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Cellular Signalling

Emma L Low, Andrew H Baker, Angela C Bradshaw
Excessive vascular smooth muscle cell (SMC) proliferation, migration and extracellular matrix (ECM) synthesis are key events in the development of intimal hyperplasia, a pathophysiological response to acute or chronic sources of vascular damage that can lead to occlusive narrowing of the vessel lumen. Atherosclerosis, the primary cause of coronary artery disease, is characterised by chronic vascular inflammation and dyslipidemia, while revascularisation surgeries such as coronary stenting and bypass grafting represent acute forms of vascular injury...
September 15, 2018: Cellular Signalling
Zhan Wang, Xingcheng Chen, Mei-Zuo Zhong, Shuping Yang, Jiuli Zhou, David L Klinkebiel, Adam R Karpf, Yuanhong Chen, Jixin Dong
YES is a member of the SRC family kinase (SFK) group of non-receptor tyrosine kinases, which are implicated in multiple key cellular processes involved in oncogenesis. Antitubulin agents have been widely used as chemotherapeutics for cancer patients and these drugs arrest cells in mitosis, leading to subsequent cell death. In the present study, we define a mechanism for phospho-regulation of YES that is critical for its role in response to antitubulin agents. Specifically, we found that YES is phosphorylated at multiple sites on its N-terminal unique domain by the cell cycle kinase CDK1 during antitubulin drug-induced mitotic arrest...
September 15, 2018: Cellular Signalling
Xin Tong, Qifan Zhang, Lu Wang, Yizhong Ji, Lei Zhang, Liwei Xie, Wei Chen, Huabing Zhang
RING finger 186 (RNF186) is involved in the process of endoplasmic reticulum (ER)-stress-mediated apoptosis and inflammation of different cell types, such as HeLa cells and colon epithelial cells. However, the physiological and functional roles of RNF186 in peripheral tissues remain largely unknown. In the current study, we investigate the physiological function of RNF186 in the regulation of ER stress with respect to its biological roles in regulating insulin sensitivity in mouse primary hepatocytes. RNF186 expression is induced in the livers of diabetic, obese and diet-induced obese (DIO) mice...
September 14, 2018: Cellular Signalling
Jixuan Liu, Wei Yan, Xiaojing Zhao, Qian Jia, Jinda Wang, Huawei Zhang, Chunlei Liu, Kunlun He, Zhijun Sun
Mitochondrial damage is involved in the pathogenesis of post-infarction cardiac injury. However, the upstream regulators of mitochondrial damage have not yet been identified. The aim of our study is to explore the role of Sirt3 in post-infarction cardiac injury with a particular focus on mitochondrial fission and AMPK-Drp1 pathways. Our results indicated that Sirt3 was downregulated in the progression of post-infarction cardiac injury. Overexpression of Sirt3 attenuated cardiac fibrosis, sustained myocardial function, inhibited the inflammatory response, and reduced cardiomyocyte death...
September 13, 2018: Cellular Signalling
Nataliia V Shults, Faisal S Almansour, Vladyslava Rybka, Dante I Suzuki, Yuichiro J Suzuki
Extracellular signal-regulated kinase (ERK), also known as classical mitogen-activated protein kinase, plays critical roles in cell regulation. ERK is activated through phosphorylation by a cascade of protein kinases including MEK. Various ligands activate the MEK/ERK pathway through receptor-dependent cell signaling. In cultured cells, many ligands such as growth factors, hormones, cytokines and vasoactive peptides elicit transient activation of MEK/ERK, often peaking at ~10 min after the cell treatment...
September 10, 2018: Cellular Signalling
Sheikh F Ahmad, Mushtaq A Ansari, Ahmed Nadeem, Saleh A Bakheet, Musaad A Alshammari, Mohammad R Khan, Abdulaziz M S Alsaad, Sabry M Attia
Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose symptoms include communication deficits, a lack of social skills, and stereotyped repetitive behaviors. We used BTBR T+ Itpr3tf /J (BTBR) mice, a model that demonstrates most of the core behavioral features of ASD, such as decreased sociability and high levels of repetitive behaviors. Currently, there is no treatment available that is able to improve most of the ASD disorder symptoms; thus, finding novel therapies is immediately required...
September 10, 2018: Cellular Signalling
Alexandra Vander Ark, Jingchen Cao, Xiaohong Li
Transforming growth factor β (TGF-β) plays an important role in normal development and homeostasis. Dysregulation of TGF-β responsiveness and its downstream signaling pathways contribute to many diseases, including cancer initiation, progression, and metastasis. TGF-β ligands bind to three isoforms of the TGF-β receptor (TGFBR) with different affinities. TGFBR1 and 2 are both serine/threonine and tyrosine kinases, but TGFBR3 does not have any kinase activity. They are necessary for activating canonical or noncanonical signaling pathways, as well as for regulating the activation of other signaling pathways...
