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    4539 results match your criteria Cellular Signalling [Journal]

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    GPCRs: Emerging anti-cancer drug targets.
    Cell Signal 2017 Sep 17. Epub 2017 Sep 17.
    The Scripps Research Institute, Department of Molecular Medicine, 130 Scripps Way, Jupiter, FL 33458, United States. Electronic address:
    G protein-coupled receptors (GPCRs) constitute the largest and most diverse protein family in the human genome with over 800 members identified to date. They play critical roles in numerous cellular and physiological processes, including cell proliferation, differentiation, neurotransmission, development and apoptosis. Consequently, aberrant receptor activity has been demonstrated in numerous disorders/diseases, and as a result GPCRs have become the most successful drug target class in pharmaceuticals treating a wide variety of indications such as pain, inflammation, neurobiological and metabolic disorders. Read More

    The role of A-kinase anchoring proteins in cancer development.
    Cell Signal 2017 Sep 16. Epub 2017 Sep 16.
    Département de Pharmacologie et de Toxicologie, Faculté de Biologie et de Médecine, Lausanne 1005, Switzerland.. Electronic address:
    Cancer development is a multifactorial process resulting from the aberrant activation of multiple signaling pathways. It has become increasingly clear that the coordination of the signaling events leading to cancer formation and progression is under the control of macromolecular transduction complexes organized by scaffolding proteins. A-kinase anchoring proteins (AKAPs) constitute a family of scaffolding proteins involved in the spatio-temporal activation of pathways controlling cancer cell proliferation, cell survival, and invasion. Read More

    FGD5 sustains vascular endothelial growth factor A (VEGFA) signaling through inhibition of proteasome-mediated VEGF receptor 2 degradation.
    Cell Signal 2017 Sep 16. Epub 2017 Sep 16.
    Dept. of Medical Cell Biology, Uppsala University, Uppsala, Sweden. Electronic address:
    The complete repertoire of endothelial functions elicited by FGD5, a guanine nucleotide exchange factor activating the Rho GTPase Cdc42, has yet to be elucidated. Here we explore FGD5's importance during vascular endothelial growth factor A (VEGFA) signaling via VEGF receptor 2 (VEGFR2) in human endothelial cells. In microvascular endothelial cells, FGD5 is located at the inner surface of the cell membrane as well as at the outer surface of EEA1-positive endosomes carrying VEGFR2. Read More

    The C1 domain of Vav3, a novel potential therapeutic target.
    Cell Signal 2017 Sep 16. Epub 2017 Sep 16.
    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address:
    Vav1/2/3 comprise a protein family with guanyl nucleotide exchange activity for Rho and Rac as well as with motifs conferring adapter activity. Biologically, Vav1 plays a critical role in hematologic cell signaling, whereas Vav2/3 have a wider tissue distribution, but all 3 Vav proteins are implicated in cancer development. A structural feature of Vav1/2/3 is the presence of an atypical C1 domain, which possesses close structural homology to the typical C1 domains of protein kinase C but which fails to bind the second messenger diacylglycerol or the potent analogs, the phorbol esters. Read More

    Cocaine modulates allosteric D2-σ1 receptor-receptor interactions on dopamine and glutamate nerve terminals from rat striatum.
    Cell Signal 2017 Sep 18;40:116-124. Epub 2017 Sep 18.
    Department of Life Sciences and Biotechnology (SVEB), University of Ferrara, Ferrara, Italy. Electronic address:
    The effects of nanomolar cocaine concentrations, possibly not blocking the dopamine transporter activity, on striatal D2-σ1 heteroreceptor complexes and their inhibitory signaling over Gi/o, have been tested in rat striatal synaptosomes and HEK293T cells. Furthermore, the possible role of σ1 receptors (σ1Rs) in the cocaine-provoked amplification of D2 receptor (D2R)-induced reduction of K(+)-evoked [(3)H]-DA and glutamate release from rat striatal synaptosomes, has also been investigated. The dopamine D2-likeR agonist quinpirole (10nM-1μM), concentration-dependently reduced K(+)-evoked [(3)H]-DA and glutamate release from rat striatal synaptosomes. Read More

    Diindolylmethane and its halogenated derivatives induce protective autophagy in human prostate cancer cells via induction of the oncogenic protein AEG-1 and activation of AMP-dependent kinase (AMPK).
    Cell Signal 2017 Sep 15. Epub 2017 Sep 15.
    INRS-Institut Armand-Frappier, Laval, QC, Canada. Electronic address:
    3,3'-Diindolylmethane (DIM) and its synthetic halogenated derivatives 4,4'-Br2- and 7,7'-Cl2DIM (ring-DIMs) have recently been shown to induce protective autophagy in human prostate cancer cells. The mechanisms by which DIM and ring-DIMs induce autophagy have not been elucidated. As DIM is a mitochondrial ATP-synthase inhibitor, we hypothesized that DIM and ring-DIMs induce autophagy via alteration of intracellular AMP/ATP ratios and activation of AMPK signaling in prostate cancer cells. Read More

