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Cellular Signalling

Ping Gao, Wen Wu, Jiemei Ye, Yao Wei Lu, Alejandro Pablo Adam, Harold A Singer, Xiaochun Long
Transforming growth factor β (TGFβ) signaling plays crucial roles in maintaining vascular integrity and homeostasis, and is established as a strong activator of vascular smooth muscle cell (VSMC) differentiation. Chronic inflammation is a hallmark of various vascular diseases. Although TGFβ signaling has been suggested to be protective against inflammatory aortic aneurysm progression, its exact effects on VSMC inflammatory process and the underlying mechanisms are not fully unraveled. Here we revealed that TGFβ1 suppressed the expression of a broad array of proinflammatory genes while potently induced the expression of contractile genes in cultured primary human coronary artery SMCs (HCASMCs)...
July 10, 2018: Cellular Signalling
Edit Szodorai, Konstantina Bampali, Roman A Romanov, Siegfried Kasper, Tomas Hökfelt, Margot Ernst, Gert Lubec, Tibor Harkany
In the hippocampus, GABA inhibition tunes network oscillations and shapes synchronous activity during spatial learning and memory coding. Once released from the presynapse, GABA primarily binds to ionotropic GABAA receptors (GABAA Rs), which are heteropentamers combinatorially assembled from nineteen known subunits to induce Cl- currents postsynaptically. Dissecting GABAA R subtype specificities in neurobiology is daunting because of differences in their developmental dynamics, regional distribution and subcellular compartmentalization...
July 10, 2018: Cellular Signalling
Lili Donner, Lothar Gremer, Tamar Ziehm, Christoph G W Gertzen, Holger Gohlke, Dieter Willbold, Margitta Elvers
A pathological hallmark of Alzheimer's disease (AD) is the aggregation of amyloid-β peptides (Aβ) into fibrils, leading to deposits in cerebral parenchyma and vessels known as cerebral amyloid angiopathy (CAA). Platelets are major players of hemostasis but are also implicated in AD. Recently we provided strong evidence for a direct contribution of platelets to AD pathology. We found that monomeric Aβ40 binds through its RHDS sequence to integrin αIIb β3 , and promotes the formation of fibrillar Aβ aggregates by the secretion of adenosine diphosphate (ADP) and the chaperone protein clusterin (CLU) from platelets...
June 29, 2018: Cellular Signalling
Jingliao Zhang, Zhifu Xiang, Priyangi A Malaviarachchi, Yan Yan, Nicholas J Baltz, Peter D Emanuel, Y Lucy Liu
Constitutively activated MAPK and AKT signaling pathways are often found in solid tumors and leukemias. PTEN is one of the tumor suppressors that are frequently found deficient in patients with late-stage cancers or leukemias. In this study we demonstrate that a MAPK inhibitor, PD98059, inhibits both AKT and ERK phosphorylation in a human myeloid leukemia cell line (TF-1), but not in PTEN-deficient leukemia cells (TF-1a). Ectopic expression of wild-type PTEN in myeloid leukemia cells restored cytokine responsiveness at physiological concentrations of GM-CSF (<0...
June 28, 2018: Cellular Signalling
Liu Liu, Hua Long, Yan Wu, Hui Li, Ling Dong, Julia Li Zhong, Zhaojian Liu, Xiaolong Yang, Xiaotian Dai, Lei Shi, Maozhi Ren, Zhenghong Lin
The tyrosine phosphatases family member PTEN is a tumor suppressor which is widely expressed throughout the body and is involved in a variety of biological functions. PTEN is known to be frequently mutated or downregulated in human cancers. However, the underlying molecular mechanism remains largely unknown. Here, using a proteomic approach, we identified the E3 ubiquitin ligase HRD1, which was previously reported to be involved in endoplasmic reticulum associated degradation (ERAD), as one of the PTEN-interacting proteins...
June 26, 2018: Cellular Signalling
Chunyan Zhang, Cuifang Chang, Hang Gao, Qiwen Wang, Fuchun Zhang, Cunshuan Xu
Increasing evidence indicates that miR-429 is involved in tumor suppression in various human cancers. However, its role in liver regeneration remains unexplored. Liver regeneration is a highly orchestrated process that can be regulated by microRNAs (miRNAs), although the mechanisms are largely unclear. In this study, we aimed to identify the role of miR-429 in hepatocyte proliferation during liver regeneration. First, we performed microarray analysis and qRT-PCR. Results indicated that miR-429 level in rat liver markedly decreased 30 h after partial hepatectomy, and miR-429 overexpression disrupted BRL-3A proliferation and the transition of G1 to S phase in rat hepatocyte and promoted hepatocyte apoptosis...
