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Cellular Signalling

T A Blair, S F Moore, T G Walsh, J L Hutchinson, T N Durrant, K E Anderson, A W Poole, I Hers
Phosphoinositide 3-kinase (PI3K) plays an important role in platelet function and contributes to platelet hyperreactivity induced by elevated levels of circulating peptide hormones, including thrombopoietin (TPO). Previous work established an important role for the PI3K isoform; p110β in platelet function, however the role of p110α is still largely unexplored. Here we sought to investigate the role of p110α in TPO-mediated hyperactivity by using a conditional p110α knockout (KO) murine model in conjunction with platelet functional assays...
May 21, 2018: Cellular Signalling
Steven Daniel Funk, Alexandra C Finney, Arif Yurdagul, Christopher B Pattillo, A Wayne Orr
Endothelial cell activation by proinflammatory stimuli drives leukocyte recruitment through enhanced expression of counter-receptors such as vascular cell adhesion molecule-1 (VCAM-1). We previously demonstrated that activation of the receptor tyrosine kinase EphA2 with its ligand ephrin-A1 induces VCAM-1 expression. Here, we sought to characterize the proinflammatory signaling pathways involved. Analysis of over-represented transcription factors in ephrin-A1-induced genes identified multiple potential transcriptional regulators, including the Rel family members nuclear factor-κB (NF-κB/p65) and nuclear factor of activated T-cells (NFAT)...
May 21, 2018: Cellular Signalling
Debdeep Dutta, Ankita Singh, Maimuna Sali Paul, Vartika Sharma, Mousumi Mutsuddi, Ashim Mukherjee
TNF-JNK signaling is one of the highly conserved signaling pathways that regulate a broad spectrum of cellular processes including proliferation and apoptosis. Eiger, the sole homologue of TNF in Drosophila, initiates the TNF-JNK pathway to induce cell death. Previously, Deltex (Dx) has been identified as a Notch signaling component that regulates vesicular trafficking of Notch. In the present study, we have investigated the interaction between these two proteins in order to identify how Dx influences the activity of Eiger...
May 15, 2018: Cellular Signalling
Gopinathan Pillai Sreekanth, Pa-Thai Yenchitsomanus, Thawornchai Limjindaporn
Dengue virus (DENV) infection is a disease that is endemic to many parts of the world, and its increasing prevalence ranks it among the diseases considered to be a significant threat to public health. The clinical manifestations of DENV infection range from mild dengue fever (DF) to more severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Increased proinflammatory cytokines and vascular permeability, both of which cause organ injury, are the hallmarks of severe dengue disease. Signs of liver injury were observed in studies using hepatic cell lines, mouse models, and autopsy specimens from DENV-infected patients, and these signs substantiated the effects of inflammatory responses and hepatic cell apoptosis...
May 10, 2018: Cellular Signalling
Jingwen Liu, Yuhan Chen, Qingyang Huang, Wen Liu, Xiqing Ji, Fan Hu, Ying Zhu, Lingqiang Zhang, Guanglong Dong
The endoplasmic reticulum (ER) is a cellular organelle with central roles in maintaining proteostasis. The accumulation of misfolded proteins in the ER lumen causes ER stress. Cells evoke an evolutionarily conserved adaptive signaling network "unfolded protein response" to restore ER homeostasis, however, how the signaling network is delicately orchestrated remains largely unrevealed. Meanwhile, the HECT type E3 ligase Smad ubiquitylation regulatory factor 1 (Smurf1) has been reported to play critical roles in several important biological pathways by targeting distinct substrates for ubiquitylation, including WFS1, a critical mediator of ER stress, whereas the regulation of Smurf1 activity and abundance upon ER stress are poorly understood...
