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Cellular Signalling

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https://www.readbyqxmd.com/read/28927666/the-role-of-a-kinase-anchoring-proteins-in-cancer-development
#1
REVIEW
Erica Reggi, Dario Diviani
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...
September 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28927665/fgd5-sustains-vascular-endothelial-growth-factor-a-vegfa-signaling-through-inhibition-of-proteasome-mediated-vegf-receptor-2-degradation
#2
Johan Heldin, Paul O'Callaghan, Rodrigo Hernández Vera, Peder Fredlund Fuchs, Pär Gerwins, Johan Kreuger
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. The latter finding prompted us to explore if FGD5 regulates VEGFR2 dynamics...
September 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28927664/the-c1-domain-of-vav3-a-novel-potential-therapeutic-target
#3
Jessica S Kelsey, Tamás Géczy, Christopher J Kaler, Peter M Blumberg
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...
September 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28923416/cocaine-modulates-allosteric-d2-%C3%AF-1-receptor-receptor-interactions-on-dopamine-and-glutamate-nerve-terminals-from-rat-striatum
#4
Sarah Beggiato, Andrea Celeste Borelli, Dasiel Borroto-Escuela, Ilaria Corbucci, Maria Cristina Tomasini, Matteo Marti, Tiziana Antonelli, Sergio Tanganelli, Kjell Fuxe, Luca Ferraro
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...
September 15, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28923415/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
#5
Hossam Draz, Alexander A Goldberg, Vladimir I Titorenko, Emma Guns, Stephen H Safe, J Thomas Sanderson
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. We found that DIM and ring-DIMs induced autophagy was accompanied by increased autophagic vacuole formation and conversion of LC3BI to LC3BII in LNCaP and C42B human prostate cancer cells...
September 15, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28911860/glucose-elicits-serine-threonine-kinase-vrk1-to-phosphorylate-nuclear-pregnane-x-receptor-as-a-novel-hepatic-gluconeogenic-signal
#6
Saki Gotoh, Yuu Miyauchi, Rick Moore, Masahiko Negishi
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. In low glucose conditions, VRK1 directly phosphorylates PXR at Ser(350), enabling PO3-PXR to scaffold protein phosphatase PP2Cα...
September 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28911859/recent-development-of-signaling-pathways-inhibitors-of-melanogenesis
#7
REVIEW
Thanigaimalai Pillaiyar, Manoj Manickam, Sang-Hun Jung
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...
September 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28888686/fibroblast-derived-hgf-drives-acinar-lung-cancer-cell-polarization-through-integrin-dependent-rhoa-rock1-inhibition
#8
Anirban Datta, Emma Sandilands, Keith E Mostov, David M Bryant
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...
September 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28887229/mapk-activation-patterns-of-at1r-and-cb1r-in-shr-versus-wistar-astrocytes-evidence-of-cb1r-hypofunction-and-crosstalk-between-at1r-and-cb1r
#9
Dhanush Haspula, Michelle A Clark
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...
September 5, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28867659/t-darpp-stimulates-protein-kinase-a-activity-by-forming-a-complex-with-its-ri-regulatory-subunit
#10
Dirk Theile, Shuhui Geng, Erin C Denny, Jamil Momand, Susan E Kane
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...
September 1, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28867658/identification-and-characterization-of-a-potent-and-biologically-active-pde4-7-inhibitor-via-fission-yeast-based-assays
#11
Ana Santos de Medeiros, Arlene R Wyman, Manal A Alaamery, Christina Allain, F Douglas Ivey, Lili Wang, Hai Le, James P Morken, Alawi Habara, Cuong Le, Shuaiying Cui, Adam Lerner, Charles S Hoffman
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...
September 1, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28866365/store-operated-calcium-entry-is-dispensable-for-the-activation-of-erk1-2-pathway-in-prostate-cancer-cells
#12
Aida M Lopez-Guerrero, Carlos Pascual-Caro, Francisco Javier Martin-Romero, Eulalia Pozo-Guisado
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...
August 31, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28851628/pde8-controls-cd4-t-cell-motility-through-the-pde8a-raf-1-kinase-signaling-complex
#13
Chaitali P Basole, Rebecca K Nguyen, Katie Lamothe, Amanda Vang, Robert Clark, George S Baillie, Paul M Epstein, Stefan Brocke
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. To examine T cell motility under physiologic conditions, we analyzed T cell interactions with endothelial cells and ligands in flow assays...
August 26, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28844868/complexity-of-the-wnt-%C3%AE-%C3%A2-catenin-pathway-searching-for-an-activation-model
#14
REVIEW
Giovane G Tortelote, Renata R Reis, Fabio de Almeida Mendes, Jose Garcia Abreu
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. They participate in a plethora of functions during the development of an organism, from axial specification, gastrulation and organogenesis all the way to regeneration and repair in adults...
August 26, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28844867/integrated-stress-response-stimulates-fgf21-expression-systemic-enhancer-of-longevity
#15
REVIEW
Antero Salminen, Kai Kaarniranta, Anu Kauppinen
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. The stress kinases of the integrated stress response (ISR) pathway stimulate the expression of FGF21 through the activation of ATF4 transcription factor, thus enhancing cellular stress resistance. The metabolic and stress-inducible transactivation mechanisms of FGF21 gene are mostly mediated through separate pathways...
August 24, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28843696/ngf-protects-endothelial-cells-from-indomethacin-induced-injury-through-activation-of-mitochondria-and-upregulation-of-igf-1
#16
Amrita Ahluwalia, Michael K Jones, Neil Hoa, Andrzej S Tarnawski
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., ethanol and nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, indomethacin, diclofenac], especially in gastric mucosa that has direct exposure to these agents. In this study, we investigated whether nerve growth factor (NGF) can protect gastric microvascular ECs (GECs) from injury by indomethacin (INDO) and the mechanisms involved...
August 24, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28826907/protein-kinase-c-isoforms-in-the-normal-pancreas-and-in-pancreatic-disease
#17
REVIEW
Alicia K Fleming, Peter Storz
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. We also discuss the contribution of PKC enzymes to pancreatic diseases, including insulin resistance and diabetes mellitus, as well as pancreatitis and the development and progression of pancreatic cancer...
August 18, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28751007/corrigendum-to-palmitoylation-of-the-tp%C3%AE-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
#18
https://www.readbyqxmd.com/read/28743549/pyruvate-kinase-m1-interacts-with-a-raf-and-inhibits-endoplasmic-reticulum-stress-induced-apoptosis-by-activating-mek1-erk-pathway-in-mouse-insulinoma-cells
#19
Yuta Horiuchi, Daiki Nakatsu, Fumi Kano, Masayuki Murata
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...
July 22, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28734787/selenium-deficiency-induced-thioredoxin-suppression-and-thioredoxin-knock-down-disbalanced-insulin-responsiveness-in-chicken-cardiomyocytes-through-pi3k-akt-pathway-inhibition
#20
Jie Yang, Sattar Hamid, Jingzeng Cai, Qi Liu, Shiwen Xu, Ziwei Zhang
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. However, the roles of Txn and Txn system in insulin modulated cardiac energy metabolism have been less reported...
July 19, 2017: Cellular Signalling
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