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phosphatase signalling

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https://www.readbyqxmd.com/read/28548966/targeting-shp-1-stat3-signaling-a-promising-therapeutic-approach-for-the-treatment-of-cholangiocarcinoma
#1
Ming-Hung Hu, Li-Ju Chen, Yen-Lin Chen, Ming-Shen Tsai, Chung-Wai Shiau, Tzu-I Chao, Chun-Yu Liu, Jia-Horng Kao, Kuen-Feng Chen
Sorafenib is a multiple kinase inhibitor which targets Raf kinases, VEGFR, and PDGFR and is approved for the treatment of hepatocellular carcinoma (HCC). Previously, we found that p-STAT3 is a major target of SC-43, a sorafenib derivative. In this study, we report that SC-43-induced apoptosis in cholangiocarcinoma (CCA) via a novel mechanism. Three CCA cell lines (HuCCT-1, KKU-100 and CGCCA) were treated with SC-43 to determine their sensitivity to SC-43-induced cell death and apoptosis. We found that SC-43 activated SH2 domain-containing phosphatase 1 (SHP-1) activity, leading to p-STAT3 and downstream cyclin B1 and Cdc2 downregulation, which induced G2-M arrest and apoptotic cell death...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548879/ras-and-rho-gtpase-regulation-of-pol-ii-transcription-a-shortcut-model-revisited
#2
Zhi-Liang Zheng
Transcriptional control is critical in relaying signals mediated by Ras and Rho family small GTPases to effect gene expression. In the classical model, signaling components such as MAP kinase target sequence-specific transcription factors, which in turn recruit RNA polymerase (Pol) II holoenzyme to the promoter and activate transcription. Findings in recent years have led to the proposal of a shortcut model in which the mediator components of the Pol II holoenzyme are regulated by signaling pathways. A very recent finding shows that an evolutionarily conserved Rho GTPase signaling pathway can directly modulate the Pol II C-terminal domain (CTD) phosphorylation by inhibiting the CTD phosphatase in yeast and Arabidopsis...
May 26, 2017: Transcription
https://www.readbyqxmd.com/read/28548306/zanthoxylum-avicennae-extract-enhances-gsk-3%C3%AE-to-attenuate-%C3%AE-catenin-via-phosphatase-2a-to-block-metastatic-effects-of-ha22t-cells-and-hepatocellular-carcinoma-xenografted-nude-mice
#3
Hsi-Chin Wu, Ing-Shiow Lay, Marthandam Asokan Shibu, Tsung-Jung Ho, Shiu-Min Cheng, Chih-Hao Lin, Tran Duc Dung, Long-Bin Jeng, Vijaya Padma Viswanadha, Chih-Yang Huang
Hepatocellular carcinoma (HCC) metastasis is often associated with the activation of Wnt/β-catenin signaling pathway. Zanthoxylum avicennae (Ying Bu Bo, YBB), a traditional herb with hepatoprotective effect, has been proven to inhibit human HCC in in vivo models however, the in vitro and in vivo effect of YBB on tumor metastasis is not clear yet. To determine whether YBB could inhibit HA22T human HCC cell by acting on β-catenin metastatic signaling in vitro and in vivo, HA22T cells were treated with different concentrations of YBB extracts (YBBE) and analyzed by Immunofluorescence staining assay, western blot analysis, siRNA mediated gene knock-down assays and co-immunoprecipitation assay...
May 26, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28546021/sodium-butyrate-improved-intestinal-immune-function-associated-with-nf-%C3%AE%C2%BAb-and-p38mapk-signalling-pathways-in-young-grass-carp-ctenopharyngodon-idella
#4
Li Tian, Xiao-Qiu Zhou, Wei-Dan Jiang, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Fei Xie, Lin Feng
The present study evaluated the effect of dietary sodium butyrate (SB) supplementation on the growth and immune function in the proximal intestine (PI), middle intestine (MI) and distal intestine (DI) of young grass carp (Ctenopharyngodon idella). The fish were fed one powdery sodium butyrate (PSB) diet (1000.0 mg kg(-1) diet) and five graded levels of microencapsulated sodium butyrate (MSB) diets: 0.0 (control), 500.0, 1000.0, 1500.0 and 2000.0 mg kg(-1) diet for 60 days. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila...