May 9, 2018: Cellular Signalling
Toshiaki Tanaka, Mitsuyoshi Iino, Kaoru Goto
The signaling axis of p38 mitogen-activated protein kinase (p38 MAPK) and MAPK-activated protein kinase 2 (MK2) is the dominant pathway that leads to heat shock protein 27 (HSP27) phosphorylation. After activation of MK2 by p38 MAPK, HSP27 is phosphorylated and depolymerized by MK2, thereby increasing the cell migration and directly interfering with the apoptotic signaling cascades. Sec6 is one of the components of the exocyst complex that is an evolutionarily conserved 8-protein complex. Even though several studies have demonstrated that Sec6 is involved in various cellular physiological functions, the relationship between Sec6 and HSP27 or p38 MAPK during cell migration and apoptosis remains unclear...
May 2, 2018: Cellular Signalling
Marta Zarà, Ilaria Canobbio, Caterina Visconte, Jessica Canino, Mauro Torti, Gianni Francesco Guidetti
Tumor cell-induced platelet aggregation represents a critical process both for successful metastatic spread of the tumor and for the development of thrombotic complications in cancer patients. To get further insights into this process, we investigated and compared the molecular mechanisms of platelet aggregation induced by two different breast cancer cell lines (MDA-MB-231 and MCF7) and a colorectal cancer cell line (Caco-2). All the three types of cancer cells were able to induce comparable platelet aggregation, which, however, was observed exclusively in the presence of CaCl2 and autologous plasma...
April 26, 2018: Cellular Signalling
Melina Livitsanou, Eleftheria Vasilaki, Christos Stournaras, Dimitris Kardassis
We have shown previously that the small GTPases RhoA and RhoB play important roles in early TGFβ-induced actin cytoskeleton reorganization and that RhoB is transcriptionally activated by TGFβ and its signaling effectors, the Smad proteins. However, this long-term impact of RhoB gene upregulation by TGFβ on cellular functions is not known. We now show that increased levels of RhoB, but not of RhoA, inhibit the TGFβ/Smad-mediated transcriptional induction of the cell cycle inhibitor p21WAF1/Cip1 gene as well as of a generic Smad-responsive promoter suggesting that RhoB could be part of an auto-inhibitory loop in TGFβ signaling by inhibiting the genomic responses to TGFβ...
April 26, 2018: Cellular Signalling
Ke Hui, Shiqi Wu, Yangyang Yue, Yanan Gu, Bing Guan, Xinyang Wang, Jer-Tsong Hsieh, Luke S Chang, Dalin He, Kaijie Wu
Muscle-invasive or metastatic bladder cancer (BCa) is a life-threatening disease for patients, and tumor angiogenesis is believed to play a critical role in the progression of BCa. However, its underlying mechanism of tumor angiogenesis is still poorly understood. In this study, we discovered that RASAL2, a RAS GTPase activating protein, could inhibit BCa angiogenesis based on our shRNA/siRNA knockdown or ectopic cDNA expression experiments. Mechanistically, RASAL2 downregulation could enhance the phosphorylation of AKT and then subsequently upregulate the expression of ETS1 and VEGFA...
April 24, 2018: Cellular Signalling
A F M T Islam, Haicen Yue, Margarethakay Scavello, Pearce Haldeman, Wouter-Jan Rappel, Pascale G Charest
To study the dynamics and mechanisms controlling activation of the heterotrimeric G protein Gα2βγ in Dictyostelium in response to stimulation by the chemoattractant cyclic AMP (cAMP), we monitored the G protein subunit interaction in live cells using bioluminescence resonance energy transfer (BRET). We found that cAMP induces the cAR1-mediated dissociation of the G protein subunits to a similar extent in both undifferentiated and differentiated cells, suggesting that only a small number of cAR1 (as expressed in undifferentiated cells) is necessary to induce the full activation of Gα2βγ...
