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    4604 results match your criteria Cellular Signalling [Journal]

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    The IL-6/STAT3 pathway regulates adhesion molecules and cytoskeleton of endothelial cells in thromboangiitis obliterans.
    Cell Signal 2018 Jan 12. Epub 2018 Jan 12.
    Key Laboratory of Hepatosplenic Surgery, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Electronic address:
    Thromboangiitis obliterans (TAO) (also known as Buerger's disease) is an inflammatory vascular disease that predominantly affects small- and medium-sized blood vessels of extremities. Endothelial cells play critical roles in the initiation and progression of this disease, but the underlying mechanisms remain unclear. In the present study, we demonstrate that patients with TAO had significantly higher levels of interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in their plasmas, and the involved arterial tissues expressed higher levels of phosphorylated signal transducer and activator of transcription 3 (p-STAT3), ICAM-1 and VCAM-1. Read More

    Wnt5a mediates chronic post-thoracotomy pain by regulating non-canonical pathways, nerve regeneration, and inflammation in rats.
    Cell Signal 2018 Jan 12. Epub 2018 Jan 12.
    Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address:
    As well-characterized ligands involved in neurogenesis, Wnts are emerging as promising targets in pain pathogenesis. Our previous pilot study showed that intrathecal inhibition of Wnt5a, but not Wnts, relieves chronic post-thoracotomy pain (CPTP) in rats. In the present study, we aimed to further explore the regulatory mechanism of Wnt5a in CPTP development. Read More

    miR-613 inhibits cell migration and invasion by downregulating Daam1 in triple-negative breast cancer.
    Cell Signal 2018 Jan 12;44:33-42. Epub 2018 Jan 12.
    Department of Physiology, Nanjing Medical University, Nanjing 211166, Jiangsu, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, Jiangsu, China. Electronic address:
    Dishevelled-associated activator of morphogenesis 1 (Daam1) is a formin protein and participates in regulating cell migration of triple-negative breast cancer (TNBC) cells. The specific miRNA targeting Daam1 and mediating cell migration and invasion remains obscure. This experiment investigated the suppressive role of miR-613 in TNBC cells. Read More

    miRNA15a regulates insulin signal transduction in the retinal vasculature.
    Cell Signal 2018 Jan 12. Epub 2018 Jan 12.
    Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI, United States; Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI, United States. Electronic address:
    We previously reported that tumor necrosis factor alpha (TNFα) could inhibit insulin signal transduction in retinal cells. We recently found that miR15a/16 also reduced TNFα in retinal endothelial cells (REC) and in vascular specific miR15a/16 knockout mice. Since in silico programs suggested that miR15a could directly bind the insulin receptor, we wanted to determine whether miR15a altered insulin signal transduction. Read More

    Lysophosphatidic acid regulates the motility of MCF10CA1a breast cancer cell sheets via two opposing signaling pathways.
    Cell Signal 2018 Jan 11. Epub 2018 Jan 11.
    Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States. Electronic address:
    Aberrant cell migration leads to the dispersal of malignant cells. The ubiquitous lipid mediator lysophosphatidic acid (LPA) modulates cell migration and is implicated in tumor progression. Yet, the signaling cascades that regulate LPA's effect on cell motility remain unclear. Read More

    Membrane-permeable Rab27A is a regulator of the acrosome reaction: Role of geranylgeranylation and guanine nucleotides.
    Cell Signal 2018 Jan 11. Epub 2018 Jan 11.
    Instituto de Histologia y Embriologia de Mendoza (IHEM) Dr. Mario H. Burgos-CONICET, Universidad Nacional de Cuyo, casilla de correo 56, 5500 Mendoza, Argentina. Electronic address:
    The acrosome reaction is the regulated exocytosis of mammalian sperm's single secretory granule, essential for fertilization. It relies on small GTPases, the cAMP binding protein Epac, and the SNARE complex, among other components. Here, we describe a novel tool to investigate Rab27-related signaling pathways: a hybrid recombinant protein consisting of human Rab27A fused to TAT, a cell penetrating peptide. Read More

    Cathepsin L promotes ionizing radiation-induced U251 glioma cell migration and invasion through regulating the GSK-3β/CUX1 pathway.
    Cell Signal 2018 Jan 10. Epub 2018 Jan 10.
    Department of pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, China. Electronic address:
    Cathepsin L (CTSL) is a lysosomal cysteine protease overexpressed and secreted by tumor cells. Our previous study found that CTSL was involved in ionizing radiation (IR)-induced epithelial-mesenchymal transition (EMT) and the increase of glioma invasion and migration. However, the mechanisms by which CTSL promoted this IR-induced glioma migration and invasion remained unclear. Read More