September 7, 2018: Cellular Signalling
Bohee Jang, Hyejung Jung, Heejeong Hong, Eok-Soo Oh
Cell surface receptors must specifically recognize an extracellular ligand and then trigger an appropriate response within the cell. Their general structure enables this, as it comprises an extracellular domain that can bind an extracellular ligand, a cytoplasmic domain that can transduce a signal inside the cell to produce an appropriate response, and a transmembrane domain that links the two and is responsible for accurately delivering specific information on a binding event from the extracellular domain to the cytoplasmic domain, to trigger the proper response...
September 6, 2018: Cellular Signalling
Moon-Sung Lee, Hee-Jung Byun, Jaeseob Lee, Doo-Il Jeoung, Young-Myeong Kim, Hansoo Lee
Tetraspanin membrane proteins form physical complexes with signaling molecules and have been suggested to influence the signaling events of associated molecules. Of the tetraspanin proteins, CD82 has been shown to promote homotypic cell-cell adhesion, which partially accounts for its role in suppressing cancer invasion and metastasis. We found here that CD82-induced cell-cell adhesion is attributed to increased E-cadherin expression through CD82-mediated downregulation of the E-cadherin repressor Snail. The Snail repression by CD82 resulted from the reduced binding of the Sp1 transcription factor to the Snail gene promoter...
September 4, 2018: Cellular Signalling
Ela Markovsky, Elisa de Stanchina, Aryeh Itzkowitz, Adriana Haimovitz-Friedman, Susan A Rotenberg
Engineered overexpression of protein kinase Cα (PKCα) is known to phosphorylate Ser165 in α-tubulin resulting in stimulated microtubule dynamics and cell motility, and activation of an epithelial-mesenchymal transition (EMT) in non-transformed human breast cells. Here it is shown that endogenous phosphorylation of native α-tubulin in two metastatic breast cell lines, MDA-MB-231-LM2-4175 and MDA-MB-468 is detected at PKC phosphorylation sites. α-Tubulin mutants that simulated phosphorylated (S165D) or non-phosphorylated (S165 N) states were stably expressed in MDA-MB-231-LM2-4175 cells...
September 1, 2018: Cellular Signalling
Chengye Che, Cui Li, Jing Lin, Jie Zhang, Nan Jiang, Kelan Yuan, Guiqiu Zhao
Fungal keratitis causes devastating corneal ulcers which can result in significant visual impairment and even blindness. As a ligand that activates the non-canonical Wnt signaling pathways, Wnt5a triggers the production of important inflammatory chemokines and the chemotactic migration of neutrophils. In this study we aimed to characterize the role of Wnt5a production, in situ, in vivo and in vitro in response to fungal keratitis. Wnt5a expression in corneas of Aspergillus fumigatus (A. fumigatus) keratitis patients was determined by quantitative polymerase chain reaction (qRT-PCR) and immunofluorescence...
August 31, 2018: Cellular Signalling
Robert P Feehan, Amanda M Nelson, Lisa M Shantz
The primary cause of non-melanoma skin cancer (NMSC) is ultraviolet B (UVB) radiation. We have shown previously that mTORC2 inhibition sensitizes keratinocytes to UVB-induced apoptosis mediated by the transcription factor FOXO3a. FOXO3a is a key regulator of apoptosis and a tumor suppressor in several cancer types. Activation of FOXO3a promotes apoptosis through the coordinated expression of a variety of target genes, including TRAIL and NOXA. We hypothesized that in the setting of mTORC2 inhibition, the UVB-induced expression of these factors would lead to apoptosis in a FOXO3a-dependent manner...
August 30, 2018: Cellular Signalling
Agne Frismantiene, Maria Philippova, Paul Erne, Therese J Resink
Vascular smooth muscle cells (VSMCs) are the major cell type in blood vessels. Unlike many other mature cell types in the adult body, VSMC do not terminally differentiate but retain a remarkable plasticity. Fully differentiated medial VSMCs of mature vessels maintain quiescence and express a range of genes and proteins important for contraction/dilation, which allows them to control systemic and local pressure through the regulation of vascular tone. In response to vascular injury or alterations in local environmental cues, differentiated/contractile VSMCs are capable of switching to a dedifferentiated phenotype characterized by increased proliferation, migration and extracellular matrix synthesis in concert with decreased expression of contractile markers...
