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Cellular Signalling

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https://www.readbyqxmd.com/read/29133163/non-visual-arrestins-regulate-the-focal-adhesion-formation-via-small-gtpases-rhoa-and-rac1-independently-of-gpcrs
#1
Whitney M Cleghorn, Nada Bulus, Seunghyi Kook, Vsevolod V Gurevich, Roy Zent, Eugenia V Gurevich
Arrestins recruit a variety of signaling proteins to active phosphorylated G protein-coupled receptors in the plasma membrane and to the cytoskeleton. Loss of arrestins leads to decreased cell migration, altered cell shape, and an increase in focal adhesions. Small GTPases of the Rho family are molecular switches that regulate actin cytoskeleton and affect a variety of dynamic cellular functions including cell migration and cell morphology. Here we show that non-visual arrestins differentially regulate RhoA and Rac1 activity to promote cell spreading via actin reorganization, and focal adhesion formation via two distinct mechanisms...
November 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29080804/blockade-of-cd38-diminishes-lipopolysaccharide-induced-macrophage-classical-activation-and-acute-kidney-injury-involving-nf-%C3%AE%C2%BAb-signaling-suppression
#2
Bingyan Shu, Ye Feng, Yuan Gui, Qingmiao Lu, Wei Wei, Xian Xue, Xiaoli Sun, Weichun He, Junwei Yang, Chunsun Dai
The CD38, possessing ADP-ribosyl cyclase (ADPR-cyclase) and cyclic ADP-ribose hydrolase (cADPR-hydrolase), is able to regulate a variety of cellular activities. However, the role and mechanisms for CD38 in macrophage activation and sepsis-induced acute kidney injury (AKI) remain to be determined. Here we report that in cultured macrophages, Lipopolysaccharide (LPS) could upregulate CD38 expression in time and dose dependent manner. Knocking down or blockade of CD38 in macrophages could inhibit LPS-induced macrophage M1 polarization accompanied by diminished NF-κB signaling activation...
November 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29128403/cln5-is-secreted-and-functions-as-a-glycoside-hydrolase-in-dictyostelium
#3
Robert J Huber, Sabateeshan Mathavarajah
Ceroid lipofuscinosis neuronal 5 (CLN5) is a member of a family of proteins that are linked to neuronal ceroid lipofuscinosis (NCL). This devastating neurological disorder, known commonly as Batten disease, affects all ages and ethnicities and is currently incurable. The precise function of CLN5, like many of the NCL proteins, remains to be elucidated. In this study, we report the localization, molecular function, and interactome of Cln5, the CLN5 homolog in the social amoeba Dictyostelium discoideum. Residues that are glycosylated in human CLN5 are conserved in the Dictyostelium homolog as are residues that are mutated in patients with CLN5 disease...
November 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29126977/enhancement-of-inosine-mediated-a2ar-signaling-through-positive-allosteric-modulation
#4
Ajith A Welihinda, Manmeet Kaur, Kaviya S Raveendran, Edward P Amento
Inosine is an endogenous nucleoside that is produced by metabolic deamination of adenosine. Inosine is metabolically more stable (half-life 15h) than adenosine (half-life <10s). Inosine exerts anti-inflammatory and immunomodulatory effects similar to those observed with adenosine. These effects are mediated in part through the adenosine A2A receptor (A2AR). Relative to adenosine inosine exhibits a lower affinity towards the A2AR. Therefore, it is generally believed that inosine is incapable of activating the A2AR through direct engagement, but indirectly activates the A2AR upon metabolic conversion to higher affinity adenosine...
November 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29126976/involvement-of-glucose-related-energy-crisis-and-endoplasmic-reticulum-stress-insinuation-of-streptozotocin-induced-alzheimer-s-like-pathology
#5
Joyshree Biswas, Sonam Gupta, Dinesh Kumar Verma, Parul Gupta, Abhishek Singh, Shubhangini Tiwari, Poonam Goswami, Sharad Sharma, Sarika Singh
The present study was conducted to correlate the cellular and molecular alterations in Alzheimer's pathology employing streptozotocin (STZ) induced experimental rat model. The STZ was administered in rat brain bilaterally by intracerebroventricular route using stereotaxic surgery followed by donepezil dosing. The Alzheimer's related pathological marker like acetylcholinesterase (AChE) activity, tau phosphorylation and amyloid aggregation were observed after STZ administration. STZ treatment showed decreased glucose and glucose transporters (GLUT) level along with augmented level of calcium in both cortical and hippocampal regions of rat brain...
