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Cellular Signalling

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https://www.readbyqxmd.com/read/28535874/coupling-between-the-trpc3-ion-channel-and-the-ncx1-transporter-contributed-to-vegf-induced-erk1-2-activation-and-angiogenesis-in-human-primary-endothelial-cells
#1
Andrikopoulos Petros, Suzanne A Eccles, Muhammad M Yaqoob
It has been previously demonstrated that the bi-directional transporter Na(+)/Ca(2+) exchanger (NCX) working in the reverse (Ca(2+)-influx) - mode promotes the activation of ERK1/2 in response to the key pro-angiogenic cytokine VEGF in human endothelial cells (ECs). However, the molecular event(s) that elicit NCX reversal in VEGF-stimulated ECs remain unclear. Here we investigated whether Na(+) influx via the diacylglycerol (DAG) - activated non-selective cation channel TRPC3 was functionally associated with NCX and whether its activity was required for VEGF-induced ERK1/2 activation and angiogenesis...
May 20, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28528970/the-many-faces-of-compartmentalized-pka-signalosomes
#2
REVIEW
Omar Torres-Quesada, Johanna E Mayrhofer, Eduard Stefan
Cellular signal transmission requires the dynamic formation of spatiotemporally controlled molecular interactions. At the cell surface information is received by receptor complexes and relayed through intracellular signaling platforms which organize the actions of functionally interacting signaling enzymes and substrates. The list of hormone or neurotransmitter pathways that utilize the ubiquitous cAMP-sensing protein kinase A (PKA) system is expansive. This requires that the specificity, duration, and intensity of PKA responses are spatially and temporally restricted...
May 18, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28506929/inhibition-of-cell-proliferation-and-induction-of-autophagy-by-kdm2b-fbxl10-knockdown-in-gastric-cancer-cells
#3
Erhu Zhao, Chunling Tang, Xiaolan Jiang, Xiong Weng, Xiaoxia Zhong, Dunke Zhang, Jianbing Hou, Feng Wang, Mengying Huang, Hongjuan Cui
Gastric cancer is difficult to cure due to its clinical heterogeneity and the complexity of its molecular mechanisms. KDM2B, a member of the JHDM family, functions as a histone lysine demethylase. However, the role and mechanisms of KDM2B in gastric cancer have not been elucidated. Here, we showed that KDM2B is commonly expressed in gastric cancer cells. The downregulation of KDM2B immediately induces autophagy, followed by the inhibition of proliferation. The compound 3-methyladenine (3-MA), an inhibitor of autophagy, largely rescues autophagy and the inhibition of cell proliferation induced by KDM2B knockdown...
May 12, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28506928/distinct-phosphodiesterase-5a-containing-compartments-allow-selective-regulation-of-cgmp-dependent-signalling-in-human-arterial-smooth-muscle-cells
#4
Lindsay S Wilson, Manhong Guo, M Bibiana Umana, Donald H Maurice
Cyclic GMP (cGMP) translates and integrates much of the information encoded by nitric oxide (NO(·)) and several natriuretic peptides, including the atrial natriuretic peptide (ANP). Previously, we reported that integration of a cGMP-specific cyclic nucleotide phosphodiesterase, namely phosphodiesterase 5A (PDE5A), into a protein kinase G (PKG)- and inositol-1,4,5-trisphosphate receptor (IP3R)-containing endoplasmic reticulum (ER) signalosome allows localized control of PDE5A activity and of PKG-dependent inhibition of IP3-mediated release of ER Ca(2+) in human platelets...
May 12, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28502587/direct-and-indirect-activation-of-eukaryotic-elongation-factor-2-kinase-by-amp-activated-protein-kinase
#5
M Johanns, S Pyr Dit Ruys, A Houddane, D Vertommen, G Herinckx, L Hue, C G Proud, M H Rider
BACKGROUND: Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is a key regulator of protein synthesis in mammalian cells. It phosphorylates and inhibits eEF2, the translation factor necessary for peptide translocation during the elongation phase of protein synthesis. When cellular energy demand outweighs energy supply, AMP-activated protein kinase (AMPK) and eEF2K become activated, leading to eEF2 phosphorylation, which reduces the rate of protein synthesis, a process that consumes a large proportion of cellular energy under optimal conditions...
