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https://www.readbyqxmd.com/read/29161318/loss-of-mtorc2-signaling-in-oligodendrocyte-precursor-cells-delays-myelination
#1
Mark D Grier, Kathryn L West, Nathaniel D Kelm, Cary Fu, Mark D Does, Brittany Parker, Eleanor McBrier, Andre H Lagrange, Kevin C Ess, Robert P Carson
Myelin abnormalities are increasingly being recognized as an important component of a number of neurologic developmental disorders. The integration of many signaling pathways and cell types are critical for correct myelinogenesis. The PI3-K and mechanistic target of rapamycin (mTOR) pathways have been found to play key roles. mTOR is found within two distinct complexes, mTORC1 and mTORC2. mTORC1 activity has been shown to play a major role during myelination, while the role of mTORC2 is not yet well understood...
2017: PloS One
https://www.readbyqxmd.com/read/29156676/uncoupling-torc2-from-agc-kinases-inhibits-tumour-growth
#2
Angus J M Cameron, Selvaraju Veeriah, Jacqueline J T Marshall, Elizabeth R Murray, Banafshé Larijani, Peter J Parker
Mammalian target of rapamycin (mTOR) is a central regulator of growth and metabolism. mTOR resides in two distinct multi-protein complexes - mTORC1 and mTORC2 - with distinct upstream regulators and downstream targets. While it is possible to specifically inhibit mTORC1 with rapamycin, or inhibit both mTOR complexes together with ATP pocket directed mTOR kinase inhibitors, it is not possible to assess the specific roles for mTORC2 pharmacologically. To overcome this, we have developed a novel, inducible, dominant negative system for disrupting substrate recruitment to mTORC2...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29113267/overexpression-of-rictor-protein-in-colorectal-cancer-is-correlated-with-tumor-progression-and-prognosis
#3
Lifeng Wang, Jia Qi, Jinlong Yu, Haijin Chen, Zhaowei Zou, Xiaohua Lin, Linlang Guo
In order to understand the clinical significance of rapamycin-insensitive companion of mammalian target of rapamycin (Rictor) in colorectal cancer (CRC), 62 CRC tissue samples excised during operations were evaluated by immunohistochemistry. Analysis of the association between the expression level of Rictor protein and clinicopathological parameters demonstrated that the expression level of Rictor in CRC tissues was significantly higher than that in paracarcinoma tissues (P<0.0001). In cellular experiments, this result was further confirmed by comparing differences in Rictor expression between the CRC cell lines HCT116, SW480 and LoVo, and the human normal liver cell line HL-7702...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29104218/evolutionary-conservation-of-the-components-in-the-tor-signaling-pathways
#4
REVIEW
Hisashi Tatebe, Kazuhiro Shiozaki
Target of rapamycin (TOR) is an evolutionarily conserved protein kinase that controls multiple cellular processes upon various intracellular and extracellular stimuli. Since its first discovery, extensive studies have been conducted both in yeast and animal species including humans. Those studies have revealed that TOR forms two structurally and physiologically distinct protein complexes; TOR complex 1 (TORC1) is ubiquitous among eukaryotes including animals, yeast, protozoa, and plants, while TOR complex 2 (TORC2) is conserved in diverse eukaryotic species other than plants...
November 1, 2017: Biomolecules
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
#5
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/29077002/the-role-of-mammalian-target-of-rapamycin-mtor-in-insulin-signaling
#6
REVIEW
Mee-Sup Yoon
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that controls a wide spectrum of cellular processes, including cell growth, differentiation, and metabolism. mTOR forms two distinct multiprotein complexes known as mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), which are characterized by the presence of raptor and rictor, respectively. mTOR controls insulin signaling by regulating several downstream components such as growth factor receptor-bound protein 10 (Grb10), insulin receptor substrate (IRS-1), F-box/WD repeat-containing protein 8 (Fbw8), and insulin like growth factor 1 receptor/insulin receptor (IGF-IR/IR)...