    Glucose elicits serine/threonine kinase VRK1 to phosphorylate nuclear pregnane X receptor as a novel hepatic gluconeogenic signal.
    Cell Signal 2017 Sep 11. Epub 2017 Sep 11.
    Pharmacogenetics Section, Reproductive and Developmental Biology Laboratory, National Institute of Environmental Sciences, National Institutes of Health, Research Triangle Park, NC 27709, United States. Electronic address:
    Low glucose stimulated phosphorylation of pregnane X receptor (PXR) at Ser(350) in correlation with an increased gluconeogenesis in human hepatoma-derived HepG2 cells. Only glucose, but neither insulin nor glucagon, stimulated this phosphorylation. Here, serine/threonine kinase, vaccinia related kinase 1 (VRK1)-mediated phosphorylation of PXR is now defined as this glucose-elicited novel signal. Read More

    Recent development of signaling pathways inhibitors of melanogenesis.
    Cell Signal 2017 Sep 12;40:99-115. Epub 2017 Sep 12.
    College of Pharmacy and Institute of Drug Research and Development, Chungnam National, University, Daejeon 34134, Republic of Korea.
    Human skin, eye and hair color rely on the production of melanin, depending on its quantity, quality, and distribution, Melanin plays a monumental role in protecting the skin against the harmful effect of ultraviolet radiation and oxidative stress from various environmental pollutants. However, an excessive production of melanin causes serious dermatological problems such as freckles, solar lentigo (age spots), melasma, as well as cancer. Hence, the regulation of melanin production is important for controlling the hyper-pigmentation. Read More

    Fibroblast-derived HGF drives acinar lung cancer cell polarization through integrin-dependent RhoA-ROCK1 inhibition.
    Cell Signal 2017 Sep 6;40:91-98. Epub 2017 Sep 6.
    Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, United Kingdom; The CRUK Beatson Institute, Glasgow G61 1BD, United Kingdom. Electronic address:
    The formation of lumens in epithelial tissues requires apical-basal polarization of cells, and the co-ordination of this individual polarity collectively around a contiguous lumen. Signals from the Extracellular Matrix (ECM) instruct epithelia as to the orientation of where basal, and thus consequently apical, surfaces should be formed. We report that this pathway is normally absent in Calu-3 human lung adenocarcinoma cells in 3-Dimensional culture, but that paracrine signals from MRC5 lung fibroblasts can induce correct orientation of polarity and acinar morphogenesis. Read More

    MAPK activation patterns of AT1R and CB1R in SHR versus Wistar astrocytes: Evidence of CB1R hypofunction and crosstalk between AT1R and CB1R.
    Cell Signal 2017 Sep 5;40:81-90. Epub 2017 Sep 5.
    Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, United States. Electronic address:
    Background: Angiotensin (Ang) II and cannabinoids regulate physiologically relevant astroglial functions via receptor-mediated activation of Mitogen-activated protein kinases (MAPKs). In this study, we investigated the consequences of astroglial Ang II type 1 receptor (AT1R) and Cannabinoid type 1 receptor (CB1R) activation, alone and in combination, on MAPK activation in the presence and absence of hypertensive states. In addition, we also investigated a novel unidirectional crosstalk mechanism between AT1R and CB1R, that involves PKC-mediated phosphorylation of CB1R. Read More

    t-Darpp stimulates protein kinase A activity by forming a complex with its RI regulatory subunit.
    Cell Signal 2017 Sep 1;40:53-61. Epub 2017 Sep 1.
    Department of Cancer Biology, City of Hope, 1500 East Duarte Road, Duarte, CA 91107, USA. Electronic address:
    t-Darpp is the truncated form of the dopamine- and cAMP-regulated phosphoprotein of 32kDa (Darpp-32) and has been demonstrated to confer resistance to trastuzumab, a Her2-targeted anticancer agent, via sustained signaling through the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt pathway and activation of protein kinase A (PKA). The mechanism of t-Darpp-mediated PKA activation is poorly understood. In the PKA holoenzyme, when the catalytic subunits are bound to regulatory subunits RI or RII, kinase activity is inhibited. Read More