May 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28499884/inhibition-of-ubiquitin-specific-protease-34-usp34-induces-epithelial-mesenchymal-transition-and-promotes-stemness-in-mammary-epithelial-cells
#6
Eunhye Oh, Ji Young Kim, Daeil Sung, Youngkwan Cho, Nahyun Lee, Hyunsook An, Yoon-Jae Kim, Tae-Min Cho, Jae Hong Seo
Ubiquitin-specific protease 34 (USP34) is a deubiquitinating enzyme that regulates Axin stability and plays a critical role in Wnt/β-catenin signaling. We sought to investigate the role of USP34 on epithelial-mesenchymal (EMT) induction and its effects on mammary epithelial stem cells. USP34 expression levels were relatively lower in MDA-MB-231 and 4T1 mesenchymal-like cells when compared to epithelial-like cells. Inhibition of USP34 in NMuMG cells induced EMT, as evidenced by the upregulation of EMT markers including N-cadherin, phospho-Smad3, Snail and active-β-catenin, as well as the downregulation of Axin 1 and E-cadherin...
May 10, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28495591/the-hla-dr-mediated-signalling-increases-the-migration-and-invasion-of-melanoma-cells-the-expression-and-lipid-raft-recruitment-of-adhesion-receptors-pd-l1-and-signal-transduction-proteins
#7
Francesca Costantini, Giovanna Barbieri
The constitutive expression of Major Histocompatibility Complex (MHC) class II molecules is restricted to professional Antigen-Presenting Cells (APCs), nevertheless almost 50% of melanomas express constitutively the MHC class II molecules. Therefore, in two MHC class II constitutive expressing melanoma cell lines we studied the signalling mediated by the HLA-DR molecules in the aim to understand the consequence of class II mediated signalling on metastatic dissemination of melanoma. In particular, we reported that the HLA-DR mediated signalling play a new role in melanoma progression, increasing the migration and invasion of melanoma cells...
May 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28495590/concurrent-activation-of-%C3%AE-2-adrenergic-receptor-and-blockage-of-gpr55-disrupts-pro-oncogenic-signaling-in-glioma-cells
#8
Artur Wnorowski, Justyna Such, Rajib K Paul, Robert P Wersto, Fred E Indig, Krzysztof Jozwiak, Michel Bernier, Irving W Wainer
Activation of β2-adrenergic receptor (β2AR) and deorphanized GPR55 has been shown to modulate cancer growth in diverse tumor types in vitro and in xenograft models in vivo. (R,R')-4'-methoxy-1-naphthylfenoterol [(R,R')-MNF] is a bivalent compound that agonizes β2AR but inhibits GPR55-mediated pro-oncogenic responses. Here, we investigated the molecular mechanisms underlying the anti-tumorigenic effects of concurrent β2AR activation and GPR55 blockade in C6 glioma cells using (R,R')-MNF as a marker ligand...
May 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28495589/reduced-fak-stat3-signaling-contributes-to-er-stress-induced-mitochondrial-dysfunction-and-death-in-endothelial-cells
#9
Kalpita Banerjee, Matt P Keasey, Vladislav Razskazovskiy, Nishant P Visavadiya, Cuihong Jia, Theo Hagg
Excessive endoplasmic reticulum (ER) stress leads to cell loss in many diseases, e.g., contributing to endothelial cell loss after spinal cord injury. Here, we determined whether ER stress-induced mitochondrial dysfunction could be explained by interruption of the focal adhesion kinase (FAK)-mitochondrial STAT3 pathway we recently discovered. ER stress was induced in brain-derived mouse bEnd5 endothelial cells by thapsigargin or tunicamycin and caused apoptotic cell death over a 72h period. In concert, ER stress caused mitochondrial dysfunction as shown by reduced bioenergetic function, loss of mitochondrial membrane potential and increased mitophagy...
May 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28495495/translating-in-vitro-ligand-bias-into-in-vivo-efficacy
#10
REVIEW
Louis M Luttrell, Stuart Maudsley, Diane Gesty-Palmer
It is increasingly apparent that ligand structure influences both the efficiency with which G protein-coupled receptors (GPCRs) engage their downstream effectors and the manner in which they are activated. Thus, 'biased' agonists, synthetic ligands whose intrinsic efficacy differs from the native ligand, afford a strategy for manipulating GPCR signaling in ways that promote beneficial signals while blocking potentially deleterious ones. Still, there are significant challenges in relating in vitro ligand efficacy, which is typically measured in heterologous expression systems, to the biological response in vivo, where the ligand is acting on natively expressed receptors and in the presence of the endogenous ligand...