November 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29102770/overexpression-of-djmj-differentially-affects-intestinal-stem-cells-and-differentiated-enterocytes
#6
Dang Ngoc Anh Suong, Kouhei Shimaji, Jung-Hoon Pyo, Joung-Sun Park, Hideki Yoshida, Mi-Ae Yoo, Masamitsu Yamaguchi
Jumonji (Jmj)/Jarid2 is a DNA-binding transcriptional repressor mediated via histone methylation. Nevertheless, the well-known function of Jmj is as a scaffold for the recruitment of various complexes including Polycomb repressive complex 2 (PRC2), and required for mouse embryonic stem cell development. However, PRC2 independent function is suggested for Drosophila Jumonji (dJmj). To clarify the function of dJmj during cell differentiation, we used Drosophila adult intestinal stem cell system that allows to follow stem cell behaviors in vivo...
November 2, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29102771/il-13-enhances-mesenchymal-transition-of-pulmonary-artery-endothelial-cells-via-down-regulation-of-mir-424-503-in-vitro
#7
Koichi Takagi, Munekazu Yamakuchi, Takahiro Matsuyama, Kiyotaka Kondo, Akifumi Uchida, Shunsuke Misono, Teruto Hashiguchi, Hiromasa Inoue
Pulmonary arterial hypertension (PAH) has a major effect on life expectancy with functional degeneracy of the lungs and right heart. Interleukin-13 (IL-13), one of the type 2 cytokines mainly associated with allergic diseases, has recently been reported to be associated with Schistosomiasis-associated PAH which shares pathological features with other forms of PAH, such as idiopathic PAH and connective tissue disease-associated PAH. But a direct pathological role of IL-13 in the development of PAH has not been explored...
November 1, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29101002/cellular-signaling-special-issue-to-celebrate-75th-birthday-of-prof-robert-j-lefkowitz
#8
EDITORIAL
Arun K Shukla, Nigel J Pyne
No abstract text is available yet for this article.
October 31, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29097258/site-specific-o-glycosylation-of-n-terminal-serine-residues-by-polypeptide-galnac-transferase-2-modulates-human-%C3%AE-opioid-receptor-turnover-at-the-plasma-membrane
#9
Jarkko J Lackman, Christoffer K Goth, Adnan Halim, Sergey Y Vakhrushev, Henrik Clausen, Ulla E Petäjä-Repo
G protein-coupled receptors (GPCRs) are an important protein family of signalling receptors that govern a wide variety of physiological functions. The capacity to transmit extracellular signals and the extent of cellular response are largely determined by the amount of functional receptors at the cell surface that is subject to complex and fine-tuned regulation. Here, we demonstrate that the cell surface expression level of an inhibitory GPCR, the human δ-opioid receptor (hδOR) involved in pain and mood regulation, is modulated by site-specific N-acetylgalactosamine (GalNAc) -type O-glycosylation...
October 31, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29074139/optogenetic-control-of-focal-adhesion-kinase-signaling
#10
Maximilian Hörner, Claire Chatelle, Wignand W D Mühlhäuser, David R Stocker, Michael Coats, Wilfried Weber, Gerald Radziwill
Focal adhesion kinase (FAK) integrates signaling from integrins, growth factor receptors and mechanical stress to control cell adhesion, motility, survival and proliferation. Here, we developed a single-component, photo-activatable FAK, termed optoFAK, by using blue light-induced oligomerization of cryptochrome 2 (CRY2) to activate FAK-CRY2 fusion proteins. OptoFAK functions uncoupled from physiological stimuli and activates downstream signaling rapidly and reversibly upon blue light exposure. OptoFAK stimulates SRC creating a positive feedback loop on FAK activation, facilitating phosphorylation of paxillin and p130Cas in adherent cells...