May 22, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28544778/differential-regulation-of-protein-tyrosine-kinase-signaling-by-dock-and-the-ptp61f-variants
#5
Lee F Willoughby, Jan Manent, Kirsten Allan, Han Lee, Marta Portela, Florian Wiede, Coral Warr, Tzu-Ching Meng, Tony Tiganis, Helena E Richardson
Tyrosine phosphorylation-dependent signalling is coordinated by the opposing actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). There is a growing list of adaptor proteins that interact with PTPs and facilitate the dephosphorylation of substrates. The extent to which any given adaptor confers selectivity for any given substrate in vivo remains unclear. Here we have taken advantage of Drosophila melanogaster as a model organism to explore the influence of the SH3/SH2 adaptor protein Dock on the abilities of the membrane (PTP61Fm)- and nuclear (PTP61Fn)-targeted variants of PTP61F (the Drosophila othologue of the mammalian enzymes PTP1B and TCPTP respectively) to repress PTK signaling pathways in vivo...
May 23, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28542923/the-polysialic-acid-mimetics-idarubicin-and-irinotecan-stimulate-neuronal-survival-and-neurite-outgrowth-and-signal-via-protein-kinase-c
#6
Gabriele Loers, Steven Astafiev, Yuliya Hapiak, Vedangana Saini, Bibhudatta Mishra, Sheraz Gul, Gurcharan Kaur, Melitta Schachner, Thomas Theis
Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues. It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule NCAM. PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions...
May 24, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28542730/estrogen-receptor-%C3%AE-regulates-the-tumoral-suppressor-pten-to-modulate-pituitary-cell-growth
#7
Pablo Anibal Perez, Juan Pablo Petiti, Florencia Picech, Carolina Beatriz Guido, Liliana Del Valle Sosa, Ezequiel Grondona, Jorge Humberto Mukdsi, Ana Lucia De Paul, Alicia Ines Torres, Silvina Gutierrez
In this study, we focused on ERβ regulation in the adenohypophysis under different estrogenic milieu, by analyzing whether ER modulates the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) expression and its subcellular localization on anterior pituitary glands from Wistar rats and GH3 lactosomatotroph cells that over-expressed ERβ. ERβ was regulated in a cyclic manner, and underwent dynamic changes throughout the estrous cycle, with decreased ERβ+ cells in estrus and under E2 treatment, but increased in ovariectomized rats...
May 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28542134/phosphorylated-cav1-activates-autophagy-through-an-interaction-with-becn1-under-oxidative-stress
#8
Jihoon Nah, Seung-Min Yoo, Sunmin Jung, Eun Il Jeong, Moonju Park, Bong-Kiun Kaang, Yong-Keun Jung
CAV1/Caveolin1, an integral membrane protein, is involved in caveolae function and cellular signaling pathways. Here, we report that CAV1 is a positive regulator of autophagy under oxidative stress and cerebral ischemic injury. Treatment with hydrogen peroxide enhanced autophagy flux and caused the localization of BECN1 to the mitochondria, whereas these changes were impaired in the absence of CAV1. Among many autophagy signals, only LC3 foci formation in response to hydrogen peroxide was abolished by CAV1 deficiency...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28541680/regulatory-mechanisms-and-novel-therapeutic-targeting-strategies-for-protein-tyrosine-phosphatases
#9
Zhi-Hong Yu, Zhong-Yin Zhang
An appropriate level of protein phosphorylation on tyrosine is essential for cells to react to extracellular stimuli and maintain cellular homeostasis. Faulty operation of signal pathways mediated by protein tyrosine phosphorylation causes numerous human diseases, which presents enormous opportunities for therapeutic intervention. While the importance of protein tyrosine kinases in orchestrating the tyrosine phosphorylation networks and in target-based drug discovery has long been recognized, the significance of protein tyrosine phosphatases (PTPs) in cellular signaling and disease biology has historically been underappreciated, due to a large extent to an erroneous assumption that they are largely constitutive and housekeeping enzymes...
May 25, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28539364/integrative-proteomics-and-biochemical-analyses-define-ptc6p-as-the-saccharomyces-cerevisiae-pyruvate-dehydrogenase-phosphatase
#10
Xiao Guo, Natalie M Niemi, Joshua J Coon, Dave J Pagliarini
The pyruvate dehydrogenase complex (PDC) is the primary metabolic checkpoint connecting glycolysis and mitochondrial oxidative phosphorylation, and is important for maintaining cellular and organismal glucose homeostasis. Phosphorylation of the PDC E1 subunit was identified as a key inhibitory modification in bovine tissue approximately 50 years ago, and this regulatory process is now known to be conserved throughout evolution. Although Saccharomyces cerevisiae is a pervasive model organism for investigating cellular metabolism and its regulation by signaling processes, the phosphatase(s) responsible for activating the PDC in S...