    Identification and characterization of a potent and biologically-active PDE4/7 inhibitor via fission yeast-based assays.
    Cell Signal 2017 Sep 1;40:73-80. Epub 2017 Sep 1.
    Biology Department, Boston College, 140 Commonwealth Ave., Chestnut Hill, MA 02467, USA. Electronic address:
    We previously constructed a collection of fission yeast strains that express various mammalian cyclic nucleotide phosphodiesterases (PDEs) and developed a cell-based high throughput screen (HTS) for small molecule PDE inhibitors. Here we describe a compound, BC54, that is a selective inhibitor of enzymes from the cAMP-specific PDE4 and PDE7 families. Consistent with the biological effect of other PDE4 and PDE7 inhibitors, BC54 displays potent anti-inflammatory properties and is superior to a combination of rolipram (a PDE4 inhibitor) and BRL50481 (a PDE7A inhibitor) for inducing apoptosis in chronic lymphocytic leukemia (CLL) cells. Read More

    Store-operated calcium entry is dispensable for the activation of ERK1/2 pathway in prostate cancer cells.
    Cell Signal 2017 Aug 31;40:44-52. Epub 2017 Aug 31.
    Department of Cell Biology, School of Medicine and Institute of Molecular Pathology and Biomarkers, University of Extremadura, Badajoz 06006, Spain. Electronic address:
    STIM1, the endoplasmic reticulum Ca(2+) sensor that modulates the activity of plasma membrane Ca(2+) channels, becomes phosphorylated at ERK1/2 target sites during Ca(2+) store depletion triggered by thapsigargin or epidermal growth factor (EGF). This ERK1/2-dependent phosphorylation regulates STIM1 localization and dissociation from microtubules, and it is known that enhances the binding to ORAI1, a store-operated Ca(2+) entry (SOCE) channel, leading to the activation of this Ca(2+) influx pathway. However, there remained some evidence of a role for SOCE in the activation of ERK1/2, and here we assessed the contribution of SOCE to ERK1/2 activation by generating a STIM1-deficient cell line by CRISPR/Cas9 genome editing of the STIM1 locus in prostate cancer PC3 cells. Read More

    PDE8 controls CD4(+) T cell motility through the PDE8A-Raf-1 kinase signaling complex.
    Cell Signal 2017 Aug 26;40:62-72. Epub 2017 Aug 26.
    Department of Immunology, UConn Health, United States. Electronic address:
    The levels of cAMP are regulated by phosphodiesterase enzymes (PDEs), which are targets for the treatment of inflammatory disorders. We have previously shown that PDE8 regulates T cell motility. Here, for the first time, we report that PDE8A exerts part of its control of T cell function through the V-raf-1 murine leukemia viral oncogene homolog 1 (Raf-1) kinase signaling pathway. Read More

    Complexity of the Wnt/β‑catenin pathway: Searching for an activation model.
    Cell Signal 2017 Aug 26;40:30-43. Epub 2017 Aug 26.
    Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address:
    Wnt signaling refers to a conserved signaling pathway, widely studied due to its roles in cellular communication, cell fate decisions, development and cancer. However, the exact mechanism underlying inhibition of the GSK phosphorylation towards β-catenin and activation of the pathway after biding of Wnt ligand to its cognate receptors at the plasma membrane remains unclear. Wnt target genes are widely spread over several animal phyla. Read More

    Integrated stress response stimulates FGF21 expression: Systemic enhancer of longevity.
    Cell Signal 2017 Aug 24;40:10-21. Epub 2017 Aug 24.
    School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
    FGF21 is a multifunctional metabolic and stress hormone which is normally expressed in liver but cellular stress, e.g. mitochondrial or endoplasmic reticulum (ER) stress, can induce its expression and subsequent secretion from several mammalian tissues. Read More

    NGF protects endothelial cells from indomethacin-induced injury through activation of mitochondria and upregulation of IGF-1.
    Cell Signal 2017 Aug 24;40:22-29. Epub 2017 Aug 24.
    Medical and Research Services, Veterans Affairs Long Beach Healthcare System (VALBHS), Long Beach, CA, USA; Department of Medicine, University of California, Irvine, CA, USA. Electronic address:
    Background/aims: Endothelial cells (ECs) lining blood vessels are critical for delivery of oxygen and nutrients to all tissues and organs and play a crucial role in the regeneration of blood vessel following tissue injury. ECs are also major targets of injury by a variety of noxious factors [e.g. Read More

    Protein kinase C isoforms in the normal pancreas and in pancreatic disease.
    Cell Signal 2017 Aug 18;40:1-9. Epub 2017 Aug 18.
    Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA. Electronic address:
    Protein Kinase C isoforms have been implicated in regulating multiple processes within the healthy pancreas. Moreover, their dysregulation contributes to all aspects of pancreatic disease. In this review, with a focus on acinar, ductal, and islet cells, we highlight the roles and contributions of the different PKC isoforms to normal pancreas function. Read More