August 30, 2018: Cellular Signalling
Caterina Visconte, Jessica Canino, Gianni Francesco Guidetti, Marta Zarà, Claudio Seppi, Aisha Alsheikh Abubaker, Giordano Pula, Mauro Torti, Ilaria Canobbio
Amyloid precursor protein (APP) is the precursor of amyloid β (Aβ) peptides, whose accumulation in the brain is associated with Alzheimer's disease. APP is also expressed on the platelet surface and Aβ peptides are platelet agonists. The physiological role of APP is largely unknown. In neurons, APP acts as an adhesive receptor, facilitating integrin-mediated cell adhesion, while in platelets it regulates coagulation and venous thrombosis. In this work, we analyzed platelets from APP KO mice to investigate whether membrane APP supports platelet adhesion to physiological and pathological substrates...
August 30, 2018: Cellular Signalling
Li Zeng, Shichen Sun, Dong Han, Yang Liu, Haochen Liu, Hailan Feng, Yixiang Wang
Long noncoding RNAs (lncRNAs) are emerging as important regulators in molecular processes and may play vital roles in odontogenic differentiation of human dental pulp stem cells (hDPSCs). However, their functions remain to be elucidated. As lncRNA H19 is one of the most classical lncRNA, which plays essential roles in cellular differentiation, thus we explored the effects and mechanisms of H19 in odontogenic differentiation of hDPSCs. Stable overexpression and knockdown of H19 in hDPSCs were constructed using recombinant lentiviruses containing H19 and short hairpin-H19 expression cassettes, respectively...
August 27, 2018: Cellular Signalling
Nadine Rommerswinkel, Silvia Keil, Alshaimaa Adawy, Jan G Hengstler, Bernd Niggemann, Kurt S Zänker, Thomas Dittmar
The interplay of ErbB receptor homo- and heterodimers plays a crucial role in the pathology of breast cancer since activated signal transduction cascades coordinate proliferation, survival and migration of cells. EGF and β-Heregulin are well characterised ligands known to induce ErbB homo- and heterodimerisation, which have been associated with disease progression. In the present study, we investigated the impact of both factors on the migration of MDA-NEO and MDA-HER2 human breast cancer cells. MDA-NEO cells are positive for EGFR and HER3, while MDA-HER2 cells express EGFR, HER2 and HER3...
August 27, 2018: Cellular Signalling
Zheng-Wen Nie, Ying-Jie Niu, Wenjun Zhou, Yong-Han Kim, Kyung-Tae Shin, Xiang-Shun Cui
Thiamethoxam (TMX) is a neonicotinoid insecticide. It has specific high toxicity to insects. Residues of TMX have been detected in various crops. Early embryo quality is vital for fertility. Excessive production of reactive oxygen species (ROS) can override embryonic antioxidant defenses, producing oxidative stress that triggers apoptosis, necrosis, and/or permanent DNA damage responses in the early embryo. Comparative studies have indicated that TMX hepatotoxicity is significant in mammals in acute tests, but little is known about accumulated chronic toxicity in early embryonic development...
August 23, 2018: Cellular Signalling
Wolfgang Eberhardt, Usman Nasrullah, Josef Pfeilschifter
The calcineurin inhibitors (CNI) cyclosporine A (CsA) and tacrolimus represent potent immunosuppressive agents frequently used for solid organ transplantation and treatment of autoimmune disorders. Despite of their immense therapeutic benefits, residual fibrosis mainly in the kidney represents a common side effect of long-term therapy with CNI. Regardless of the immunosuppressive action, an increasing body of evidence implicates that a drug-induced increase in TGFβ and subsequent activation of TGFβ-initiated signaling pathways is closely associated with the development and progression of CNI-induced nephropathy...
August 23, 2018: Cellular Signalling
Helena J Janse van Rensburg, Dulcie Lai, Taha Azad, Yawei Hao, Xiaolong Yang
WW domain-containing transcriptional regulator 1 (TAZ) is a transcriptional co-activator and effector of the Hippo signaling pathway. In certain breast cancer subtypes, Hippo signaling is dysregulated leading to activation of TAZ and altered expression of TAZ transcriptional targets. Over the past decade, we and others have found that TAZ transcriptionally regulates genes that affect multiple aspects of breast cancer cell behaviour. However, while cancer cell-intrinsic oncogenic functions of TAZ have emerged, less is known about whether TAZ might also contribute to tumourigenesis by sensitizing tumour cells to factors present in the tumour microenvironment or in systemic circulation...
August 20, 2018: Cellular Signalling
B Wahlang, C McClain, S Barve, L Gobejishvili
No abstract text is available yet for this article.
July 2, 2018: Cellular Signalling
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