October 23, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29069608/uev1a-ubc13-catalyzes-k63-linked-ubiquitination-of-rhbdf2-to-promote-tace-maturation
#11
Yiran Zhang, Yadan Li, Xiaoran Yang, Juanjuan Wang, Ruifeng Wang, Xianghao Qian, Weiwei Zhang, Wei Xiao
The TNFα-induced NF-κB signaling pathway plays critical roles in multiple biological processes. Extensive studies have explored the mechanisms regulating this signaling cascade, and identified an E2 complex, Uev1A-Ubc13, that mediates K63-linked poly-Ub chain formation and thus recruits NEMO to activate the signaling transduction. In this study, we demonstrate that the Uev1A-Ubc13 complex simultaneously serves as a repressor of the NF-κB pathway. It was found that cells overexpressing UEV1A silence the signal cascade earlier than control cells...
October 22, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29056500/emerging-role-of-non-coding-rna-in-oral-cancer
#12
REVIEW
Fatemeh Momen-Heravi, Shashi Bala
Oral squamous cell carcinoma (OSCC) is characterized by genomic and epigenomic alterations. However, the mechanisms underlying oral squamous cell carcinoma tumorigenesis and progression remain to be elucidated. Long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and extracellular RNAs (exRNAs) are emerging groups of regulatory RNAs, which possess low or no protein-coding potential. Emerging lines of evidence indicates that deregulated expression of lncRNAs and circular RNAs are associated with the induction and progression of various cancers, including oral cancer, through epigenetic, transcriptional, and post-transcriptional alterations...
October 19, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29056499/the-allosteric-site-regulates-the-voltage-sensitivity-of-muscarinic-receptors
#13
Anika Hoppe, Maria Marti-Solano, Matthäus Drabek, Moritz Bünemann, Peter Kolb, Andreas Rinne
Muscarinic receptors (M-Rs) for acetylcholine (ACh) belong to the class A of G protein-coupled receptors. M-Rs are activated by orthosteric agonists that bind to a specific site buried in the M-R transmembrane helix bundle. In the active conformation, receptor function can be modulated either by allosteric modulators, which bind to the extracellular receptor surface or by the membrane potential via an unknown mechanism. Here, we compared the modulation of M1-Rs and M3-Rs induced by changes in voltage to their allosteric modulation by chemical compounds...
October 19, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29050986/rac1-plays-a-role-in-cxcl12-but-not-ccl3-induced-chemotaxis-and-rac1-gef-inhibitor-nsc23766-has-off-target-effects-on-cxcr4
#14
Shirley C Mills, Lesley Howell, Andrew Beekman, Leanne Stokes, Anja Mueller
Cell migration towards a chemotactic stimulus relies on the re-arrangement of the cytoskeleton, which is triggered by activation of small G proteins RhoA, Rac1 and Cdc42, and leads to formation of lamellopodia and actin polymerisation amongst other effects. Here we show that Rac1 is important for CXCR4 induced chemotaxis but not for CCR1/CCR5 induced chemotaxis. For CXCL12-induced migration via CXCR4, breast cancer MCF-7 cells are reliant on Rac1, similarly to THP-1 monocytes and Jurkat T-cells. For CCL3-induced migration via CCR1 and/or CCR5, Rac1 signalling does not regulate cell migration in either suspension or adherent cells...
October 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29050985/bromodomain-protein-brd4-promotes-cell-proliferation-in-skin-squamous-cell-carcinoma
#15
Tie Xiang, Jin-Yu Bai, Chang She, Dao-Jiang Yu, Xiao-Zhong Zhou, Tian-Lan Zhao
The present study examined the expression and biological functions of bromodomain-containing protein 4 (BRD4) in skin squamous cell carcinoma (SCC) cells. Our results show that BRD4 mRNA and protein expression was upregulated in human skin SCC cells, as compared to its level in the normal skin keratinocytes and fibroblasts. Treatment with BRD4 inhibitors, JQ1 and CPI203, resulted in proliferation inhibition, apoptosis and cell cycle arrest in both established (A431 cell line) and primary skin SCC cells. Furthermore, BRD4 knockdown (by targeted shRNAs) or knockout (by CRISPR/Cas9) largely inhibited A431 cell proliferation...