    Protein neddylation and its alterations in human cancers for targeted therapy.
    Cell Signal 2018 Jan 10. Epub 2018 Jan 10.
    Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address:
    Neddylation, a post-translational modification that conjugates an ubiquitin-like protein NEDD8 to substrate proteins, is an important biochemical process that regulates protein function. The best-characterized substrates of neddylation are the cullin subunits of Cullin-RING ligases (CRLs), which, as the largest family of E3 ubiquitin ligases, control many important biological processes, including tumorigenesis, through promoting ubiquitylation and subsequent degradation of a variety of key regulatory proteins. Recently, increasing pieces of experimental evidence strongly indicate that the process of protein neddylation modification is elevated in multiple human cancers, providing sound rationale for its targeting as an attractive anticancer therapeutic strategy. Read More

    Importins α and β signaling mediates endothelial cell inflammation and barrier disruption.
    Cell Signal 2018 Jan 10. Epub 2018 Jan 10.
    Department of Pediatrics (Neonatology), Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, United States. Electronic address:
    Nucleocytoplasmic shuttling via importins is central to the function of eukaryotic cells and an integral part of the processes that lead to many human diseases. In this study, we addressed the role of α and β importins in the mechanism of endothelial cell (EC) inflammation and permeability, important pathogenic features of many inflammatory diseases such as acute lung injury and atherosclerosis. RNAi-mediated knockdown of importin α4 or α3 each inhibited NF-κB activation, proinflammatory gene (ICAM-1, VCAM-1, and IL-6) expression, and thereby endothelial adhesivity towards HL-60 cells, upon thrombin challenge. Read More

    Inositol polyphosphates contribute to cellular circadian rhythms: Implications for understanding lithium's molecular mechanism.
    Cell Signal 2018 Jan 10. Epub 2018 Jan 10.
    Research and Psychiatry Service, Veterans Affairs San Diego Healthcare System, 3350 La Jolla Village Dr, San Diego, CA 92161, United States; Department of Psychiatry and Center for Circadian Biology, University of California San Diego, 9500 Gilman Dr La Jolla, CA 92093, United States. Electronic address:
    Most living organisms maintain cell autonomous circadian clocks that synchronize critical biological functions with daily environmental cycles. In mammals, the circadian clock is regulated by inputs from signaling pathways including glycogen synthase kinase 3 (GSK3). The drug lithium has actions on GSK3, and also on inositol metabolism. Read More

    Compartmentalized crosstalk of CFTR and TMEM16A (ANO1) through EPAC1 and ADCY1.
    Cell Signal 2018 Jan 10;44:10-19. Epub 2018 Jan 10.
    Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany. Electronic address:
    Airway epithelial cells express both Ca2+ activated TMEM16A/ANO1 and cAMP activated CFTR anion channels. Previous work suggested a significant crosstalk of intracellular Ca2+ and cAMP signaling pathways, leading to activation of both chloride channels. We demonstrate that in airway epithelial cells, stimulation of purinergic or muscarinic G-protein coupled receptors (GPCRs) activates TMEM16A and CFTR. Read More

    LPA-induced migration of ovarian cancer cells requires activation of ERM proteins via LPA1 and LPA2.
    Cell Signal 2018 Jan 9. Epub 2018 Jan 9.
    Department of Brain-Cognitive Sciences, Daegu-Gyeongbuk Institute of Science and Technology (DGIST), Hyeonpung-myeon, Dalseong-gun, Daegu, Republic of Korea. Electronic address:
    Lysophosphatidic acid (LPA) has been implicated in the pathology of human ovarian cancer. This phospholipid elicits a wide range of cancer cell responses, such as proliferation, trans-differentiation, migration, and invasion, via various G-protein-coupled LPA receptors (LPARs). Here, we explored the cellular signaling pathway via which LPA induces migration of ovarian cancer cells. Read More

    Dopamine transporter trafficking is regulated by neutral sphingomyelinase 2/ceramide kinase.
    Cell Signal 2018 Jan 9. Epub 2018 Jan 9.
    Department of Environmental & Health Chemistry, College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-Ku, Seoul 06974, South Korea. Electronic address:
    Dopamine (DA) reuptake is the primary mechanism to terminate dopaminergic transmission in the synaptic cleft. The dopamine transporter (DAT) has an important role in the regulation of DA reuptake. This study provides anatomical and physiological evidence that DAT recycling is regulated by ceramide kinase via the sphingomyelin pathway. Read More

