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Cellular Signalling

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https://www.readbyqxmd.com/read/28214588/the-experiences-of-a-biochemist-in-the-evolving-world-of-g-protein-dependent-signaling
#1
REVIEW
Richard A Cerione
This review describes how a biochemist and basic researcher (i.e. myself) came to make a career in the area of receptor-coupled signal transduction and the roles cellular signaling activities play both in normal physiology and in disease. Much of what has been the best part of this research life is due to the time I spent with Bob Lefkowitz (1982-1985), during an extraordinary period in the emerging field of G-protein-coupled receptors. Among my laboratory colleagues were some truly outstanding scientists including Marc Caron, the late Jeffrey Stadel, Berta Strulovici, Jeff Benovic, Brian Kobilka, and Henrik Dohlman, as well as many more...
February 15, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28214587/paqr3-augments-amino-acid-deprivation-induced-autophagy-by-inhibiting-mtorc1-signaling
#2
Lin Wang, Yi Pan, Meiqin Huang, Xue You, Feifan Guo, Yan Chen
Amino acids are the key activators of the mTOR complex 1 (mTORC1, mainly composed of mTOR, Raptor and mLST8) required for cell growth and proliferation. On the other hand, deprivation of amino acids induces autophagy via inhibition of mTORC1 signaling. We report here that amino acid-induced mTORC1 activity and amino acid deprivation-induced autophagy are regulated by PAQR3, a tumor suppressor. At the cellular level, PAQR3 negatively regulates amino acid-induced activation of mTORC1. The N-terminal end of PAQR3 interacts with the WD domains of Raptor and mLST8 directly...
February 15, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28229933/nuclear-lamins-and-progerin-are-dispensable-for-antioxidant-nrf2-response-to-arsenic-and-cadmium
#3
Kazunori Hashimoto, Rima Majumdar, Yoshiaki Tsuji
Lamins are important constituents of the nuclear inner membrane and provide a platform for transcription factors and chromatin. Progerin, a C-terminal truncated lamin A mutant, causes premature aging termed Hutchinson-Gilford Progeria Syndrome (HGPS). Oxidative stress appears to be involved in the pathogenesis of HGPS, although the mechanistic role of progerin remains elusive. Here we examined whether nuclear lamins are important for a cellular antioxidant mechanism, and whether progerin compromises it. We investigated the activation of nuclear factor-E2-related factor 2 (Nrf2) which regulates various antioxidant genes including heme oxygenase-1 (HMOX1), following exposure to sodium arsenite or cadmium chloride in lamin knockdown human cell lines and primary HGPS human fibroblasts...
February 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28212865/casein-kinase-2-interacting-protein-1-regulates-m1-and-m2-inflammatory-macrophage-polarization
#4
Yuhan Chen, Wen Liu, Yiwu Wang, Luo Zhang, Jun Wei, Xueli Zhang, Fuchu He, Lingqiang Zhang
The importance of macrophage plasticity, albeit being discovered recently, has been highlighted in a broad spectrum of biological processes operative in physiological and pathological environments. Macrophage polarized activation and inactivation has profound effects on immune and inflammatory responses with several major pathways being elucidated in the past few years. However, transcriptional regulation mechanisms governing macrophage polarization is still preliminary. In this study, we identify the Casein Kinase 2 Interacting Protein 1 (CKIP-1) as a molecular toggle manipulating macrophage speciation...
February 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28212864/gpr43-activation-enhances-psoriasis-like-inflammation-through-epidermal-upregulation-of-il-6-and-dual-oxidase-2-signaling-in-a-murine-model
#5
Ahmed Nadeem, Sheikh F Ahmad, Naif O Al-Harbi, Ahmed M El-Sherbeeny, Mohammed M Al-Harbi, Talal S Almukhlafi
The gut is densely inhabited by commensal bacteria, which metabolize dietary fibers/undigested carbohydrates and produce short-chain fatty acids such as acetate. GPR43 is one of the receptors to sense short-chain fatty acids, and expressed in various immune and non-immune cells. Acetate/GPR43 signaling has been shown to affect various inflammatory diseases through Th17 responses and NADPH oxidase (NOX)-derived reactive oxygen species (ROS) generation. However, no study has previously explored the effects of GPR43 activation during psoriasis-like inflammation...