    In situ detection of the activation of Rac1 and RalA small GTPases in mouse adipocytes by immunofluorescent microscopy following in vivo and ex vivo insulin stimulation.
    Cell Signal 2017 Nov 15;39:108-117. Epub 2017 Aug 15.
    Laboratory of Cell Biology, Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai 599-8531, Japan. Electronic address:
    Rac1 has been implicated in insulin-dependent glucose uptake by mechanisms involving plasma membrane translocation of the glucose transporter GLUT4 in skeletal muscle. Although the uptake of glucose is also stimulated by insulin in adipose tissue, the role for Rac1 in adipocyte insulin signaling remains controversial. As a step to reveal the role for Rac1 in adipocytes, we aimed to establish immunofluorescent microscopy to detect the intracellular distribution of activated Rac1. Read More

    Apelin protects against liver X receptor-mediated steatosis through AMPK and PPARα in human and mouse hepatocytes.
    Cell Signal 2017 Nov 15;39:84-94. Epub 2017 Aug 15.
    Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea. Electronic address:
    Non-alcoholic fatty liver disease is the most commonly occurring chronic liver disease, and hepatic steatosis, a condition defined as extensive lipid accumulation in hepatocytes, is associated with liver dysfunction and metabolic diseases, such as, obesity and type II diabetes. Apelin is an adipokine that acts on a G protein-coupled receptor named APJ, and has been established to play pivotal roles in various physiological conditions. However, the function of apelin in hepatocytes has not been fully investigated. Read More

    The role of G protein-coupled receptors in lymphoid malignancies.
    Cell Signal 2017 Nov 9;39:95-107. Epub 2017 Aug 9.
    National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA. Electronic address:
    B cell lymphoma consists of multiple individual diseases arising throughout the lifespan of B cell development. From pro-B cells in the bone marrow, through circulating mature memory B cells, each stage of B cell development is prone to oncogenic mutation and transformation, which can lead to a corresponding lymphoma. Therapies designed against individual types of lymphoma often target features that differ between malignant cells and the corresponding normal cells from which they arise. Read More

    CDK1-mediated mitotic phosphorylation of PBK is involved in cytokinesis and inhibits its oncogenic activity.
    Cell Signal 2017 Nov 3;39:74-83. Epub 2017 Aug 3.
    Eppley Institute for Research in Cancer, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, United States; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, United States; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, United States. Electronic address:
    PDZ-binding kinase (PBK) plays a major role in proliferation and in safeguarding mitotic fidelity in cancer cells. Frequently upregulated in many cancers, PBK drives tumorigenesis and metastasis. PBK has been shown to be phosphorylated in mitosis by cyclin-dependent kinase 1 (CDK1)/cyclin B, however, no studies have been done examining PBK mitotic phosphorylation in oncogenesis. Read More

    15-Lipoxygenase-1 re-expression in colorectal cancer alters endothelial cell features through enhanced expression of TSP-1 and ICAM-1.
    Cell Signal 2017 Nov 28;39:44-54. Epub 2017 Jul 28.
    Department of Biological Sciences, Orta Dogu Teknik Universitesi (ODTU/METU), Ankara 06800, Turkey. Electronic address:
    15-lipoxygenase-1 (15-LOX-1) oxygenates linoleic acid to 13(S)-hydroxyoctadecadienoic acid (HODE). The enzyme is widely suppressed in different cancers and its re-expression has tumor suppressive effects. 15-LOX-1 has been shown to inhibit neoangiogenesis in colorectal cancer (CRC); in the present study we confirm this phenomenon and describe the mechanistic basis. Read More

    Stress-induced hyperacetylation of microtubule enhances mitochondrial fission and modulates the phosphorylation of Drp1 at (616)Ser.
    Cell Signal 2017 Nov 28;39:32-43. Epub 2017 Jul 28.
    Univ. Paris-Sud, INSERM UMR-S 1193, Université Paris-Saclay, Faculté de Pharmacie, Châtenay-Malabry, France; Biochimie-Hormonologie, APHP, Hôpitaux Universitaires Paris-Sud, Site Antoine Béclère, Clamart, France.
    Mitochondria dynamics results from fission and fusion events that may be unbalanced in favor of mitochondrial fragmentation upon cell stress. During oxidative stress, microtubules are hyperacetylated in a mitochondria-dependent manner. In this study, we show that under stress conditions, most of the mitochondria form foci with microtubule domains that carry Drp1. Read More