    Oncogenic RAC1 and NRAS drive resistance to endoplasmic reticulum stress through MEK/ERK signalling.
    Cell Signal 2018 Jan 9. Epub 2018 Jan 9.
    The Institute of Cancer Research, 15 Cotswold Road, Sutton SM2 5NG, UK.
    Cancer cells are able to survive under conditions that cause endoplasmic reticulum stress (ER-stress), and can adapt to this stress by upregulating cell-survival signalling pathways and down-regulating apoptotic pathways. The cellular response to ER-stress is controlled by the unfolded protein response (UPR). Small Rho family GTPases are linked to many cell responses including cell growth and apoptosis. Read More

    Receptor- and cellular compartment-specific activation of the cAMP/PKA pathway by α1-adrenergic and ETA endothelin receptors.
    Cell Signal 2018 Jan 9. Epub 2018 Jan 9.
    Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada. Electronic address:
    The signaling functions of many G protein-coupled receptors (GPCRs) expressed in the myocardium are incompletely understood. Among these are the endothelin receptor (ETR) family and α1-adrenergic receptor (α1-AR), which are thought to couple to the G protein Gαq. In this study, we used transcriptome analysis to compare the signaling networks downstream of these receptors in primary neonatal rat cardiomyocytes. Read More

    Nogo-A interacts with TrkA to alter nerve growth factor signaling in Nogo-A-overexpressing PC12 cells.
    Cell Signal 2018 Jan 8;44:20-27. Epub 2018 Jan 8.
    Research Service, Edward Hines Jr. Veterans Administration Hospital, Hines, IL 60141, USA; Department of Molecular Pharmacology and Therapeutics, Loyola University Medical Center, Maywood, IL, USA. Electronic address:
    The Nogo-A protein, originally discovered as a potent myelin-associated inhibitor of neurite outgrowth, is also expressed by certain neurons, especially during development and after injury, but its role in neuronal function is not completely known. In this report, we overexpressed Nogo-A in PC12 cells to use as a model to identify potential neuronal signaling pathways affected by endogenously expressed Nogo-A. Unexpectedly, our results show that viability of Nogo-A-overexpressing cells was reduced progressively due to apoptotic cell death following NGF treatment, but only after 24 h. Read More

    HBP induces the expression of monocyte chemoattractant protein-1 via the FAK/PI3K/AKT and p38 MAPK/NF-κB pathways in vascular endothelial cells.
    Cell Signal 2018 Mar 27;43:85-94. Epub 2017 Dec 27.
    Department of Burn and Plastic Surgery, Shanghai Jiao Tong University, School of Medicine, Rui Jin Hospital, Shanghai, China. Electronic address:
    Inflammation is characterized by early influx of polymorphonuclear neutrophils (PMNs), followed by a second wave of monocyte recruitment. PMNs mediate monocyte recruitment via their release of heparin binding protein (HBP), which activates CCR2 (CC-chemokine receptor 2) on monocytes. However, the pathways for such signal transmission remain unknown. Read More

    Coordinated d-cyclin/Foxd1 activation drives mitogenic activity of the Sonic Hedgehog signaling pathway.
    Cell Signal 2017 Dec 26;44:1-9. Epub 2017 Dec 26.
    Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, United States; Molecular and Environmental Toxicology Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States. Electronic address:
    Sonic Hedgehog (Shh) signaling plays key regulatory roles in embryonic development and postnatal homeostasis and repair. Modulation of the Shh pathway is known to cause malformations and malignancies associated with dysregulated tissue growth. However, our understanding of the molecular mechanisms by which Shh regulates cellular proliferation is incomplete. Read More

    Biased G protein-coupled receptor agonism mediates Neu1 sialidase and matrix metalloproteinase-9 crosstalk to induce transactivation of insulin receptor signaling.
    Cell Signal 2018 Mar 24;43:71-84. Epub 2017 Dec 24.
    Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario K7L3N6, Canada. Electronic address:
    G protein-coupled receptors (GPCR) can participate in a number of signaling pathways, and this property led to the concept of biased GPCR agonism. Agonists, antagonists and allosteric modulators can bind to GPCRs in different ways, creating unique conformations that differentially modulate signaling through one or more G proteins. A unique neuromedin B (NMBR) GPCR-signaling platform controlling mammalian neuraminidase-1 (Neu1) and matrix metalloproteinase-9 (MMP9) crosstalk has been reported in the activation of the insulin receptor (IR) through the modification of the IR glycosylation. Read More