June 26, 2018: Cellular Signalling
Cameron S Brand, Valerie P Tan, Joan Heller Brown, Shigeki Miyamoto
Cardiac ischemia/reperfusion, loss of blood flow and its subsequent restoration, causes damage to the heart. Oxidative stress from ischemia/reperfusion leads to dysfunction and death of cardiomyocytes, increasing the risk of progression to heart failure. Alterations in mitochondrial dynamics, in particular mitochondrial fission, have been suggested to play a role in cardioprotection from oxidative stress. We tested the hypothesis that activation of RhoA regulates mitochondrial fission in cardiomyocytes. Our studies show that expression of constitutively active RhoA in cardiomyocytes increases phosphorylation of Dynamin-related protein 1 (Drp1) at serine-616, and leads to localization of Drp1 at mitochondria...
June 25, 2018: Cellular Signalling
Lizzy Wanka, Stefanie Babilon, Anette Kaiser, Karin Mörl, Annette G Beck-Sickinger
GPCR internalization, which is induced by arrestin recruitment, is an important mechanism for the regulation of signaling and receptor quantity at the cell surface. In this study, differences in the mechanism of arrestin-3 (arr-3) recruitment to the neuropeptide Y1 and Y2 receptor were identified. These receptors play an essential role in the regulation of feeding, energy homeostasis and cancer. The Y1 R displays high affinity to arr-3, which induces rapid internalization of the arrestin/receptor complex. In contrast, the Y2 R has a lower affinity for arr-3...
June 23, 2018: Cellular Signalling
Kazem Zibara, Asad Zeidan, Khalil Mallah, Nouhad Kassem, Ali Awwad, Frédéric Mazurier, Bassam Badran, Nabil El-Zein
PACAP has opposing roles ranging from activation to inhibition of tumor growth and PACAP agonists/antagonists could be used in tumor therapy. In this study, the effect of PACAP stimulation on signaling pathways was investigated in MCF-7 human adenocarcinoma breast cancer cells. Results showed that MCF-7 cells express VPAC1 and VPAC2, but not PAC1, receptors. In addition, PACAP increased the phosphorylation levels of STAT1, Src and Raf within seconds, confirming their involvement in early stages of PACAP signaling whereas maximal phosphorylation of AKT, ERK and p38 was reached 10 to 20 min later...
June 20, 2018: Cellular Signalling
Kathleen Watt, Daniel Newsted, Elena Voorand, Robert J Gooding, Adrianna Majewski, Peter Truesdell, Binchen Yao, Thomas Tuschl, Neil Renwick, Andrew W Craig
MicroRNA-206 (miR-206) has demonstrated tumor suppressive effects in a variety of cancers. Numerous studies have identified aberrantly expressed targets of miR-206 that contribute to tumor progression and metastasis, however, the broader gene-networks and pathways regulated by miR-206 remain poorly defined. Here, we have ectopically expressed miR-206 in lung adenocarcinoma cell lines and tumors to identify differentially expressed genes, and study the effects on tumor growth and metastasis. In H1299 tumor xenograft assays, stable expression of miR-206 suppressed both tumor growth and metastasis in mice...
June 20, 2018: Cellular Signalling
Ibragim Gaidarov, John Adams, John Frazer, Todd Anthony, Xiaohua Chen, Joel Gatlin, Graeme Semple, David J Unett
Angiotensin (1-7) has been reported to be a ligand for the GPCR MAS1. Small molecule MAS1 modulators have also been recently characterized. Aside from convincing evidence for MAS1 activation of Gq signaling, little is known about MAS1 mediated signaling pathways initiated by these ligands, especially Ang (1-7). We performed a comprehensive characterization of recombinant MAS1 signaling induced by Ang (1-7) and small molecule ligands through numerous G protein-dependent and independent pathways, and in a signaling pathway agnostic approach...
June 18, 2018: Cellular Signalling
Jiali Zhang, Zuo Wang, Siwei Zhang, Yanxun Chen, Xuexue Xiong, Xiaojuan Li, Nicholas K Tonks, Gaofeng Fan
A critical aspect of understanding the regulation of signal transduction is not only to identify the protein-protein interactions that govern assembly of signaling pathways, but also to understand how those pathways are regulated in time and space. In this report, we have applied both gain-of-function and loss-of-function analyses to assess the role of the non-receptor protein tyrosine kinase FER in activation of the HGF Receptor protein tyrosine kinase MET. Overexpression of FER led to direct phosphorylation of several signaling sites in MET, including Tyr1349, but not the activation loop residues Tyr1234/5; in contrast, suppression of FER by RNAi revealed that phosphorylation of both a C-terminal signaling site (Tyr1349) and the activation loop (Tyr1234/5) were influenced by the function of this kinase...