    Osmotic and heat stress-dependent regulation of MLK4β and MLK3 by the CHIP E3 ligase in ovarian cancer cells.
    Cell Signal 2017 Nov 28;39:66-73. Epub 2017 Jul 28.
    Department of Biological Sciences, The University of Toledo, Toledo, OH 43606, USA. Electronic address:
    Mixed Lineage Kinase 3 (MLK3), a member of the MLK subfamily of protein kinases, is a mitogen-activated protein (MAP) kinase kinase kinase (MAP3K) that activates MAPK signalling pathways and regulates cellular responses such as proliferation, invasion and apoptosis. MLK4β, another member of the MLK subfamily, is less extensively studied, and the regulation of MLK4β by stress stimuli is not known. In this study, the regulation of MLK4β and MLK3 by osmotic stress, thermostress and heat shock protein 90 (Hsp90) inhibition was investigated in ovarian cancer cells. Read More

    Therapeutic potentials of natural compounds acting on cyclic nucleotide phosphodiesterase families.
    Cell Signal 2017 Nov 25;39:55-65. Epub 2017 Jul 25.
    UMR 7213, Université de Strasbourg, France. Electronic address:
    Intracellular cyclic AMP and/or cyclic GMP are characterized in the 1960th. These second messengers, hydrolysed specifically by cyclic nucleotide phosphodiesterase (PDE), play a major role in intracellular signalling. Natural products have been a rich source of drug discovery, Theophylline and Methylxanthine originated from tea leaves used for asthma treatment, whereas, Papaverine, a natural isoquinolein originated from Papaver somniferum traditionally used in impotency, altogether as caffeine where firstly described as PDE-inhibiting compounds. Read More

    The extracellular role of DNA damage repair protein APE1 in regulation of IL-6 expression.
    Cell Signal 2017 Nov 25;39:18-31. Epub 2017 Jul 25.
    Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA; Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA. Electronic address:
    The human apurinic/apyrimidinic endonuclease 1 (APE1) is a pleiotropic nuclear protein with roles in DNA base excision repair pathway as well as in regulation of transcription. Recently, the presence of extracellular plasma APE1 was reported in endotoxemic rats. However, the biological significance and the extracellular function of APE1 remain unclear. Read More

    Corrigendum to "Palmitoylation of the TPβ isoform of the human thromboxane A2 receptor. Modulation of G protein: Effector coupling and modes of receptor internalization." [Cell Signal. 19(5) (2007) 1056-1070].
    Cell Signal 2017 Oct 25;38:238. Epub 2017 Jul 25.
    School of Biomolecular and Biomedical Sciences, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland. Electronic address:

    Pyruvate kinase M1 interacts with A-Raf and inhibits endoplasmic reticulum stress-induced apoptosis by activating MEK1/ERK pathway in mouse insulinoma cells.
    Cell Signal 2017 Oct 22;38:212-222. Epub 2017 Jul 22.
    Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan; Cell Biology Unit, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsutacho, Midori-ku, Yokohama, Kanagawa 226-8503, Japan. Electronic address:
    Apoptotic death of pancreatic β cells is a major cause of type 2 diabetes mellitus (T2D) progression. Two isoforms of pyruvate kinase, PKM1 and PKM2, have been reported to participate in cell death in several cell types; however, little is known about their causal pathways in pancreatic β-cell death. We examined whether the suppression of PKM1 or PKM2 affects endoplasmic reticulum (ER) stress-induced apoptosis in a pancreatic β-cell line, MIN6, and Beta-TC-6 and found that knockdown of PKM1, but not of PKM2, leads to the induction of ER stress-induced apoptosis in these cells. Read More

    MicroRNA-146a-5p attenuates liver fibrosis by suppressing profibrogenic effects of TGFβ1 and lipopolysaccharide.
    Cell Signal 2017 Nov 21;39:1-8. Epub 2017 Jul 21.
    Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai, PR China. Electronic address:
    Liver fibrosis is characterized by proliferation and activation of hepatic stellate cells (HSCs). Transforming growth factor-β1 (TGFβ1) is crucial for liver fibrogenesis, and gut-derived endotoxin (LPS) also plays an important role in liver fibrogenesis. In the present study, we found that microRNA-146a-5p (miR-146a-5p) could regulate TGFβ1/Smad and LPS/NF-κB/Bambi pathways to attenuate liver fibrosis. Read More

    HSP90 is necessary for the ACK1-dependent phosphorylation of STAT1 and STAT3.
    Cell Signal 2017 Nov 21;39:9-17. Epub 2017 Jul 21.
    Department of Toxicology, University Medical Center, Obere Zahlbacher Str. 67, 55131 Mainz, Germany. Electronic address:
    Signal transducers and activators of transcription (STATs) are latent, cytoplasmic transcription factors. Janus kinases (JAKs) and activated CDC42-associated kinase-1 (ACK1/TNK2) catalyse the phosphorylation of STAT1 and the expression of its target genes. Here we demonstrate that catalytically active ACK1 promotes the phosphorylation and nuclear accumulation of STAT1 in transformed kidney cells. Read More

