams KT,Young LS,Adams DH,Afford SC

    更新日期:2006-04-01 00:00:00

  • Calcineurin activates NF-kappaB in skeletal muscle C2C12 cells.

    abstract::Calcineurin (CnA) is an important signalling molecule in skeletal muscle, in the promotion of differentiation, slow-fibre phenotype and possibly fibre hypertrophy. We found that stable expression of constitutively active CnA in muscle C2C12 cells strongly activated NF-kappaB, a key mediator of muscle wasting. NF-kappa...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Alzuherri H,Chang KC

    更新日期:2003-05-01 00:00:00

  • Actinomycin D and nutlin-3a synergistically promote phosphorylation of p53 on serine 46 in cancer cell lines of different origin.

    abstract::The p53 tumor suppressor protein is a transcription factor activated by phosphorylation of its N-terminus. MDM2, encoded by a p53-activated gene, acts as a negative-feedback regulator of p53 by promoting p53 degradation. Moreover, MDM2 inhibits p53 by binding to and concealing its N-terminal transcription-activating d...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Zajkowicz A,Gdowicz-Kłosok A,Krześniak M,Ścieglińska D,Rusin M

    更新日期:2015-09-01 00:00:00

  • Cellular processes involved in human epidermal cells exposed to extremely low frequency electric fields.

    abstract::We observed on different tissues and organisms a biological response after exposure to pulsed low frequency and low amplitude electric or electromagnetic fields but the precise mechanism of cell response remains unknown. The aim of this publication is to understand, using bioinformatics, the biological relevance of pr...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Collard JF,Hinsenkamp M

    更新日期:2015-05-01 00:00:00

  • Studies on the effect of diadenlyated nucleotides on calcium mobilization and prostacyclin synthesis in bovine aortic endothelial cells.

    abstract::Extracellular adenine dinucleotides are modulators of blood vessel tone. We have previously demonstrated that Ap(2)A and Ap(4)A induce the synthesis of nitric oxide (NO) from bovine aortic endothelial cells (BAEC) while Ap(3)A and Ap(5)A do not [FEBS Lett. 427 (1998) 320; Arch. Biochem. Biophys. 364 (1999) 280.]. In t...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Haghiac M,Pojoga LH,Hilderman RH

    更新日期:2001-02-01 00:00:00

  • MyD88, IRAK1 and TRAF6 knockdown in human chondrocytes inhibits interleukin-1-induced matrix metalloproteinase-13 gene expression and promoter activity by impairing MAP kinase activation.

    abstract::Interleukin-1 (IL-1) is the major prototypic proinflammatory cytokine that stimulates degradation of cartilage in arthritis by inducing prominent collagen II-degrading matrix metalloproteinase-13 (MMP-13). Nothing is known about the involvement of adaptor proteins, MyD88, IRAK1 and TRAF6 in MMP-13 regulation. Here we ...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Ahmad R,Sylvester J,Zafarullah M

    更新日期:2007-12-01 00:00:00

  • GADS is required for TCR-mediated calcium influx and cytokine release, but not cellular adhesion, in human T cells.

    abstract::GRB2 related adaptor protein downstream of Shc (GADS) is a member of the GRB2 family of adaptors and is critical for TCR-induced signaling. The current model is that GADS recruits SLP-76 to the LAT complex, which facilitates the phosphorylation of SLP-76, the activation of PLC-γ1, T cell adhesion and cytokine producti...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Bilal MY,Zhang EY,Dinkel B,Hardy D,Yankee TM,Houtman JC

    更新日期:2015-04-01 00:00:00

  • TMC8 (EVER2) attenuates intracellular signaling by Zn2+ and Ca2+ and suppresses activation of Cl- currents.

    abstract::Eight paralogue members form the family of transmembrane channel-like (TMC) proteins that share considerable sequence homology to anoctamin 1 (Ano1, TMEM16A). Ano1 is a Ca(2+) activated Cl(-) channel that is related to head and neck cancer, often caused by human papilloma virus (HPV) infection. Mutations in TMC 6 and ...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Sirianant L,Ousingsawat J,Tian Y,Schreiber R,Kunzelmann K

    更新日期:2014-12-01 00:00:00

  • Phosphorylation on the Ser 824 residue of TRPV4 prefers to bind with F-actin than with microtubules to expand the cell surface area.