April 23, 2018: Cellular Signalling
Milton Roy, Dhanendra Tomar, Kritarth Singh, Sripada Lakshmi, Paresh Prajapati, Khyati Bhatelia, Dhruv Gohel, Rajesh Singh
In cancer patients, treatment modalities like chemotherapy and radiation exert their anticancer effects by inducing DNA damage. The cancer cells can survive under genotoxic stress by inducing DNA damage response (DDR) or can undergo cell death. The process of autophagy is emerging as crucial regulator of cell survival during different stress conditions. Post translational modification through ubiquitin plays an essential role in DDR during genotoxic stress conditions. Ubiquitin ligases regulate autophagy and cell death pathways however their role during genotoxic stress conditions is not understood...
April 17, 2018: Cellular Signalling
Emma Harper, Keith D Rochfort, Hannah Forde, Colin Davenport, Diarmuid Smith, Philip M Cummins
BACKGROUND: The intimal endothelium is known to condition the underlying medial smooth muscle cell (SMC) layer of the vessel wall, and is highly responsive to receptor-activator of nuclear factor-κB ligand (RANKL) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), pro-calcific and anti-calcific agents, respectively. In this paper, we tested the hypothesis that RANKL-induced activation of endothelial NF-κB signalling is essential for pro-calcific activation of the underlying SMCs...
April 17, 2018: Cellular Signalling
Quangdon Tran, Jae-Hun Jung, Jisoo Park, Hyunji Lee, Youngeun Hong, Hyeonjeong Cho, Minhee Kim, Sungjin Park, So-Hee Kwon, Seon-Hwan Kim, George Thomas, Kwang Pyo Kim, Myung-Haing Cho, Jongsun Park
Mitochondrial morphology, which is associated with changes in metabolism, cell cycle, cell development and cell death, is tightly regulated by the balance between fusion and fission. In this study, we found that S6 kinase 1 (S6K1) contributes to mitochondrial dynamics, homeostasis and function. Mouse embryo fibroblasts lacking S6K1 (S6K1-KO MEFs) exhibited more fragmented mitochondria and a higher level of Dynamin related protein 1 (Drp1) and active Drp1 (pS616) in both whole cell extracts and mitochondrial fraction...
April 16, 2018: Cellular Signalling
Song Hee Kim, Won Hyeok Lee, Seong Who Kim, Je Hyoung Uk, Jong Cheol Lee, Hyo Won Chang, Young Min Kim, Kyungbin Kim, Sang Yoon Kim, Myung Woul Han
Radiotherapy is a well-established therapeutic modality used in the treatment of many cancers. However, radioresistance remains a serious obstacle to successful treatment. Radioresistance can cause local recurrence and distant metastases in some patients after radiation treatment. Thus, many studies have attempted to identify effective radiosensitizers. Eph receptor functions contribute to tumor development, modulating cell-cell adhesion, invasion, neo-angiogenesis, tumor growth and metastasis. However, the role of EphA3 in radioresistance remains unclear...
April 10, 2018: Cellular Signalling
Maha M Hammad, Henry A Dunn, Stephen S G Ferguson
MAGI proteins are Membrane-Associated Guanylate Kinase Inverted proteins that belong to the MAGUK family. They are scaffolding proteins that were shown to mediate the trafficking and signaling of various G protein-coupled receptors (GPCRs). They contain PDZ domains in their structure and most GPCRs interact with these proteins via the PDZ motifs on the carboxyl terminal end of a receptor. In a PDZ overlay assay performed with the carboxyl terminal tail of 5-HT2A R, we were able to detect all three members of the MAGI subfamily, MAGI-1, MAGI-2 and MAGI-3 as interacting PDZ proteins...
April 3, 2018: Cellular Signalling
Maria Schönrogge, Hagen Kerndl, Xianbin Zhang, Simone Kumstel, Brigitte Vollmar, Dietmar Zechner
Multiple studies are currently targeting dysregulated cancer cell metabolism with distinct combinations of inhibitors. In this study, we evaluated in pancreatic cancer cells metformin, which blocks oxidative phosphorylation, in combination with α-cyano-4-hydroxycinnamate, which has been reported to inhibit the export of lactate from the cytosol. The combination of metformin with α-cyano-4-hydroxycinnamate had a major inhibitory effect on the migration of 6606PDA cells. Monotherapy with α-cyano-4-hydroxycinnamate and especially the combination with metformin also caused significant inhibition of cell proliferation and induced cell death...