    Protein kinase Cι/λ is dispensable for platelet function in thrombosis and hemostasis in mice.
    Cell Signal 2017 Oct 21;38:223-229. Epub 2017 Jul 21.
    Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany. Electronic address:
    Platelet activation at sites of vascular injury is crucial for hemostasis, but it may also cause myocardial infarction or ischemic stroke. Upon platelet activation, cytoskeletal reorganization is essential for platelet secretion and thrombus formation. Members of the protein kinase C family, which includes 12 isoforms, are involved in most platelet responses required for thrombus formation. Read More

    Selenium deficiency-induced thioredoxin suppression and thioredoxin knock down disbalanced insulin responsiveness in chicken cardiomyocytes through PI3K/Akt pathway inhibition.
    Cell Signal 2017 Oct 19;38:192-200. Epub 2017 Jul 19.
    College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China. Electronic address:
    Thioredoxin (Txn) system is the most crucial antioxidant defense mechanism in cell consisting of Txn, thioredoxin reductase (TR) and Nicotinamide Adenine Dinucleotide Phosphate (NADPH). Perturbations in Txn system may compromise cell survival through oxidative stress induction. Metabolic activity of insulin plays important roles in fulfilling the stable and persistent demands of heart through glucose metabolism. Read More

    Functional consequences of chemically-induced β-arrestin binding to chemokine receptors CXCR4 and CCR5 in the absence of ligand stimulation.
    Cell Signal 2017 Oct 18;38:201-211. Epub 2017 Jul 18.
    Department of Cellular and Molecular Immunology, University of Göttingen, Göttingen, Niedersachsen, Germany.
    Chemokine receptor signaling is a tightly regulated process which was for a long time exclusively attributed to heterotrimeric G proteins. β-Arrestins constitute a separable signaling arm from classical heterotrimeric G proteins, in addition to their well-established roles in receptor desensitization and endocytosis. In order to clearly dissect β-arrestin- from G protein-dependent effects we forced the recruitment of β-arrestin to CXCR4 and CCR5 independently of agonist-promoted receptor activation through chemically-induced dimerization. Read More

    Reciprocal regulation of β2-adrenoceptor-activated cAMP response-element binding protein signalling by arrestin2 and arrestin3.
    Cell Signal 2017 Oct 18;38:182-191. Epub 2017 Jul 18.
    Department of Molecular Cell Biology, University of Leicester, Henry Wellcome Building, Lancaster, Road Leicester, LE1 9HN, United Kingdom. Electronic address:
    Activation of Gs coupled receptors (e.g. β2-adrenoreceptor (β2AR)) expressed within the uterine muscle layer (myometrium), promotes intracellular cAMP generation, inducing muscle relaxation through short-term inhibition of contractile proteins, and longer-term modulation of cellular phenotype to promote quiescence. Read More

    Advances and challenges in the search for D2 and D3 dopamine receptor-selective compounds.
    Cell Signal 2017 Jul 14. Epub 2017 Jul 14.
    Molecular Neuropharmacology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, MSC-3723, Bethesda, MD 20892-3723, United States. Electronic address:
    Compounds that target D2-like dopamine receptors (DRs) are currently used as therapeutics for several neuropsychiatric disorders including schizophrenia (antagonists) and Parkinson's disease (agonists). However, as the D2R and D3R subtypes are highly homologous, creating compounds with sufficient subtype-selectivity as well as drug-like properties for therapeutic use has proved challenging. This review summarizes the progress that has been made in developing D2R- or D3R-selective antagonists and agonists, and also describes the experimental conditions that need to be considered when determining the selectivity of a given compound, as apparent selectivity can vary widely depending on assay conditions. Read More

    G protein-coupled receptor kinases: Past, present and future.
    Cell Signal 2017 Jul 12. Epub 2017 Jul 12.
    Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107, United States. Electronic address:
    This review is provided in recognition of the extensive contributions of Dr. Robert J. Lefkowitz to the G protein-coupled receptor (GPCR) field and to celebrate his 75th birthday. Read More

    Phospholipase D1 is a regulator of platelet-mediated inflammation.
    Cell Signal 2017 Oct 12;38:171-181. Epub 2017 Jul 12.
    Department of Vascular and Endovascular Surgery, Heinrich-Heine University Medical Center, Düsseldorf, Germany. Electronic address:
    Glycoprotein (GP)Ib is not only required for stable thrombus formation but for platelet-mediated inflammatory responses. Phospholipase (PL)D1 is essential for GPIb-dependent aggregate formation under high shear conditions while nothing is known about PLD1-induced regulation of GPIb in platelet-mediated inflammation and the underlying mechanisms. This study aimed to investigate the relevance of PLD1 for platelet-mediated endothelial and leukocyte recruitment and activation in vitro and in vivo. Read More