May 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28487119/the-mammalian-ste20-like-kinase-1-mst1-is-a-substrate-for-the-apoptosis-inhibiting-protein-kinase-ck2
#11
Christina Servas, Sandra Kiehlmeier, Julia Hach, Rebecca Gross, Claudia Götz, Mathias Montenarh
Apoptosis and the response to cell stress are evolutionary highly conserved mechanisms. Both processes require strict regulation, which is often performed by protein kinases. The mammalian Sterile 20-like kinase 1 (MST1) is a pro-apoptotic protein kinase, which is activated and cleaved by caspases upon the induction of cell stress. Being a phosphoprotein itself, the activity of MST1 is regulated by phosphorylation. Protein kinase CK2 is an anti-apoptotic protein kinase which seems to be involved in the regulation of many different cellular processes including apoptosis...
May 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28483635/crystal-structure-of-tissue-factor-in-complex-with-antibody-10h10-reveals-the-signaling-epitope
#12
Alexey Teplyakov, Galina Obmolova, Thomas J Malia, Bingyuan Wu, Yonghong Zhao, Susann Taudte, G Mark Anderson, Gary L Gilliland
Tissue factor (TF) initiates the extrinsic pathway of blood coagulation through sequential binding and activation of coagulation factors VII (FVII) and X (FX). In addition, through activation of G-protein-coupled protease activated receptors (PARs) TF induces cell signaling that is related to cancer, angiogenesis and inflammation. Monoclonal antibodies (mAbs) proved to be a useful tool for studying the interplay between TF signaling and coagulation. MAb 10H10 is unique in that it blocks the signaling pathway and thus inhibits angiogenesis and tumor growth without interfering with coagulation...
May 5, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28483634/protein-mediated-regulation-of-the-nhe1-isoform-of-the-na-h-exchanger-in-renal-cells-a-regulatory-role-of-hsp90-and-akt-kinase
#13
Ayodeji Odunewu-Aderibigbe, Larry Fliegel
Na(+)/H(+) exchanger isoform one (NHE1) is a pH regulatory protein that is present in renal tissues and serves to remove protons from within cells and protect against intracellular acidification. NHE1 has a large 315 amino acid cytosolic regulatory domain that regulates the catalytic membrane domain. We examined protein-mediated regulation of NHE1 through the cytosolic domain. Affinity chromatography with the C-terminus of NHE1 yielded a number of NHE1 binding proteins including 14-3-3 protein, heat shock proteins (Hsp90 and Hsp70) and Na(+)/K(+) ATPase...
May 5, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28479297/nkx3-2-induces-oxygen-concentration-independent-and-lysosome-dependent-degradation-of-hif-1%C3%AE-to-modulate-hypoxic-responses-in-chondrocytes
#14
Suhjean Im, Dae-Won Kim
Hypoxia-inducible factor 1-alpha (HIF-1α) is a DNA-binding transcription factor regulating hypoxic responses. It plays a key role in vascularization and angiogenesis as well as various metabolic pathways. Interestingly, during early phase endochondral ossification when HIF expression in chondrocytes is evident, developing cartilage primordia remains avascular until hypertrophic calcification commences. In this work, we uncovered a novel pathway causing oxygen concentration-independent and proteasome-independent degradation of HIF-1α protein...
May 4, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28473198/subcellular-distribution-of-rad23b-controls-xpc-degradation-and-dna-damage-repair-in-response-to-chemotherapy-drugs
#15
Xue You, Weiwei Guo, Lin Wang, Yongfan Hou, Huanhuan Zhang, Yi Pan, Ruomei Han, Meiqin Huang, Lujian Liao, Yan Chen
The RAD23B-XPC complex in the nucleus plays a key role in the initial damage recognition during global genome nucleotide excision repair (NER). Within the complex, XPC, a product of Xeroderma pigmentosum C, recognizes and interacts with the unpaired bases in the undamaged DNA strand, while RAD23B stabilizes XPC. However, how RAD23B is regulated by other factors is not well known. We report here a mode of spatial regulation of RAD23B that controls XPC stability and DNA damage repair. We first identified that RAD23B was able to directly associate with PAQR3, a newly-discovered tumor suppressor implicated in many types of human cancers...