October 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29042286/protein-kinase-and-lipase-inhibitors-of-inositide-metabolism-deplete-ip7-indirectly-in-pancreatic-%C3%AE-cells-off-target-effects-on-cellular-bioenergetics-and-direct-effects-on-ip6k-activity
#16
Subu Surendran Rajasekaran, Christopher Illies, Stephen B Shears, Huanchen Wang, Thais S Ayala, Joilson O Martins, Elisabetta Daré, Per-Olof Berggren, Christopher J Barker
Inositol pyrophosphates have emerged as important regulators of many critical cellular processes from vesicle trafficking and cytoskeletal rearrangement to telomere length regulation and apoptosis. We have previously demonstrated that 5-di-phosphoinositol pentakisphosphate, IP7, is at a high level in pancreatic β-cells and is important for insulin exocytosis. To better understand IP7 regulation in β-cells, we used an insulin secreting cell line, HIT-T15, to screen a number of different pharmacological inhibitors of inositide metabolism for their impact on cellular IP7...
October 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29042285/regulating-the-regulators-epigenetic-transcriptional-and-post-translational-regulation-of-rgs-proteins
#17
REVIEW
Mohammed Alqinyah, Shelley B Hooks
Regulators of G protein signaling (RGS) are a family of proteins classically known to accelerate the intrinsic GTPase activity of G proteins, which results in accelerated inactivation of heterotrimeric G proteins and inhibition of G protein coupled receptor signaling. RGS proteins play major roles in essential cellular processes, and dysregulation of RGS protein expression is implicated in multiple diseases, including cancer, cardiovascular and neurodegenerative diseases. The expression of RGS proteins is highly dynamic and is regulated by epigenetic, transcriptional and post-translational mechanisms...
October 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29030113/proteomic-analyses-of-signalling-complexes-associated-with-receptor-tyrosine-kinase-identify-novel-members-of-fibroblast-growth-factor-receptor-3-interactome
#18
Lukas Balek, Pavel Nemec, Peter Konik, Michaela Kunova Bosakova, Miroslav Varecha, Iva Gudernova, Jirina Medalova, Deborah Krakow, Pavel Krejci
Receptor tyrosine kinases (RTKs) form multiprotein complexes that initiate and propagate intracellular signals and determine the RTK-specific signalling patterns. Unravelling the full complexity of protein interactions within the RTK-associated complexes is essential for understanding of RTK functions, yet it remains an understudied area of cell biology. We describe a comprehensive approach to characterize RTK interactome. A single tag immunoprecipitation and phosphotyrosine protein isolation followed by mass-spectrometry was used to identify proteins interacting with fibroblast growth factor receptor 3 (FGFR3)...
October 13, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29030114/impairment-of-energy-sensors-sirt1-and-ampk-in-lipid-induced-inflamed-adipocyte-is-regulated-by-fetuin-a
#19
Mrittika Chattopadhyay, Sandip Mukherjee, Subhendu K Chatterjee, Dipanjan Chattopadhyay, Snehasis Das, Subeer S Majumdar, Satinath Mukhopadhyay, Sutapa Mukherjee, Samir Bhattarcharya
Although several reports demonstrated that accumulation of excess lipid in adipose tissue produces defects in adipocyte which leads to the disruption of energy homeostasis causing severe metabolic problems, underlying mechanism of this event remains yet unclear. Here we demonstrate that FetuinA (FetA) plays a critical role in the impairment of two metabolic sensors, SIRT1 and AMPK, in inflamed adipocytes of high fat diet (HFD) mice. A linear increase in adipocyte hypertrophy from 10 to 16 week was in tandem with the increase in FetA and that coincided with SIRT1 cleavage and decrease in pAMPK which adversely affects PGC1α activation...
October 10, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29020611/tubulin-dependent-secretion-of-s100a6-and-cellular-signaling-pathways-activated-by-s100a6-integrin-%C3%AE-1-interaction
#20
Ewelina Jurewicz, Elżbieta Wyroba, Anna Filipek
S100A6 is a calcium binding protein expressed mainly in fibroblasts and epithelial cells. Interestingly, S100A6 is also present in extracellular fluids. Recently we have shown that S100A6 is secreted by WJMS cells and binds to integrin β1 (Jurewicz et al., 2014). In this work we describe for the first time the mechanism of S100A6 secretion and signaling pathways activated by the S100A6-integrin β1 complex. We show that colchicine suppressed the release of S100A6 into the cell medium, which indicates that the protein might be secreted via a tubulin-dependent pathway...
October 8, 2017: Cellular Signalling
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