    Coordinated regulation of hepatic FoxO1, PGC-1α and SREBP-1c facilitates insulin action and resistance.
    Cell Signal 2018 Mar 18;43:62-70. Epub 2017 Dec 18.
    Medical and Research Services, James A. Haley Veterans Administration Hospital, Department of Internal Medicine, University of South Florida College of Medicine, Tampa, FL 33704, USA. Electronic address:
    Type 2 diabetes is characterized by insulin resistance, hyperinsulinemia and hepatic overproduction of glucose and lipids. Insulin increases lipogenic enzyme expression by activating Akt and aPKC which activate SREBP-1c; this pathway is hyperactivated in insulin-resistant states. Insulin suppresses gluconeogenic enzyme expression by Akt-dependent phosphorylation/inactivation of FoxO1 and PGC-1α; this pathway is impaired in insulin-resistant states by aPKC excess, which displaces Akt from scaffolding-protein WD40/ProF, where Akt phosphorylates/inhibits FoxO1. Read More

    TGF-β1 up-regulates cadherin-11 expression through Snail: A potential mechanism for human trophoblast cell differentiation.
    Cell Signal 2018 Mar 18;43:55-61. Epub 2017 Dec 18.
    Department of Obstetrics and Gynaecology, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada. Electronic address:
    Cadherins are transmembrane proteins that mediate cell-cell adhesion by promoting the formation of adherens junctions. The regulated expression of cadherins is thought to play important roles in both normal and diseased placental development. Cadherin-11, also known as OB-cadherin, is expressed in human placenta and has been shown to be involved in regulation of trophoblast cell differentiation. Read More

    A shift in the IL-6/STAT3 signalling pathway imbalance towards the SHP2 pathway in severe asthma results in reduced proliferation process.
    Cell Signal 2018 Mar 11;43:47-54. Epub 2017 Dec 11.
    Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Canada. Electronic address:
    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 obtained from severe eosinophilic asthmatics compared to mild asthmatics and healthy controls. Read More

    C60 fullerenes disrupt cellular signalling leading to TRPC4 and TRPC6 channels opening by the activation of muscarinic receptors and G-proteins in small intestinal smooth muscles.
    Cell Signal 2018 Mar 11;43:40-46. Epub 2017 Dec 11.
    A.A. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, 4 Bogomoletz Street, 01024 Kyiv, Ukraine; Taras Shevchenko National University of Kyiv, ESC "Institute of Biology and Medicine", 64 Volodymyrska Street, 01601 Kyiv, Ukraine. Electronic address:
    The effect of water-soluble pristine C60 fullerene nanoparticles (C60NPs) on receptor-operated cation channels formed by TRPC4/C6 proteins in ileal smooth muscle cells was investigated for the first time. Activation of these channels subsequent to acetylcholine binding to the expressed in these cells M2 and M3 muscarinic receptors represents the key event in the parasympathetic control of gastrointestinal smooth muscle motility and cholinergic excitation-contraction coupling. Experiments were performed on single collagenase-dispersed mouse ileal myocytes using patch-clamp techniques with symmetrical 125mM Cs+ solutions and [Ca2+]i 'clamped' at 100nM in order to isolate the muscarinic cation current (mICAT). Read More

    AKT1 distinctively suppresses MyD88-depenedent and TRIF-dependent Toll-like receptor signaling in a kinase activity-independent manner.
    Cell Signal 2018 Mar 11;43:32-39. Epub 2017 Dec 11.
    Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan.
    We found that AKT1, a primary effector molecule of PI3K-AKT signaling, distinctively suppressed Toll-like receptor (TLR)-mediated MyD88-dependent and Toll/IL-1R domain-containing adaptor inducing IFN-β (TRIF)-dependent signaling by inhibiting NF-κB activation and IRF3 activity independently of its kinase activity. In AKT1 knockout RAW264.7 cells, lipopolysaccharide (LPS)-induced transcription and protein production of cytokines including IL-1β and TNF-α (regulated by the MyD88-dependent pathway), as well as IFN-β and RANTES (C-C motif chemokine ligand 5: CCL-5; regulated by the TRIF-dependent pathways) was enhanced compared to wild type cells. Read More