    Phosphatidylinositol 4-phosphate 5-kinase α contributes to Toll-like receptor 2-mediated immune responses in microglial cells stimulated with lipoteichoic acid.
    Cell Signal 2017 Oct 13;38:159-170. Epub 2017 Jul 13.
    Department of Biomedical Sciences, Neuroscience Graduate Program, Ajou University School of Medicine, Suwon, Gyeonggi 443-721, South Korea; Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, Gyeonggi 443-721, South Korea. Electronic address:
    Phosphatidylinositol 4,5-bisphosphate (PIP2) is an important lipid regulator of membrane signaling and remodeling processes. Accumulating evidence indicates a link between PIP2 metabolism and Toll-like receptor (TLR) signaling, a key transducer of immune responses such as inflammation, phagocytosis, and autophagy. Microglia are immune effector cells that serve as macrophages in the brain. Read More

    Impact of paroxetine on proximal β-adrenergic receptor signaling.
    Cell Signal 2017 Oct 12;38:127-133. Epub 2017 Jul 12.
    Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA. Electronic address:
    β-adrenergic receptors (βAR) regulate numerous functions throughout the body, however G protein-coupled receptor kinase (GRK)-dependent desensitization of βAR has long been recognized as a maladaptive process in the progression of various disease states. Thus, the development of small molecule inhibitors of GRKs for the study of these processes and as potential therapeutics has been at the forefront of recent research efforts. Via structural and biochemical analyses, the selective serotonin reuptake inhibitor (SSRI) paroxetine was identified as a GRK2 inhibitor that enhances βAR-dependent cardiomyocyte and cardiac contractility and reverses cardiac dysfunction and myocardial βAR expression in mouse models of heart failure. Read More

    Horizontal transfer of miR-106a/b from cisplatin resistant hepatocarcinoma cells can alter the sensitivity of cervical cancer cells to cisplatin.
    Cell Signal 2017 Oct 11;38:146-158. Epub 2017 Jul 11.
    Department of Biochemistry and Molecular Biology, Central University of Kerala, Nileshwar, Kasargod, Kerala, India. Electronic address:
    Recent studies indicate that horizontal transfer of genetic material can act as a communication tool between heterogenous populations of tumour cells, thus altering the chemosensitivity of tumour cells. The present study was designed to check whether the horizontal transfer of miRNAs released by cisplatin resistant (Cp-r) Hepatocarcinoma cells can alter the sensitivity of cervical cancer cells. For this exosomes secreted by cisplatin resistant and cisplatin sensitive HepG2 cells (EXres and EXsen) were isolated and characterised. Read More

    Hypoxia-induced suppression of c-Myc by HIF-2α in human pulmonary endothelial cells attenuates TFAM expression.
    Cell Signal 2017 Oct 12;38:230-237. Epub 2017 Jul 12.
    Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address:
    The adaptive response to hypoxia is mediated in large part by stabilization of the hypoxia-inducible factors, HIF-1α and HIF-2α. A hallmark of this response is the metabolic shift to decreased oxidative phosphorylation and increased glycolysis. We hypothesized that hypoxic responses would include a suppression of mitochondrial gene expression. Read More

    The protective role of TET2 in erythroid iron homeostasis against oxidative stress and erythropoiesis.
    Cell Signal 2017 Oct 8;38:106-115. Epub 2017 Jul 8.
    Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China. Electronic address:
    Although previous studies suggested that stress erythropoiesis and iron metabolism regulate each other to increase iron availability for hemoglobin synthesis, the molecular bases determining its different traits remain elusive. In addition, global DNA demethylation has been reported during mouse erythropoiesis in vivo. However, the understanding of iron-related genes through DNA demethylation under stress erythropoiesis is largely unknown. Read More

    The pivotal role of extracellular signal-regulated kinase in gap junction-mediated regulation of TXNIP.
    Cell Signal 2017 Oct 8;38:116-126. Epub 2017 Jul 8.
    Division of Molecular Signaling, Department of the Advanced Biomedical Research, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan. Electronic address:
    Gap junctions (GJs) play a major role in the control of cell structure, function, and metabolism. However, the molecular mechanisms involved are still poorly understood. Given that thioredoxin-interacting protein (TXNIP) regulates a broad range of cellular processes, we tested the possible involvement of TXNIP. Read More