May 1, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28465009/crk-adaptor-proteins-regulate-cd3%C3%AE-chain-phosphorylation-and-tcr-cd3-down-modulation-in-activated-t-cells
#16
Guangyu Dong, Rachel Kalifa, Pulak Ranjan Nath, Yael Babichev, Sigal Gelkop, Noah Isakov
T cell receptor (TCR) recognition of a peptide antigen in the context of MHC molecules initiates positive and negative cascades that regulate T cell activation, proliferation and differentiation, and culminate in the acquisition of effector T cell functions. These processes are a prerequisite for the induction of specific T cell-mediated adaptive immune responses. A key event in the activation of TCR-coupled signaling pathways is the phosphorylation of tyrosine residues within the cytoplasmic tails of the CD3 subunits, predominantly CD3ζ...
April 29, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28461104/differential-manipulation-of-arrestin-3-binding-to-basal-and-agonist-activated-g-protein-coupled-receptors
#17
Susanne Prokop, Nicole A Perry, Sergey A Vishnivetskiy, Andras D Toth, Asuka Inoue, Graeme Milligan, Tina M Iverson, Laszlo Hunyady, Vsevolod V Gurevich
Non-visual arrestins interact with hundreds of different G protein-coupled receptors (GPCRs). Here we show that by introducing mutations into elements that directly bind receptors, the specificity of arrestin-3 can be altered. Several mutations in the two parts of the central "crest" of the arrestin molecule, middle-loop and C-loop, enhanced or reduced arrestin-3 interactions with several GPCRs in receptor subtype and functional state-specific manner. For example, the Lys139Ile substitution in the middle-loop dramatically enhanced the binding to inactive M2 muscarinic receptor, so that agonist activation of the M2 did not further increase arrestin-3 binding...
April 28, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28455144/identification-of-nck1-as-a-novel-downstream-effector-of-stat3-in-colorectal-cancer-metastasis-and-angiogenesis
#18
Fan Zhang, Yan-Xia Lu, Qing Chen, Hui-Mei Zou, Jian-Ming Zhang, Yu-Han Hu, Xiao-Min Li, Wen-Juan Zhang, Wei Zhang, Chun Lin, Xue-Nong Li
Signal transducer and activator of transcription 3 (STAT3) is known to activate targets associated with invasion, proliferation, and angiogenesis in a wide variety of cancers. The adaptor protein NCK1 is involved in cytoskeletal movement and was identified as a STAT3-associated target in human tumors. However, the underlying molecular mechanism associated with colorectal cancer (CRC) metastasis is not yet completely understood. In this study, we report a novel STAT3 to NCK1 signaling pathway in colorectal cancer (CRC)...
April 25, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28455143/ire1%C3%AE-links-nck1-deficiency-to-attenuated-ptp1b-expression-in-hepg2-cells
#19
Hui Li, Bing Li, Louise Larose
PTP1B, a prototype of the non-receptor subfamily of the protein tyrosine phosphatase superfamily, plays a key role in regulating intracellular signaling from various receptor and non-receptor protein tyrosine kinases. Previously, we reported that silencing Nck1 in human hepatocellular carcinoma HepG2 cells enhances basal and growth factor-induced activation of the PI3K-Akt pathway through attenuating PTP1B expression. However, the underlying mechanism by which Nck1 depletion represses PTP1B expression remains unclear...
April 25, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28449948/sunitinib-specifically-augments-glucose-induced-insulin-secretion
#20
Stefan Z Lutz, Axel Ullrich, Hans-Ulrich Häring, Susanne Ullrich, Felicia Gerst
The tyrosine kinase inhibitor sunitinib is used for the treatment of numerous cancers in humans. In diabetic patients, sunitinib lowers blood glucose levels and improves glycaemic control. This study aims to analyse whether sunitinib has specific and direct effects on insulin secreting β-cells. Regulation of insulin secretion, of cellular cAMP levels and activation of signalling pathways were examined upon exposure of rat insulinoma INS-1E cells to sunitinib under specific stimulatory and inhibitory conditions...
April 24, 2017: Cellular Signalling
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