    The mechanism of myocardial hypertrophy regulated by the interaction between mhrt and myocardin.
    Cell Signal 2018 Mar 5;43:11-20. Epub 2017 Dec 5.
    Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan 430065, China. Electronic address:
    As a strong transactivator of promoters containing CarG boxes, myocardin was critical for the cardiac muscle program and necessary for normal cardiogenesis. So it probably represents a viable therapeutic biomarker in the setting of cardiac hypertrophy and failure. In recent years, the studies of regulation of cardiac hypertrophy via myocardin are so common, and the molecular mechanism is becoming more and more clear. Read More

    Phosphorylation of Mig6 negatively regulates the ubiquitination and degradation of EGFR mutants in lung adenocarcinoma cell lines.
    Cell Signal 2018 Mar 2;43:21-31. Epub 2017 Dec 2.
    Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, 138673, Singapore. Electronic address:
    Activating mutations in the kinase domain of epidermal growth factor receptor (EGFR) leads to the constitutively active kinase, improves the EGFR stability and promotes malignant transformation in lung adenocarcinoma. Despite the clinical significance, the mechanism by which the increased kinase activity stabilizes the receptor is not completely understood. Using SILAC phosphoproteomic approach, we identify that Mig6 is highly phosphorylated at S256 in EGFR mutants (19del and L858R). Read More

    TGF-β1/p53 signaling in renal fibrogenesis.
    Cell Signal 2018 Mar 28;43:1-10. Epub 2017 Nov 28.
    Department of Regenerative and Cancer Cell Biology, Albany Medical College, Albany, NY 12208, United States; Department of Surgery, Albany Medical College, Albany, NY 12208, United States; The Urological Institute of Northeastern New York, Albany Medical College, Albany, NY 12208, United States. Electronic address:
    Fibrotic disorders of the renal, pulmonary, cardiac, and hepatic systems are associated with significant morbidity and mortality. Effective therapies to prevent or curtail the advancement to organ failure, however, remain a major clinical challenge. Chronic kidney disease, in particular, constitutes an increasing medical burden affecting >15% of the US population. Read More

    Cyclic nucleotide signaling changes associated with normal aging and age-related diseases of the brain.
    Cell Signal 2018 Jan 23;42:281-291. Epub 2017 Nov 23.
    Department of Pharmacology, Physiology & Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Road, VA Bldg 1, 3rd Floor, D-12, Columbia, SC 29209, United States. Electronic address:
    Deficits in brain function that are associated with aging and age-related diseases benefit very little from currently available therapies, suggesting a better understanding of the underlying molecular mechanisms is needed to develop improved drugs. Here, we review the literature to test the hypothesis that a break down in cyclic nucleotide signaling at the level of synthesis, execution, and/or degradation may contribute to these deficits. A number of findings have been reported in both the human and animal model literature that point to brain region-specific changes in Galphas (a. Read More

    Non-visual arrestins regulate the focal adhesion formation via small GTPases RhoA and Rac1 independently of GPCRs.
    Cell Signal 2018 Jan 11;42:259-269. Epub 2017 Nov 11.
    Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, United States. Electronic address:
    Arrestins recruit a variety of signaling proteins to active phosphorylated G protein-coupled receptors in the plasma membrane and to the cytoskeleton. Loss of arrestins leads to decreased cell migration, altered cell shape, and an increase in focal adhesions. Small GTPases of the Rho family are molecular switches that regulate actin cytoskeleton and affect a variety of dynamic cellular functions including cell migration and cell morphology. Read More

    Cln5 is secreted and functions as a glycoside hydrolase in Dictyostelium.
    Cell Signal 2018 Jan 8;42:236-248. Epub 2017 Nov 8.
    Trent University, Department of Biology, 1600 West Bank Drive, Peterborough, Ontario K9L 0G2, Canada. Electronic address:
    Ceroid lipofuscinosis neuronal 5 (CLN5) is a member of a family of proteins that are linked to neuronal ceroid lipofuscinosis (NCL). This devastating neurological disorder, known commonly as Batten disease, affects all ages and ethnicities and is currently incurable. The precise function of CLN5, like many of the NCL proteins, remains to be elucidated. Read More