    Sphingolipid abnormalities in cancer multidrug resistance: Chicken or egg?
    Cell Signal 2017 Oct 4;38:134-145. Epub 2017 Jul 4.
    Laboratory of Signal Transduction, Sloan Kettering Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, United States.
    The cancer multidrug resistance (MDR) phenotype encompasses a myriad of molecular, genetic and cellular alterations resulting from progressive oncogenic transformation and selection. Drug efflux transporters, in particular the MDR P-glycoprotein ABCB1, play an important role in MDR but cannot confer the complete phenotype alone indicating parallel alterations are prerequisite. Sphingolipids are essential constituents of lipid raft domains and directly participate in functionalization of transmembrane proteins, including providing an optimal lipid microenvironment for multidrug transporters, and are also perturbed in cancer. Read More

    Mitochondria elongation is mediated through SIRT1-mediated MFN1 stabilization.
    Cell Signal 2017 Oct 29;38:67-75. Epub 2017 Jun 29.
    Department of Biochemistry, Ajou University, School of Medicine and Graduate School, Suwon, 443-380, Republic of Korea; Department of Biomedical Sciences, Ajou University School of Medicine and Graduate School, Suwon, 443-380, Republic of Korea. Electronic address:
    Mitochondria are highly dynamic organelles that change size and morphology by fusing together or dividing through fission. In response to cellular cues, signaling cascades may post-translationally modify mitochondria-shaping proteins, which lead to a change in mitochondria morphology. Here we show that nicotinamide (NAM), an inhibitor of sirtuin deacetylases, promotes degradation of mitochondria fusion protein mitofusin 1 (MFN1), suggesting that acetylation status of MFN1 is important for its protein stability. Read More

    The tyrosine Y250(2.39) in Frizzled 4 defines a conserved motif important for structural integrity of the receptor and recruitment of Disheveled.
    Cell Signal 2017 Oct 29;38:85-96. Epub 2017 Jun 29.
    Laboratory of WNT Signaling, Institute of Experimental Biology, Faculty of Science, Masaryk University, Kotlarska 2, 61137 Brno, Czech Republic; Laboratory of Receptor Biology and Signaling, Department of Physiology and Pharmacology, Karolinska Institutet, Nanna Svartz väg 2, 17177, Stockholm, Sweden. Electronic address:
    Frizzleds (FZDs) are unconventional G protein-coupled receptors, which activate diverse intracellular signaling pathways via the phosphoprotein Disheveled (DVL) and heterotrimeric G proteins. The interaction interplay of FZDs with DVL and G proteins is complex, involves different regions of FZD and the potential dynamics are poorly understood. In the present study, we aimed to characterize the function of a highly conserved tyrosine (Y250(2. Read More

    PDE2 at the crossway between cAMP and cGMP signalling in the heart.
    Cell Signal 2017 Oct 28;38:76-84. Epub 2017 Jun 28.
    Department of Pharmacology and Toxicology, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Fetscherstraße 74, Dresden 01307, Germany. Electronic address:
    The cyclic nucleotides cAMP and cGMP are central second messengers in cardiac cells and critical regulators of cardiac physiology as well as pathophysiology. Consequently, subcellular compartmentalization allows for spatiotemporal control of cAMP/cGMP metabolism and subsequent regulation of their respective effector kinases PKA or PKG is most important for cardiac function in health and disease. While acute cAMP-mediated signalling is a mandatory prerequisite for the physiological fight-or-flight response, sustained activation of this pathway may lead to the progression of heart failure. Read More

    Smurf1 targets Securin for ubiquitin-dependent degradation and regulates the metaphase-to-anaphase transition.
    Cell Signal 2017 Oct 27;38:60-66. Epub 2017 Jun 27.
    Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Comparative Medical Center, Peking Union Medical College, Beijing, China. Electronic address:
    The HECT E3 ligase Smurf1 (Smad ubiquitination regulatory factor 1) plays a critical role in several important biological pathways by targeting many proteins for ubiquitination and degradation, such as Smad1/5, MEKK2 and RhoA. However, the function of Smurf1 in metaphase-to-anaphase transition remains unclear. Here, we show that Smurf1 interacts with and targets Securin, an inhibitor of sister-chromatid separation, for poly-ubiquitination and proteasomal degradation. Read More

    Downregulation of PKCζ/Pard3/Pard6b is responsible for lung adenocarcinoma cell EMT and invasion.
    Cell Signal 2017 Oct 24;38:49-59. Epub 2017 Jun 24.
    Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, USA; Cancer Center, University of Illinois at Chicago, Chicago, IL, USA; State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China. Electronic address:
    Atypical protein kinase C ζ (PKCζ) forms an apico-basal polarity complex with Partitioning Defective (Pard) 3 and Pard6 to regulate normal epithelial cell apico-basolateral polarization. The dissociation of the PKCζ/Pard3/Pard6 complex is essential for the disassembly of the tight/adherens junction and epithelial-mesenchymal transition (EMT) that is critical for tumor spreading. Loss of cell polarity and epithelial organization is strongly correlated with malignancy and tumor progression in some other cancer types. Read More

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