May 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28537241/-fibroblast-growth-factor-receptor-1-propagates-estrogen-and-fluid-shear-stress-driven-proliferation-and-differentiation-response-in-mc3t3-e1-cells
#11
J Y Li, S G Liu, G N Xiao, M Y Mao, X W Zhang, H Q Sun
Fluid shear stress (FSS) and estrogen exposure positively regulate bone metabolism. Fibroblast growth factor receptor 1 (FGFR1) plays a vital role in FSS-induced osteogenesis. An in vitro experiment with MC3T3-E1 cells combined with microarray analysis aided us in identification of the genes differentially expressed in response to FSS and highlighted the role of FGFR1 in this process. Both estrogen exposure and FSS increase methyl thiazol tetrazolium (MTT) values and alkaline phosphatase (ALP) activity, as well as the levels of Runt-related transcription factor 2 (Runx2) and osteocalcin (OCN)...
March 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28536529/activation-of-sirt1-fxr-signaling-pathway-attenuates-triptolide-induced-hepatotoxicity-in-rats
#12
Jing Yang, Lixin Sun, Lu Wang, Hozeifa M Hassan, Xuan Wang, Phillip B Hylemon, Tao Wang, Huiping Zhou, Luyong Zhang, Zhenzhou Jiang
Triptolide (TP), a diterpenoid isolated from Tripterygium wilfordii Hook F, has an excellent pharmacological profile of immunosuppression and anti-tumor activities, but its clinical applications are severely restricted due to its severe and cumulative toxicities. The farnesoid X receptor (FXR) is the master bile acid nuclear receptor and plays an important role in maintaining hepatic metabolism homeostasis. Hepatic Sirtuin (Sirt1) is a key regulator of the FXR signaling pathway and hepatic metabolism homeostasis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28536031/lactate-induces-osteoblast-differentiation-by-stabilization-of-hif1%C3%AE
#13
Yu Wu, Miaomiao Wang, Haihua Feng, Ying Peng, Jieyun Sun, Xiuxia Qu, Chunping Li
Aerobic glycolysis is involved in osteoblast differentiation induced by Wnt signaling or PTH treatment. However, it is still unclear whether lactate, the end product of aerobic glycolysis, plays any role in osteoblast differentiation. Herein we report that in cultures of osteoblast-lineage cells, lactate promoted alkaline phosphatase-positive cell formation, increased the activity of alkaline phosphatase, and induced the expression of osteocalcin. This osteoblast differentiation-inducing effect of lactate can be inhibited by blocking its entry into cells with MCT1 siRNA or inhibitors, and by interfering with its metabolism by using specific siRNAs for LDHB and PDH...
May 20, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28535647/-effects-of-overexpression-of-mir-17-92-gene-cluster-on-the-biological-characteristics-of-prostate-cancer-cells-and-its-mechanism
#14
P Zhou, L Ma, J Zhou, J J Xu, F Liu, F Guo
Objective: To explore the effect and mechanism of over-expression of miR-17-92 gene cluster on the biological characteristics of prostate cancer cells. Methods: DU145 cells were transfected with miR-17-92 gene expression plasmid and clones with stable ectopic miR-17-92 overexpression were established. The cell viabilities of DU145-17-92 and DU145-control cells were monitored by xCELLigence system. Cell proliferation and apoptosis were analyzed by Ki-67 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay...
May 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28534995/low%C3%A2-level-mechanical-vibration-enhances-osteoblastogenesis-via-a-canonical-wnt-signaling%C3%A2-associated-mechanism
#15
Heqi Gao, Mingming Zhai, Pan Wang, Xuhui Zhang, Jing Cai, Xiaofei Chen, Guanghao Shen, Erping Luo, Da Jing
Osteoporosis is a skeletal metabolic disease characterized by reduced bone mass and a high susceptibility to fractures, in which osteoblasts and osteoclasts are highly involved in the abnormal bone remodeling processes. Recently, low‑magnitude, high‑frequency whole‑body vibration has been demonstrated to significantly reduce osteopenia experimentally and clinically. However, the underlying mechanism regarding how osteoblastic activity is altered when bone tissues adapt to mechanical vibration remains elusive...