February 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28229932/csn5-jab1-suppresses-the-wnt-inhibitor-dkk1-in-colorectal-cancer-cells
#6
Sandra Jumpertz, Thomas Hennes, Yaw Asare, Anke K Schütz, Jürgen Bernhagen
The COP9 signalosome (CSN) is a multi-protein complex that is highly conserved in eukaryotes. Due to its regulatory impact on processes such as cell cycle, DNA damage response and apoptosis, the CSN is essential for mammalian cells. One of the best-studied functions of the CSN is the deNEDDylation of cullin-RING ligases (CRLs) via its catalytically active subunit CSN5/JAB1, thereby triggering the degradation of various target proteins. CSN5 was found to be overexpressed in many human cancer entities, including colon adenocarcinoma...
February 13, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28216291/ovarian-tumor-domain-containing-protein-1-deubiquitinates-and-stabilizes-p53
#7
Shudong Piao, Han Zhong Pei, Bin Huang, Suk-Hwan Baek
Ubiquitination and deubiquitination pathways play important roles in the regulation of p53 stability and activity. p53 is ubiquitinated and destabilized by E3 ubiquitin ligases and is deubiquitinated and stabilized by deubiquitinases (DUBs). We screened ovarian tumor (OTU) subfamily proteins to identify novel DUBs that stabilized p53. OTU domain-containing protein 1 (OTUD1) is a DUB belonging to the OTU family; however, its substrates and its role in cells are unknown. Here, we used an overexpression and knockdown system to show that OTUD1 is a novel regulator of p53 stability...
February 13, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28193539/dimeric-but-not-monomeric-%C3%AE-lactalbumin-potentiates-apoptosis-by-up-regulation-of-atf3-and-reduction-of-histone-deacetylase-activity-in-primary-and-immortalised-cells
#8
Julie A Sharp, Amelia J Brennan, Galina Polekhina, David B Ascher, Christophe Lefevre, Kevin R Nicholas
α-lactalbumin is a protein of dual function found in milk of most mammals. α-lactalbumin binds β-1,4-galactosyltransferase to form the regulatory subunit for lactose synthesis and has also been shown to cause cell death. This study shows, for the first time, that α-lactalbumin isolated in a rare 28kDa dimeric form induces cell death, while 14kDa monomeric α-lactalbumin is inactive. In contrast to the casein derived and chemically induced α-lactalbumin variants, MAL and HAMLET/BAMLET, the effects of 28kDa α-lactalbumin are calcium independent and, unlike MAL and HAMLET, 28kDa α-lactalbumin dimer causes cell death of primary mammary cells and a variety of immortalised cell lines, which are committed to cell death pathways within 1-4h of exposure...
February 10, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28192161/enzymatic-cleavage-of-myoferlin-releases-a-dual-c2-domain-module-linked-to-erk-signalling
#9
Ann-Katrin Piper, Samuel E Ross, Gregory M Redpath, Frances A Lemckert, Natalie Woolger, Adam Bournazos, Peter A Greer, Roger B Sutton, Sandra T Cooper
Myoferlin and dysferlin are closely related members of the ferlin family of Ca(2+)-regulated vesicle fusion proteins. Dysferlin is proposed to play a role in Ca(2+)-triggered vesicle fusion during membrane repair. Myoferlin regulates endocytosis, recycling of growth factor receptors and adhesion proteins, and is linked to the metastatic potential of cancer cells. Our previous studies establish that dysferlin is cleaved by calpains during membrane injury, with the cleavage motif encoded by alternately-spliced exon 40a...
February 10, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28192162/transcriptional-regulation-of-rack1-and-modulation-of-its-expression-role-of-steroid-hormones-and-significance-in-health-and-aging
#10
Erica Buoso, Marilisa Galasso, Melania Maria Serafini, Melania Ronfani, Cristina Lanni, Emanuela Corsini, Marco Racchi
The Receptor for Activated C Kinase 1 (RACK1) is a scaffold protein for different kinases and membrane receptors. RACK1 can shuttle proteins to their sites of action, facilitate cross-talk among distinct signaling pathways or recruit other signaling proteins into the complexes. Therefore, it is a key mediator of various pathways and is involved in various biological events including development, immune response, brain activity and cancer. Because of its importance, it is of extreme significance to understand the transcriptional mechanisms governing its expression...