    abstract::Previously, we demonstrated that the transient receptor potential vanilloid 4 (TRPV4) cation channel, a member of the TRP vanilloid subfamily, is one of the serum glucocorticoid-induced protein kinase1 (SGK1) authentic substrate proteins, and that the Ser 824 residue of TRPV4 is phosphorylated by SGK1. In this study, ...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Shin SH,Lee EJ,Hyun S,Chun J,Kim Y,Kang SS

    更新日期:2012-03-01 00:00:00

  • Suppression of adenylyl cyclase-mediated cAMP production by plasma membrane associated cytoskeletal protein 4.1G.

    abstract::It has been shown lately that activity of G protein-coupled receptors (GPCRs) is regulated by an array of proteins binding to carboxy (C)-terminus of GPCRs. Proteins of 4.1 family are subsets of subcortical cytoskeletal proteins and are known to stabilize cellular structures and proteins at the plasma membrane. One of...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Goto T,Chiba A,Sukegawa J,Yanagisawa T,Saito M,Nakahata N

    更新日期:2013-03-01 00:00:00

  • Downregulation of stathmin expression is mediated directly by Egr1 and associated with p53 activity in lung cancer cell line A549.

    abstract::Stathmin is overexpressed in a variety of assessed human malignancies and is correlated with tumor progression and poor prognosis. Downregulation of its expression will contribute to optimize therapeutic outcomes in the treatment of various malignancies. However, the mechanisms of stathmin gene overexpression are not ...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Fang L,Min L,Lin Y,Ping G,Rui W,Ying Z,Xi W,Ting H,Li L,Ke D,Jihong R,Huizhong Z

    更新日期:2010-01-01 00:00:00

  • Concurrent activation of β2-adrenergic receptor and blockage of GPR55 disrupts pro-oncogenic signaling in glioma cells.

    abstract::Activation of β2-adrenergic receptor (β2AR) and deorphanized GPR55 has been shown to modulate cancer growth in diverse tumor types in vitro and in xenograft models in vivo. (R,R')-4'-methoxy-1-naphthylfenoterol [(R,R')-MNF] is a bivalent compound that agonizes β2AR but inhibits GPR55-mediated pro-oncogenic responses. ...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Wnorowski A,Such J,Paul RK,Wersto RP,Indig FE,Jozwiak K,Bernier M,Wainer IW

    更新日期:2017-08-01 00:00:00

  • NOK associates with c-Src and promotes c-Src-induced STAT3 activation and cell proliferation.

    abstract::Signal transducers and activators of transcription 3 (STAT3) is reported to regulate cell proliferation, survival, and differentiation, and thus plays a central role in development and carcinogenesis. Accumulating evidence demonstrated the involvement of cellular Src (c-Src) tyrosine kinase in the activation of STAT3....

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Wang Y,Liu S,Jiang G,Zhai W,Yang L,Li M,Chang Z,Zhu B

    更新日期:2020-11-01 00:00:00

  • Recent progress toward understanding the molecular mechanisms that regulate skeletal muscle mass.

    abstract::The maintenance of muscle mass is critical for health and issues associated with the quality of life. Over the last decade, extensive progress has been made with regard to our understanding of the molecules that regulate skeletal muscle mass. Not surprisingly, many of these molecules are intimately involved in the reg...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Goodman CA,Mayhew DL,Hornberger TA

    更新日期:2011-12-01 00:00:00

  • The role of the PH domain and SH3 binding domains in dynamin function.

    abstract::Dynamin, a 100 kD GTPase, is necessary for the normal development and function of mammalian neural tissue. In neurons, it is necessary for the biogenesis of synaptic vesicles, and in other cell types dynamin has a general and important role in clathrin mediated receptor endocytosis. Different isoforms function as mole...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Scaife RM,Margolis RL

    更新日期:1997-09-01 00:00:00

  • Early growth response gene 1, a TRBP binding protein, is involved in miRNA activity of miR-125a-3p in human cells.

    abstract:BACKGROUND:MicroRNAs (miRNAs) are key regulators of many cellular pathways. However, the picture for components or regulators involved in the process of miRNA biogenesis and function remains to be further elucidated. Early growth response gene 1 (Egr1) has long been considered as tumor suppressor and transcriptional fa...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Wei J,Ouyang Y,Li X,Zhu B,Yang J,Cui Y,Chen X,Lin F,Long M,Yang A,Dong K,Zhang H

    更新日期:2015-06-01 00:00:00