October 27, 2017: Nutrients
https://www.readbyqxmd.com/read/29072256/rapamycin-inhibits-ox-ldl-induced-inflammation-in-human-endothelial-cells-in-vitro-by-inhibiting-the-mtorc2-pkc-c-fos-pathway
#7
Juan-Juan Sun, Xiao-Wei Yin, Hui-Hui Liu, Wen-Xiu Du, Lu-Yao Shi, Ya-Bo Huang, Fen Wang, Chun-Feng Liu, Yong-Jun Cao, Yan-Lin Zhang
Rapamycin and its derivative possess anti-atherosclerosis activity, but its effects on adhesion molecule expression and macrophage adhesion to endothelial cells during atherosclerosis remain unclear. In this study we explored the effects of rapamycin on ox-LDL-induced adhesion molecule expression and macrophage adhesion to endothelial cells in vitro and the underlying mechanisms. Ox-LDL (6-48 μg/mL) dose-dependently increased the protein levels of two adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and E-selectin, in human umbilical vein endothelial cells (HUVECs), whereas pretreatment with rapamycin (1-10 μmol/L) dose-dependently inhibited ox-LDL-induced increase in the adhesion molecule expression and macrophage adhesion to endothelial cells...
October 26, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29070461/-rictor-mtorc2-regulates-blood-testis-barrier-and-spermatogenesis-in-mice
#8
He-Ling Dong, Hong-Yuan Wu, You Fu, Meng Dai, Xiao-Chun Bai, Hong Wang
OBJECTIVE: To investigate the role of Rictor/mTORC2 in the formation of blood testis barrier (BTB), testicular development, and spermatogenesis. METHODS: Amh Cre positive mice homozygous for rictor loxP with Sertoli cell specific deletion of rictor were obtained by cross breeding Amh Cre mice with rictor loxP mice. The histology of the reproductive organs, seminiferous tubules and epididymis of the transgenic mice was observed with HE staining. The cell subgroups of the germ cells in the seminiferous tubule were detected by flow cytometry with propidium iodide labeling...
October 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/29059166/mtorc2-akt-hsf1-hur-constitute-a-feed-forward-loop-regulating-rictor-expression-and-tumor-growth-in-glioblastoma
#9
B Holmes, A Benavides-Serrato, R S Freeman, K A Landon, T Bashir, R N Nishimura, J Gera
Overexpression of Rictor has been demonstrated to result in increased mechanistic target of rapamycin C2 (mTORC2) nucleation and activity leading to tumor growth and increased invasive characteristics in glioblastoma multiforme (GBM). However, the mechanisms regulating Rictor expression in these tumors is not clearly understood. In this report, we demonstrate that Rictor is regulated at the level of mRNA translation via heat-shock transcription factor 1 (HSF1)-induced HuR activity. HuR is shown to directly bind the 3' untranslated region of the Rictor transcript and enhance translational efficiency...
October 23, 2017: Oncogene
https://www.readbyqxmd.com/read/29019056/physical-exercise-modulates-l-dopa-regulated-molecular-pathways-in-the-mptp-mouse-model-of-parkinson-s-disease
#10
Cornelius J H M Klemann, Helena Xicoy, Geert Poelmans, Bas R Bloem, Gerard J M Martens, Jasper E Visser
Parkinson's disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), resulting in motor and non-motor dysfunction. Physical exercise improves these symptoms in PD patients. To explore the molecular mechanisms underlying the beneficial effects of physical exercise, we exposed 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine (MPTP)-treated mice to a four-week physical exercise regimen, and subsequently explored their motor performance and the transcriptome of multiple PD-linked brain areas...
October 10, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28986255/down-regulation-of-peroxiredoxin-3-in-3t3-l1-adipocytes-leads-to-oxidation-of-rictor-in-the-mammalian-target-of-rapamycin-complex-2-mtorc2
#11
Dalay H Olson, Joel S Burrill, Jovan Kuzmicic, Wendy S Hahn, Ji-Man Park, Do-Hyung Kim, David A Bernlohr
Mitochondrially-derived oxidative stress has been implicated in the development of obesity-induced insulin resistance and is correlated with down regulation of Peroxiredoxin-3 (Prdx3). Prdx3 knockout mice exhibit whole-body insulin resistance, while Prdx3 transgenic animals remain insulin sensitive when placed on a high fat diet. To define the molecular events linking mitochondrial oxidative stress to insulin action, Prdx3 was silenced in 3T3-L1 adipocytes (Prdx3 KD) and the resultant cells evaluated for mitochondrial function, endoplasmic reticulum stress (ER stress), mitochondrial unfolded protein response (mtUPR) and insulin signaling...