February 9, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28189587/reverting-p53-activation-after-recovery-of-cellular-stress-to-resume-with-cell-cycle-progression
#11
REVIEW
Pedro A Lazo
The activation of p53 in response to different types of cellular stress induces several protective reactions including cell cycle arrest, senescence or cell death. These protective effects are a consequence of the activation of p53 by specific phosphorylation performed by several kinases. The reversion of the cell cycle arrest, induced by p53, is a consequence of the phosphorylated and activated p53, which triggers its own downregulation and that of its positive regulators. The different down-regulatory processes have a sequential and temporal order of events...
February 9, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28189586/regulation-of-inflammation-by-%C3%AE-arrestins-not-just-receptor-tales
#12
REVIEW
Neil J Freedman, Sudha K Shenoy
The ubiquitously expressed, multifunctional scaffolding proteins β-arrestin1 and β-arrestin2 each affect inflammatory signaling in a variety of cell lines. In addition to binding the carboxyl-terminal tails of innumerable 7-transmembrane receptors, β-arrestins scaffold untold numbers of other plasma membrane and cytoplasmic proteins. Consequently, the effects of β-arrestins on inflammatory signaling are diverse, and context-specific. This review highlights the roles of β-arrestins in regulating canonical activation of the pro-inflammatory transcription factor NFκB...
February 9, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28189585/transcriptional-and-post-transcriptional-regulation-of-cdc20-during-the-spindle-assembly-checkpoint-in-s-cerevisiae
#13
Ruiwen Wang, Janet L Burton, Mark J Solomon
The anaphase-promoting complex (APC) is a ubiquitin ligase responsible for promoting the degradation of many cell cycle regulators. One of the activators and substrate-binding proteins for the APC is Cdc20. It has been shown previously that Cdc20 can promote its own degradation by the APC in normal cycling cells mainly through a cis-degradation mode (i.e. via an intramolecular mechanism). However, how Cdc20 is degraded during the spindle assembly checkpoint (SAC) is still not fully clear. In this study, we used a dual-Cdc20 system to investigate this issue and found that the cis-degradation mode is also the major pathway responsible for Cdc20 degradation during the SAC...
February 9, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28188824/the-g-protein-coupled-receptor-n-terminus-and-receptor-signalling-n-tering-a-new-era
#14
REVIEW
James L J Coleman, Tony Ngo, Nicola J Smith
G protein-coupled receptors (GPCRs) are a vast family of membrane-traversing proteins, essential to the ability of eukaryotic life to detect, and mount an intracellular response to, a diverse range of extracellular stimuli. GPCRs have evolved with archetypal features including an extracellular N-terminus and intracellular C-terminus that flank a transmembrane structure of seven sequential helices joined by intracellular and extracellular loops. These structural domains contribute to the ability of a GPCR to be correctly synthesised and inserted into the cell membrane, to interact with its cognate ligand(s) and to couple with signal-transducing heterotrimeric G proteins, allowing the activated receptor to selectively modulate a number of signalling cascades...
February 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28188823/hepatic-stellate-cell-interferes-with-nk-cell-regulation-of-fibrogenesis-via-curcumin-induced-senescence-of-hepatic-stellate-cell
#15
Huanhuan Jin, Yan Jia, Zhen Yao, Jingjing Huang, Meng Hao, Shunyu Yao, Naqi Lian, Feng Zhang, Chenxi Zhang, Xingran Chen, Mianli Bian, Jiangjuan Shao, Li Wu, Anping Chen, Shizhong Zheng
Hepatic fibrosis, a common scarring response to various forms of chronic liver injury, is a precursor to cirrhosis and liver cancer. During liver fibrosis, hepatic stellate cells (HSCs) initially activate and proliferate, which are responsible for the secretion of extracellular matrix components. However, these cells eventually senesce and are cleared by natural killer (NK) cells. Our previous researches have shown that the natural product curcumin could promote the senescence of activated HSC. In this study, we investigated how NK cells target senescent HSC and assessed the effect of this process on liver fibrosis...