May 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28534966/microrna-92a-promotes-epithelial-mesenchymal-transition-through-activation-of-pten-pi3k-akt-signaling-pathway-in-non-small-cell-lung-cancer-metastasis
#16
Chaojing Lu, Zhengxiang Shan, Jiang Hong, Lixin Yang
MicroRNAs (miRNAs) have important roles in various cancers, including non-small cell lung cancer (NSCLC). Although several miRNAs have reported to be involved in the development of NSCLC, understanding the regulatory roles of other miRNAs in NSCLC is essential. Therefore, the aim of the current study was to explore the roles and mechanisms of screened miRNAs in NSCLC. First, the differentially expressed miRNAs that were screened based on GSE29248 microarray data retrieved from Gene Expression Omnibus (GEO)...
May 16, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28534965/cucurbitacin%C3%A2-b-induces-autophagy-and-apoptosis-by-suppressing-cip2a-pp2a-mtorc1-signaling-axis-in-human-cisplatin-resistant-gastric-cancer-cells
#17
Xuewen Liu, Chao Duan, Juanli Ji, Te Zhang, Xiaoning Yuan, Yunfei Zhang, Wenjing Ma, Jingyuan Yang, Linsen Yang, Zhiguo Jiang, Huiliang Yu, Ying Liu
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of tumors including gastric cancer (GC). Mammalian target of rapamycin complex 1 (mTORC1) over-activation is detected in GC and many other cancers. Previous study found that CIP2A/mTORC1 controls cell growth and autophagy through direct association. CIP2A plays an 'oncogenic nexus' in several cancer types to participate in the tumorigenic transformation and chemoresistance. In the present study, we investigated whether Cucurbitacin B (CuB), a natural compound found in Cucurbitaceae, can be used in cisplatin (DDP)-resistant human GC cell line SGC7901/DDP...
May 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28534961/disruption-of-serine-threonine-protein-phosphatase-5-inhibits-tumorigenesis-of-urinary-bladder-cancer-cells
#18
Ming Chen, Jian-Min Lv, Jian-Qing Ye, Xin-Gang Cui, Fa-Jun Qu, Lu Chen, Xi Liu, Xiu-Wu Pan, Lin Li, Hai Huang, Qi-Wei Yang, Jie Chen, Lin-Hui Wang, Yi Gao, Dan-Feng Xu
Serine/threonine protein phosphatase 5 (PPP5C) is a member of the protein serine/threonine phosphatase family and has been shown to participate in multiple signaling cascades and tumor progression. We found that PPP5C was highly expressed in bladder cancer tissues compared to normal urothelial tissues, and positively correlated to tumor stages through ONCOMINE microarray data mining. Knockdown of PPP5C via a lentivirus-mediated short hairpin RNA (shRNA) markedly inhibited cell proliferation and colony formation...
May 16, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28534931/leucine-rich-glioma-inactivated-3-integrative-analyses-support-its-role-in-the-cytokine-network
#19
Hyun A Kim, Nyoun Soo Kwon, Kwang Jin Baek, Dong-Seok Kim, Hye-Young Yun
Leucine-rich glioma inactivated (LGI)3 is a secreted protein member of LGI family. We previously repo-rted that LGI3 was upregulated in adipose tissues from obese mice and suppressed adipogenesis through its receptor, a disintegrin and metalloproteinase domain-containing protein 23 (ADAM23). We demonstrated that LGI3 regulated tumor necrosis factor-α and adiponectin, and proposed that LGI3 may be a pro-inflammatory adipokine involved in adipose tissue inflammation. In this study, we analyzed adipokine and cytokine profiles in LGI3 knockout mice and demonstrated that multiple factors were increased or decreased in the adipose tissues and plasma of the LGI3 knockout mice...
May 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28534914/covalent-inhibition-of-protein-tyrosine-phosphatases
#20
REVIEW
Kasi Viswanatharaju Ruddraraju, Zhong-Yin Zhang
Protein tyrosine phosphatases (PTPs) are a large family of 107 signaling enzymes that catalyze the hydrolytic removal of phosphate groups from tyrosine residues in a target protein. The phosphorylation status of tyrosine residues on proteins serve as a ubiquitous mechanism for cellular signal transduction. Aberrant function of PTPs can lead to many human diseases, such as diabetes, obesity, cancer, and autoimmune diseases. As the number of disease relevant PTPs increases, there is urgency in developing highly potent inhibitors that are selective towards specific PTPs...
May 23, 2017: Molecular BioSystems
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