    Enhancement of inosine-mediated A2AR signaling through positive allosteric modulation.
    Cell Signal 2018 Jan 8;42:227-235. Epub 2017 Nov 8.
    Molecular Medicine Research Institute, 428 Oakmead Parkway, Sunnyvale, CA 94085.
    Inosine is an endogenous nucleoside that is produced by metabolic deamination of adenosine. Inosine is metabolically more stable (half-life 15h) than adenosine (half-life <10s). Inosine exerts anti-inflammatory and immunomodulatory effects similar to those observed with adenosine. Read More

    Involvement of glucose related energy crisis and endoplasmic reticulum stress: Insinuation of streptozotocin induced Alzheimer's like pathology.
    Cell Signal 2018 Jan 7;42:211-226. Epub 2017 Nov 7.
    Academy of Scientific and Innovative Research (AcSIR), Lucknow 226031, Uttar Pradesh, India. Electronic address:
    The present study was conducted to correlate the cellular and molecular alterations in Alzheimer's pathology employing streptozotocin (STZ) induced experimental rat model. The STZ was administered in rat brain bilaterally by intracerebroventricular route using stereotaxic surgery followed by donepezil dosing. The Alzheimer's related pathological marker like acetylcholinesterase (AChE) activity, tau phosphorylation and amyloid aggregation were observed after STZ administration. Read More

    IL-13 enhances mesenchymal transition of pulmonary artery endothelial cells via down-regulation of miR-424/503 in vitro.
    Cell Signal 2018 Jan 2;42:270-280. Epub 2017 Nov 2.
    Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima 890-8520, Japan.
    Pulmonary arterial hypertension (PAH) has a major effect on life expectancy with functional degeneracy of the lungs and right heart. Interleukin-13 (IL-13), one of the type 2 cytokines mainly associated with allergic diseases, has recently been reported to be associated with Schistosomiasis-associated PAH which shares pathological features with other forms of PAH, such as idiopathic PAH and connective tissue disease-associated PAH. But a direct pathological role of IL-13 in the development of PAH has not been explored. Read More

    Overexpression of dJmj differentially affects intestinal stem cells and differentiated enterocytes.
    Cell Signal 2018 Jan 2;42:194-210. Epub 2017 Nov 2.
    Department of Applied Biology, The Center for Advanced Insect Research, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan. Electronic address:
    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 independent function is suggested for Drosophila Jumonji (dJmj). Read More

    Site-specific O-glycosylation of N-terminal serine residues by polypeptide GalNAc-transferase 2 modulates human δ-opioid receptor turnover at the plasma membrane.
    Cell Signal 2018 Jan 31;42:184-193. Epub 2017 Oct 31.
    Medical Research Center Oulu, Research Unit of Biomedicine, University of Oulu, FI-90014 Oulu, Finland. Electronic address:
    G protein-coupled receptors (GPCRs) are an important protein family of signalling receptors that govern a wide variety of physiological functions. The capacity to transmit extracellular signals and the extent of cellular response are largely determined by the amount of functional receptors at the cell surface that is subject to complex and fine-tuned regulation. Here, we demonstrate that the cell surface expression level of an inhibitory GPCR, the human δ-opioid receptor (hδOR) involved in pain and mood regulation, is modulated by site-specific N-acetylgalactosamine (GalNAc) -type O-glycosylation. Read More

    Blockade of CD38 diminishes lipopolysaccharide-induced macrophage classical activation and acute kidney injury involving NF-κB signaling suppression.
    Cell Signal 2018 Jan 12;42:249-258. Epub 2017 Nov 12.
    Center for Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, PR China. Electronic address:
    The CD38, possessing ADP-ribosyl cyclase (ADPR-cyclase) and cyclic ADP-ribose hydrolase (cADPR-hydrolase), is able to regulate a variety of cellular activities. However, the role and mechanisms for CD38 in macrophage activation and sepsis-induced acute kidney injury (AKI) remain to be determined. Here we report that in cultured macrophages, Lipopolysaccharide (LPS) could upregulate CD38 expression in time and dose dependent manner. Read More

    Optogenetic control of focal adhesion kinase signaling.
    Cell Signal 2018 Jan 23;42:176-183. Epub 2017 Oct 23.
    Faculty of Biology, University of Freiburg, Schaenzlestr. 1, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, Schaenzlestr. 18, 79104 Freiburg, Germany. Electronic address:
    Focal adhesion kinase (FAK) integrates signaling from integrins, growth factor receptors and mechanical stress to control cell adhesion, motility, survival and proliferation. Here, we developed a single-component, photo-activatable FAK, termed optoFAK, by using blue light-induced oligomerization of cryptochrome 2 (CRY2) to activate FAK-CRY2 fusion proteins. OptoFAK functions uncoupled from physiological stimuli and activates downstream signaling rapidly and reversibly upon blue light exposure. Read More