March 30, 2018: Cellular Signalling
Shanxin Li, Zhipeng Han, Naping Zhao, Bing Zhu, Qianwen Zhang, Xue Yang, Dandan Sheng, Jing Hou, Shiwei Guo, Lixin Wei, Li Zhang
Cancer stem cell (CSC) theory reveals a new insight into the understanding of tumorigenesis and metastasis. Recently, DNA methylation is suggested to be a potential epigenetic mechanism for maintenance of CSCs. What's more, studies have shown that DNA methyltransferase (DNMT) is essential for CSCs and deletion of DNMT can reduce tumorigenesis by limiting CSC pool. Therefore, targeting the epigenetic modifiers especially DNA methylation offers an optional strategy for treating human cancers. In the present study we found that DNMT inhibitor 5-Aza-2'-deoxycytidine (5-AzaDC) markedly reduced colorectal CSC abundance in vitro and suppressed liver metastatic tumor growth in vivo...
March 27, 2018: Cellular Signalling
Wen Zeng, Jiansong Tang, Haicheng Li, Haixia Xu, Hongyun Lu, Hangya Peng, Chuwen Lin, Rili Gao, Shuo Lin, Keyi Lin, Kunying Liu, Yan Jiang, Jianping Weng, Longyi Zeng
Lipotoxicity leads to insulin secretion deficiency, which is among the important causes for the onset of type 2 diabetes mellitus. Thus, the restoration of β-cell mass and preservation of its endocrine function are long-sought goals in diabetes research. Previous studies have suggested that the membrane protein caveolin-1 (Cav-1) is implicated in β-cell apoptosis and insulin secretion, however, the underlying mechanisms still remains unclear. Our objective is to explore whether Cav-1 depletion protects pancreatic β cells from lipotoxicity and what are the underlying mechanisms...
March 26, 2018: Cellular Signalling
Justin F Deniset, Thomas E Hedley, Markéta Hlaváčková, Mirna N Chahine, Elena Dibrov, Kim O'Hara, Graham G Maddaford, David Nelson, Thane G Maddaford, Robert Fandrich, Elissavet Kardami, Grant N Pierce
AIM: Heat shock protein 60 (Hsp60) is a mediator of stress-induced vascular smooth muscle cell (VSMC) proliferation. This study will determine, first, if the mitochondrial or cytoplasmic localization of Hsp60 is critical to VSMC proliferation and, second, the mechanism of Hsp60 induction of VSMC proliferation with a focus on modification of nucleocytoplasmic trafficking. METHODS AND RESULTS: Hsp60 was overexpressed in primary rabbit VSMCs with or without a mitochondrial targeting sequence (AdHsp60mito- )...
March 26, 2018: Cellular Signalling
Magdalena Zaremba-Czogalla, Anita Hryniewicz-Jankowska, Renata Tabola, Miroslaw Nienartowicz, Kamilla Stach, Jaroslaw Wierzbicki, Roberto Cirocchi, Piotr Ziolkowski, Sabina Tabaczar, Katarzyna Augoff
Metastasis is the leading cause of mortality in patients with highly invasive cancers and, as such, is a major problem for medicine. It has been increasingly recognized that cancer-related inflammation plays an important role in promoting invasion and the metastatic process in which cell motility and upregulation of proteolytic enzymes are crucial events. TNFα is a proinflammatory cytokine known to stimulate synthesis of MMP9, a zinc- and calcium-dependent endopeptidase contributing to the regulation of ECM remodeling and cell signaling...
March 24, 2018: Cellular Signalling
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