June 16, 2018: Cellular Signalling
Yong Li, Shengping Huang, Xuan Huang, Xiuzhen Li, Adrian Falcon, Adele Soutar, Frederic Bornancin, Zhisheng Jiang, Hong-Bo Xin, Mingui Fu
Mucosa associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is not only an intracellular signaling scaffold protein but also a paracaspase that plays a key role in the signal transduction and cellular activation of lymphocytes and macrophages. However, its role in endothelial cells remains unknown. Here we report that pharmacological inhibition of MALT1 protease activity strongly suppresses endothelial activation via enhancing MCPIP1 expression. Treatment with MALT1 protease inhibitors selectively inhibited TNFα-induced VCAM-1 expression in HUVECs and LPS-induced VCAM-1 expression in mice...
June 15, 2018: Cellular Signalling
Banrida Wahlang, Craig McClain, Shirish Barve, Leila Gobejishvili
Liver disease is a significant health problem worldwide with mortality reaching around 2 million deaths a year. Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are the major causes of chronic liver disease. Pathologically, NAFLD and ALD share similar patterns of hepatic disorders ranging from simple steatosis to steatohepatitis, fibrosis and cirrhosis. It is becoming increasingly important to identify new pharmacological targets, given that there is no FDA-approved therapy yet for either NAFLD or ALD...
June 11, 2018: Cellular Signalling
Ronghua Li, Meng Qiao, Xintong Zhao, Jianjun Yan, Xiaoyan Wang, Qing Sun
Psoriasis is a common immune-mediated chronic inflammatory skin disease characterized by abnormal keratinocyte proliferation, differentiation and apoptosis. However, the exact etiology and pathogenesis are still unclear. Evidence is rapidly accumulating for the role of microRNAs in psoriasis. It has been demonstrated that Interleukin-22 (IL-22) plays vital role in T cell-mediated immune response by interacting with keratinocytes in the pathogenesis of psoriasis. The aim of our study was to explore the possible functional role of miR-20a-3p in psoriasis and in IL-22 induced keratinocyte proliferation...
June 7, 2018: Cellular Signalling
Qiang Fu, Fan Yang, Ji Zhao, Xingxing Yang, Tengxiao Xiang, Guoli Huai, Jiashu Zhang, Liang Wei, Shaoping Deng, Hongji Yang
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. It has been previously reported that CSN5 depletion is an effective method in human HCC. In the current study, we aimed to uncover gene signatures and key pathways during HCC. Gene expression profiles of GSE26485 were downloaded from GEO database. Totally, 101 differentially expressed genes (DEGs) were up-regulated and 146 ones were down-regulated. Biological processes (BP) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis showed that the DEGs were mainly enriched in regulation of cell growth, oxidation-reduction process, mitotic cytokinesis, negative regulation of macroautophagy, endosome organization, lysosome, biosynthesis of antibiotics, small cell lung cancer and glutathione metabolism and so on (P < 0...
June 6, 2018: Cellular Signalling
Bongjun Kim, Jong-Ho Lee, Won Jong Jin, Hong-Hee Kim, Hyunil Ha, Zang Hee Lee
Platelet-derived growth factor receptor (PDGFR) signaling has been shown to inhibit osteogenesis. However, therapeutic efficacy of inhibiting PDGF signaling to bone regeneration in vivo and the specific mechanisms by which PDGFR signaling inhibits osteogenic differentiation remain unclear. In the present study, we examined the osteogenic effect of inhibiting PDGFR using trapidil, a PDGFR antagonist, in vivo and in vitro, and evaluated its mechanisms. A rat calvarial defect model was analyzed by micro-computed tomography and histology to determine the pro-osteogenic effect of trapidil in vivo...
June 4, 2018: Cellular Signalling
Subu Surendran Rajasekaran, Jaeyoon Kim, Gian-Carlo Gaboardi, Jesper Gromada, Stephen B Shears, Karen Tiago Dos Santos, Eduardo Lima Nolasco, Sabrina de Souza Ferreira, Christopher Illies, Martin Köhler, Chunfang Gu, Sung Ho Ryu, Joilson O Martins, Elisabetta Darè, Christopher J Barker, Per-Olof Berggren
No abstract text is available yet for this article.
May 25, 2018: 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
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
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