    Uev1A-Ubc13 catalyzes K63-linked ubiquitination of RHBDF2 to promote TACE maturation.
    Cell Signal 2018 Jan 22;42:155-164. Epub 2017 Oct 22.
    Beijing Key Laboratory of DNA Damage Responses and College of Life Sciences, Capital Normal University, Beijing 100048, China; Department of Microbiology and Immunology, University of Saskatchewan, S7N 5E5, Canada. Electronic address:
    The TNFα-induced NF-κB signaling pathway plays critical roles in multiple biological processes. Extensive studies have explored the mechanisms regulating this signaling cascade, and identified an E2 complex, Uev1A-Ubc13, that mediates K63-linked poly-Ub chain formation and thus recruits NEMO to activate the signaling transduction. In this study, we demonstrate that the Uev1A-Ubc13 complex simultaneously serves as a repressor of the NF-κB pathway. Read More

    Emerging role of non-coding RNA in oral cancer.
    Cell Signal 2018 Jan 19;42:134-143. Epub 2017 Oct 19.
    Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address:
    Oral squamous cell carcinoma (OSCC) is characterized by genomic and epigenomic alterations. However, the mechanisms underlying oral squamous cell carcinoma tumorigenesis and progression remain to be elucidated. Long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and extracellular RNAs (exRNAs) are emerging groups of regulatory RNAs, which possess low or no protein-coding potential. Read More

    The allosteric site regulates the voltage sensitivity of muscarinic receptors.
    Cell Signal 2018 Jan 19;42:114-126. Epub 2017 Oct 19.
    Department of Cardiovascular Physiology, Ruhr-University Bochum, Universitätsstr. 150, 44780 Bochum, Germany. Electronic address:
    Muscarinic receptors (M-Rs) for acetylcholine (ACh) belong to the class A of G protein-coupled receptors. M-Rs are activated by orthosteric agonists that bind to a specific site buried in the M-R transmembrane helix bundle. In the active conformation, receptor function can be modulated either by allosteric modulators, which bind to the extracellular receptor surface or by the membrane potential via an unknown mechanism. Read More

    Rac1 plays a role in CXCL12 but not CCL3-induced chemotaxis and Rac1 GEF inhibitor NSC23766 has off target effects on CXCR4.
    Cell Signal 2018 Jan 16;42:88-96. Epub 2017 Oct 16.
    School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK. Electronic address:
    Cell migration towards a chemotactic stimulus relies on the re-arrangement of the cytoskeleton, which is triggered by activation of small G proteins RhoA, Rac1 and Cdc42, and leads to formation of lamellopodia and actin polymerisation amongst other effects. Here we show that Rac1 is important for CXCR4 induced chemotaxis but not for CCR1/CCR5 induced chemotaxis. For CXCL12-induced migration via CXCR4, breast cancer MCF-7 cells are reliant on Rac1, similarly to THP-1 monocytes and Jurkat T-cells. Read More

    Bromodomain protein BRD4 promotes cell proliferation in skin squamous cell carcinoma.
    Cell Signal 2018 Jan 16;42:106-113. Epub 2017 Oct 16.
    Department of Plastic Surgery, the Second Affiliated Hospital of Suzhou University, Suzhou, China. Electronic address:
    The present study examined the expression and biological functions of bromodomain-containing protein 4 (BRD4) in skin squamous cell carcinoma (SCC) cells. Our results show that BRD4 mRNA and protein expression was upregulated in human skin SCC cells, as compared to its level in the normal skin keratinocytes and fibroblasts. Treatment with BRD4 inhibitors, JQ1 and CPI203, resulted in proliferation inhibition, apoptosis and cell cycle arrest in both established (A431 cell line) and primary skin SCC cells. Read More

    Protein kinase- and lipase inhibitors of inositide metabolism deplete IP7 indirectly in pancreatic β-cells: Off-target effects on cellular bioenergetics and direct effects on IP6K activity.
    Cell Signal 2018 Jan 16;42:127-133. Epub 2017 Oct 16.
    The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, SE-171 76 Stockholm, Sweden. Electronic address:
    Inositol pyrophosphates have emerged as important regulators of many critical cellular processes from vesicle trafficking and cytoskeletal rearrangement to telomere length regulation and apoptosis. We have previously demonstrated that 5-di-phosphoinositol pentakisphosphate, IP7, is at a high level in pancreatic β-cells and is important for insulin exocytosis. To better understand IP7 regulation in β-cells, we used an insulin secreting cell line, HIT-T15, to screen a number of different pharmacological inhibitors of inositide metabolism for their impact on cellular IP7. Read More

