Abstract:
:Both canonical Wnt/beta-catenin and TGFbeta/Smad signaling pathways coordinately regulate pattern formation during embryogenesis as well as tumor progression. Evidence of cross-talk between these two pathways has been reported. Here we demonstrated that the Activin-like kinase 4 (Alk4)/Smad2 pathway facilitates the transcriptional activity of the oncogenic Wnt/beta-catenin/Tcf4 pathway through a novel Smad4-independent mechanism. Upon activation, Smad2 physically interacted with Tcf4, beta-catenin and the co-activator p300 to enhance transcriptional activity of beta-catenin/Tcf4 through the histone acetyltransferase activity of p300. Transactivation by Smad2 was independent of a Smad-binding element (SBE) and Smad4. Indeed, the enhancement of beta-catenin/Tcf4 transcriptional activity by activated Smad2 was negatively regulated by the presence of Smad4. Moreover, a tumor-derived missense mutant of Smad2, lacking the ability to bind to Smad4 was still able to enhance the Tcf4 transcriptional reporter in the presence of beta-catenin and Tcf4. Our findings suggest that Smad2 may function as an activator of canonical Wnt/beta-catenin/Tcf4 signaling through a SBE/Smad4-independent pathway.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Hirota M,Watanabe K,Hamada S,Sun Y,Strizzi L,Mancino M,Nagaoka T,Gonzales M,Seno M,Bianco C,Salomon DSdoi
10.1016/j.cellsig.2008.05.003subject
Has Abstractpub_date
2008-09-01 00:00:00pages
1632-41issue
9eissn
0898-6568issn
1873-3913pii
S0898-6568(08)00151-4journal_volume
20pub_type
杂志文章abstract:BACKGROUND:All identified mammalian TRPC channels show a C-terminal calmodulin (CaM)- and inositol 1,4,5-trisphosphate receptors (IP(3)Rs)-binding (CIRB) site involved in the regulation of TRPC channel function. OBJECTIVES:To assess the basis of CaM/IP(3)Rs binding to the CIRB site of TRPC6 and its role in platelet ph...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.06.022
更新日期:2011-11-01 00:00:00
abstract::Loss of p53's tumor-suppressive function, either via TP53 mutation or hyperactive p53 inhibitory proteins, is one of the most frequent events in the development of human cancer. Here, we describe a strategy of pharmacologically inhibiting iASPP, a negative regulator of p53, to restore wild-type p53's tumor-suppressive...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2019.109508
更新日期:2020-03-01 00:00:00
abstract::Understanding how cells integrate signals from a variety of chemically diverse information-containing molecules into complex, orchestrated responses such as cell proliferation, differentiation and apoptosis is an overarching goal of cell biology. The ligand molecules that act upon cell surface receptors include those ...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/s0898-6568(97)00194-0
更新日期:1998-09-01 00:00:00
abstract::Cellular hypoxia can lead to cell death or adaptation and has important effects on development, physiology, and pathology. Here, we investigated the role and regulation of ceramide in hypoxia-induced apoptosis of SH-SY5Y neuroblastoma cells. Hypoxia increased the ceramide concentration; subsequently, we observed bioch...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.11.015
更新日期:2010-04-01 00:00:00
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
doi:10.1016/j.cellsig.2015.05.005
更新日期:2015-09-01 00:00:00
abstract::Lysophosphatidic acid (LPA) and its ether analog alkyl-glycerophosphate (AGP) elicit arterial wall remodeling when applied intralumenally into the uninjured carotid artery. LPA is the ligand of eight GPCRs and the peroxisome proliferator-activated receptor gamma (PPARgamma). We pursued a gene knockout strategy to iden...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.08.003
更新日期:2009-12-01 00:00:00
abstract::Certain TRP cation channels confer the ability to sense environmental stimuli (heat, cold, pressure, osmolarity) across physiological and pathophysiological ranges. TRPA1 is a TRP-related channel that responds to cold temperatures, and pungent compounds that include the cold-mimetic icilin and cannabinoids. The initia...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2005.12.009
更新日期:2006-10-01 00:00:00
abstract::Our previous oligonucleotide array studies revealed that ALK-positive anaplastic large cell lymphoma (ALK(+)ALCL) express high levels of the disheveled proteins (Dvls), a family of proteins that is integral to the Wnt signaling pathways. In this study, we assessed whether the Dvls are important in the pathogenesis of ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2012.09.027
更新日期:2013-01-01 00:00:00
abstract::Reduced connexin43 (Cx43) expression is frequently detected in different types of human cancer. Cx43 has been shown to regulate cancer cell migration in a cell-type dependent manner. In both primary and recurrent human ovarian cancer, overexpression of TGF-β ligand and its receptors have been detected. TGF-β can regul...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2015.07.010
更新日期:2015-10-01 00:00:00
abstract::Caveolin-1 (Cav-1) is a major structural protein of caveolae and plays an important role as a negative regulator of various signaling pathways such as the transforming growth factor-beta (TGF-beta)/smad pathway. In this study, we investigated the role of cav-1 on basal and TGF-beta1-induced expression of type I procol...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.02.020
更新日期:2008-07-01 00:00:00
abstract::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 th...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.12.005
更新日期:2009-04-01 00:00:00
abstract::The β-catenin signaling axis is critical for normal embryonic development and tissue homeostasis in adults. We have previously shown that extracellular enzyme transglutaminase 2 (TG2) activates β-catenin signaling in vascular smooth muscle cells (VSMCs). In this study, we provide several lines of evidence that TG2 fun...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.08.016
更新日期:2013-12-01 00:00:00