February 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28179144/plasma-membrane-reorganization-links-acid-sphingomyelinase-ceramide-to-p38-mapk-pathways-in-endothelial-cells-apoptosis
#16
Colin Niaudet, Stéphanie Bonnaud, Maëva Guillonneau, Sébastien Gouard, Marie-Hélène Gaugler, Soizic Dutoit, Natacha Ripoche, Nolwenn Dubois, Valérie Trichet, Isabelle Corre, François Paris
The p38 MAPK signaling pathway is essential in the cellular response to stress stimuli, in particular in the endothelial cells that are major target of external stress. The importance of the bioactive sphingolipid ceramide generated by acid sphingomyelinase is also firmly established in stress-induced endothelial apoptotic cell death. Despite a suggested link between the p38 MAPK and ceramide pathways, the exact molecular events of this connection remain elusive. In the present study, by using two different activators of p38 MAPK, namely anisomycin and ionizing radiation, we depicted how ceramide generated by acid sphingomyelinase was involved in p38 MAPK-dependent apoptosis of endothelial cells...
February 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28167233/taste-and-smell-gpcrs-in-the-lung-evidence-for-a-previously-unrecognized-widespread-chemosensory-system
#17
REVIEW
Steven S An, Stephen B Liggett
Taste and smell receptor expression has been traditionally limited to the tongue and nose. We have identified bitter taste receptors (TAS2Rs) and olfactory receptors (ORs) on human airway smooth muscle (HASM) cells. TAS2Rs signal to PLCβ evoking an increase in [Ca(2+)]i causing membrane hyperpolarization and marked HASM relaxation ascertained by single cell, ex vivo, and in vivo methods. The presence of TAS2Rs in the lung was unexpected, as was the bronchodilatory function which has been shown to be due to signaling within specific microdomains of the cell...
February 4, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28161490/structural-analysis-of-ribosomal-rack1-and-its-role-in-translational-control
#18
Maja Holch Nielsen, Rasmus Kock Flygaard, Lasse Bohl Jenner
Receptor for Activated C-Kinase 1 (RACK1) belongs to the WD40 family of proteins, known to act as scaffolding proteins in interaction networks. Accordingly, RACK1 is found to have numerous interacting partners ranging from kinases and signaling proteins to membrane bound receptors and ion channels. Interestingly, RACK1 has also been identified as a ribosomal protein present in all eukaryotic ribosomes. Structures of eukaryotic ribosomes have shown RACK1 to be located at the back of the head of the small ribosomal subunit...
February 1, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28161489/antiproliferative-effects-of-bortezomib-in-endothelial-cells-transformed-by-viral-g-protein-coupled-receptor-associated-to-kaposi-s-sarcoma
#19
A Suares, M Mori Sequeiros Garcia, C Paz, V González-Pardo
The Kaposi's Sarcoma-associated Herpes virus G Protein-Coupled Receptor (vGPCR) is a key molecule in the pathogenesis of Kaposi Sarcoma. We have previously demonstrated that the proteasome inhibitor Bortezomib inhibits NF-κB pathway, which is required for tumor maintenance in endothelial cells that express vGPCR (vGPCR cells). In this work, we further investigated Bortezomib anti-proliferative mechanism of action. We demonstrated that Bortezomib decreases vGPCR cell number in a dose-dependent manner and induces cell morphology changes...
February 1, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28137506/gpcr-desensitization-acute-and-prolonged-phases
#20
REVIEW
Sudarshan Rajagopal, Sudha K Shenoy
G protein-coupled receptors (GPCRs) transduce a wide array of extracellular signals and regulate virtually every aspect of physiology. While GPCR signaling is essential, overstimulation can be deleterious, resulting in cellular toxicity or uncontrolled cellular growth. Accordingly, nature has developed a number of mechanisms for limiting GPCR signaling, which are broadly referred to as desensitization, and refer to a decrease in response to repeated or continuous stimulation. Short-term desensitization occurs over minutes, and is primarily associated with β-arrestins preventing G protein interaction with a GPCR...
January 28, 2017: Cellular Signalling
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