    Regulating the regulators: Epigenetic, transcriptional, and post-translational regulation of RGS proteins.
    Cell Signal 2018 Jan 16;42:77-87. Epub 2017 Oct 16.
    Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA, USA. Electronic address:
    Regulators of G protein signaling (RGS) are a family of proteins classically known to accelerate the intrinsic GTPase activity of G proteins, which results in accelerated inactivation of heterotrimeric G proteins and inhibition of G protein coupled receptor signaling. RGS proteins play major roles in essential cellular processes, and dysregulation of RGS protein expression is implicated in multiple diseases, including cancer, cardiovascular and neurodegenerative diseases. The expression of RGS proteins is highly dynamic and is regulated by epigenetic, transcriptional and post-translational mechanisms. Read More

    Impairment of energy sensors, SIRT1 and AMPK, in lipid induced inflamed adipocyte is regulated by Fetuin A.
    Cell Signal 2018 Jan 10;42:67-76. Epub 2017 Oct 10.
    Cellular and Molecular Endocrinology Laboratory, Centre for Advanced Studies in Zoology, School of Life Science, Visva-Bharati (A Central University), Santiniketan, India. Electronic address:
    Although several reports demonstrated that accumulation of excess lipid in adipose tissue produces defects in adipocyte which leads to the disruption of energy homeostasis causing severe metabolic problems, underlying mechanism of this event remains yet unclear. Here we demonstrate that FetuinA (FetA) plays a critical role in the impairment of two metabolic sensors, SIRT1 and AMPK, in inflamed adipocytes of high fat diet (HFD) mice. A linear increase in adipocyte hypertrophy from 10 to 16 week was in tandem with the increase in FetA and that coincided with SIRT1 cleavage and decrease in pAMPK which adversely affects PGC1α activation. Read More

    Proteomic analyses of signalling complexes associated with receptor tyrosine kinase identify novel members of fibroblast growth factor receptor 3 interactome.
    Cell Signal 2018 Jan 13;42:144-154. Epub 2017 Oct 13.
    Department of Biology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic; Department of Human Genetics and Orthopaedic Surgery, University of California Los Angeles, California 90095, USA. Electronic address:
    Receptor tyrosine kinases (RTKs) form multiprotein complexes that initiate and propagate intracellular signals and determine the RTK-specific signalling patterns. Unravelling the full complexity of protein interactions within the RTK-associated complexes is essential for understanding of RTK functions, yet it remains an understudied area of cell biology. We describe a comprehensive approach to characterize RTK interactome. Read More

    Tubulin-dependent secretion of S100A6 and cellular signaling pathways activated by S100A6-integrin β1 interaction.
    Cell Signal 2018 Jan 8;42:21-29. Epub 2017 Oct 8.
    Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, Poland. Electronic address:
    S100A6 is a calcium binding protein expressed mainly in fibroblasts and epithelial cells. Interestingly, S100A6 is also present in extracellular fluids. Recently we have shown that S100A6 is secreted by WJMS cells and binds to integrin β1 (Jurewicz et al. Read More

    KiSS1 gene as a novel mediator of TGFβ-mediated cell invasion in triple negative breast cancer.
    Cell Signal 2018 Jan 6;42:1-10. Epub 2017 Oct 6.
    Department of Medicine, McGill University Health Center, Cancer Research Program, Montreal, QC, H4A 3J1, Canada. Electronic address:
    The invasive and metastatic phenotypes of breast cancer correlate with high recurrence rates and poor survival outcomes. Transforming growth factor-β (TGFβ) promotes tumor progression and metastasis in aggressive breast cancer. Here, we identified the kisspeptin KiSS1 as a downstream target of canonical TGFβ/Smad2 pathway in triple negative breast cancer cells. Read More

    KLF4 overcomes tamoxifen resistance by suppressing MAPK signaling pathway and predicts good prognosis in breast cancer.
    Cell Signal 2018 Jan 4;42:165-175. Epub 2017 Oct 4.
    Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, China. Electronic address:
    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, we examined the clinical significance and biologic effects of KLF4 in breast cancer. Read More

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