abstract::The earliest substrates to the transmembrane insulin receptor tyrosine kinase, that would function in insulin signalling, are likely to be associated with the plasma membrane. Rat liver plasma membrane 180,000 M(r) protein (p180) is a substrate to the insulin receptor in vitro [Goren et al. (1990) Cellular Signalling ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(93)90016-f
更新日期:1993-05-01 00:00:00
abstract::The present study has examined the effects of adenosine A1 receptors on second messenger processes in GH3 cells. A1 receptors are present which are shown to inhibit adenylate cyclase in a GTP-requiring manner. Hormone (VIP) stimulation is also absolutely required for the observation of inhibition. Adenosine A1 recepto...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(89)90023-5
更新日期:1989-01-01 00:00:00
abstract::Mitogen-activated protein (MAP) kinase cascades are signal transduction pathways that play pivotal regulatory roles in the biosynthesis of pro-inflammatory cytokines. MAP kinase phosphatase (MKP)-1, an archetypal member of the MKP family, is essential for the dephosphorylation/deactivation of MAP kinases p38 and JNK. ...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2007.03.013
更新日期:2007-07-01 00:00:00
abstract::Nuclear factor of activated T cells (NFATs) are crucial transcription factors that tightly control proinflammatory cytokine expression for adaptive immunity in T and B lymphocytes. However, little is known about the role of NFATs for innate immunity in macrophages. In this study, we report that NFAT is required for To...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.06.013
更新日期:2011-11-01 00:00:00
abstract::We employ a novel, dominant negative approach to identify a key role for certain tethered cyclic AMP specific phosphodiesterase-4 (PDE4) isoforms in regulating cyclic AMP dependent protein kinase A (PKA) sub-populations in resting COS1 cells. A fraction of PKA is clearly active in resting COS1 cells and this activity ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2005.04.003
更新日期:2005-09-01 00:00:00
abstract::mTORC2, the mammalian target of rapamycin complex 2 is activated by upstream growth factors, and performs two major functions, phosphorylation of AKT at the serine of 473 and cell cycle-dependent organization of actin cytoskeleton. However, the mechanisms through which mTORC2 is triggered by these signals remain uncle...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.07.008
更新日期:2013-11-01 00:00:00
abstract::Mechanical stretch is an initial factor for cardiac hypertrophy in response to haemodynamic overload (high blood pressure). Stretch of cardiomyocytes activates second messengers such as phosphatidylinositol, protein kinase C, Raf-1 kinase and extracellular signal-regulated protein kinases (ERKs), which are involved in...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/s0898-6568(98)00036-9
更新日期:1998-11-01 00:00:00
abstract::Nephrin, an important structural and signal molecule of podocyte slit-diaphragm (SD), has been suggested to contribute to the angiotensin II (Ang II)-induced podocyte injury. Caveolin-1 has been demonstrated to play a crucial role in signaling transduction. In the present study, we evaluated the role of caveolin-1 in ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.09.022
更新日期:2012-02-01 00:00:00
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
doi:10.1016/j.cellsig.2006.09.001
更新日期:2007-04-01 00:00:00
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
doi:10.1016/j.cellsig.2013.01.027
更新日期:2013-05-01 00:00:00
abstract::SCF induces autophosphorylation of Kit and activates a variety of signaling components including Jnks, Erks, PI 3 Kinase, the JAK-Stat pathway and members of the Src family. Previously we showed that Lyn is activated at multiple points during SCF-induced cell cycle progression and contributes to SCF-mediated growth, c...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2004.06.004
更新日期:2005-01-01 00:00:00
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
doi:10.1016/j.cellsig.2005.05.015
更新日期:2006-04-01 00:00:00
abstract::Rho GTPases are molecular switches involved in the regulation of many cellular processes. This review summarizes work examining how stimulation of receptor tyrosine kinases (RTKs) leads to the activation of Rho guanine nucleotide exchange factors (GEFs) and their Rho GTPase substrates. The collective findings strongly...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2006.01.022
更新日期:2006-11-01 00:00:00
abstract::The strong inhibition of thrombin-induced platelet functions induced by okadaic acid is not correlated with the partial modification of pleckstrin phosphorylation, which remains still phosphorylated two min after stimulation, indicating that protein kinase C is not affected by okadaic acid. We then investigated the ef...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(96)00119-2
更新日期:1997-01-01 00:00:00
abstract::Receptor for Activated C-Kinase 1 (RACK1) belongs to the WD40 family of proteins, known to act as scaffolding proteins in interaction networks. Accordingly, RACK1 is found to have numerous interacting partners ranging from kinases and signaling proteins to membrane bound receptors and ion channels. Interestingly, RACK...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2017.01.026
更新日期:2017-07-01 00:00:00
abstract::Akt (also known as protein kinase B or PKB) comprises three closely related isoforms Akt1, Akt2 and Akt3 (or PKBα/β/γ respectively). We have a very good understanding of the mechanisms by which Akt isoforms are activated by growth factors and other extracellular stimuli as well as by oncogenic mutations in key upstrea...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2011.05.004
更新日期:2011-10-01 00:00:00
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
doi:10.1016/j.cellsig.2016.02.011
更新日期:2016-05-01 00:00:00
abstract::Signal transducer and activator of transcription 3 (Stat3) is a transcription factor that is involved in cell survival and proliferation and has been found to be persistently activated in most human cancers mainly through its phosphorylation at Tyr-705. However, the role and regulation of Stat3 Ser-727 phosphorylation...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.04.003
更新日期:2014-08-01 00:00:00