November 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28979705/targeting-mtorc2-component-rictor-inhibits-cell-proliferation-and-promotes-apoptosis-in-gastric-cancer
#12
Yu-Hai Bian, Jia Xu, Wen-Yi Zhao, Zi-Zhen Zhang, Lin Tu, Hui Cao, Zhi-Gang Zhang
The mammalian target of rapamycin (mTOR) kinase acts downstream of phosphoinositide 3-kinase/Akt and plays an important role in tumor growth and progression of gastric cancer. It is well characterized that mTOR complex1 (mTORC1) controls cell metabolism and proliferation, whereas the contribution of mTOR complex2 (mTORC2) and its key component, Rictor, remains poorly understood. Therefore, we investigated clinical significance of Rictor expression by immunohistochemical analysis of 391 tissue samples from gastric cancer patients...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28971834/differential-localisation-and-anabolic-responsiveness-of-mtor-complexes-in-human-skeletal-muscle-in-response-to-feeding-and-exercise
#13
Nathan Hodson, Chris McGlory, Sara Y Oikawa, Stewart Jeromson, Zhe Song, Markus A Ruegg, D Lee Hamilton, Stuart M Phillips, Andrew Philp
Mechanistic target of rapamycin (mTOR) resides as two complexes within skeletal muscle. mTOR complex 1 (mTORC1-Raptor positive) regulates skeletal muscle growth, whereas mTORC2 (Rictor positive) regulates insulin sensitivity. To examine the regulation of these complexes in human skeletal muscle, we utilised immunohistochemical analysis to study the localisation of mTOR complexes prior to and following protein-carbohydrate feeding (FED) and resistance exercise plus protein-carbohydrate feeding (EXFED) in unilateral exercise model...
September 27, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28968999/association-of-msin1-with-mtorc2-ras-and-akt-reveals-a-crucial-domain-on-msin1-involved-in-akt-phosphorylation
#14
Chien-An Yao, Sara Ortiz-Vega, Yun-Ya Sun, Chiang-Ting Chien, Jen-Hua Chuang, Yenshou Lin
mSin1 is a unique component within the mammalian target of rapamycin (mTOR) complex 2 (mTORC2), which is responsible for cellular morphology and glucose metabolism. The association between mSin1 and other mTORC2 components, as well as their functions, has been explored previously; nevertheless, the mapping of the various binding domains of the components is lacking. Based on an evolutionary analysis of the gene, we constructed various fragments and truncated-forms of mSin1. We characterized the individual binding sites of mSin1 with its various partners, including mTOR, Rictor, Ras, and Akt...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28953980/influenza-virus-differentially-activates-mtorc1-and-mtorc2-signaling-to-maximize-late-stage-replication
#15
Sharon K Kuss-Duerkop, Juan Wang, Ignacio Mena, Kris White, Giorgi Metreveli, Ramanavelan Sakthivel, Miguel A Mata, Raquel Muñoz-Moreno, Xiang Chen, Florian Krammer, Michael S Diamond, Zhijian J Chen, Adolfo García-Sastre, Beatriz M A Fontoura
Influenza A virus usurps host signaling factors to regulate its replication. One example is mTOR, a cellular regulator of protein synthesis, growth and motility. While the role of mTORC1 in viral infection has been studied, the mechanisms that induce mTORC1 activation and the substrates regulated by mTORC1 during influenza virus infection have not been established. In addition, the role of mTORC2 during influenza virus infection remains unknown. Here we show that mTORC2 and PDPK1 differentially phosphorylate AKT upon influenza virus infection...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28946557/rituximab-effectively-reverses-tyrosine-kinase-inhibitors-tkis-resistance-through-inhibiting-the-accumulation-of-rictor-on-mitochondria-associated-er-membrane-mam
#16
Zhi-Hong Xu, Cai-Hong Liu, Jun-Biao Hang, Bei-Li Gao, Jia-An Hu
Tyrosine kinase inhibitors (TKIs), a novel group of target-specific anti lung cancer drugs, have recently been found to resistant to some NSCLC cells which have the T790M EGFR mutation. However, recent investigations on the therapies of resistance to EGFR-TKIs are very limited. Therefore, it is important to develop more effective therapies to reverse EGFR-TKIs resistance. In our present study, erlotinib was used as the TKIs drug and the effects of the erlotinib on cell growth were evaluated. Cell viability and concentration dependent studies were performed using HCI-H1975 and HCI-H1299 cells alone with erlotinib, respectively...
September 15, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28930662/the-kinase-mtorc1-promotes-the-generation-and-suppressive-function-of-follicular-regulatory-t-cells
#17
Lifan Xu, Qizhao Huang, Haoqiang Wang, Yaxing Hao, Qiang Bai, Jianjun Hu, Yiding Li, Pengcheng Wang, Xiangyu Chen, Ran He, Bingshou Li, Xia Yang, Tingting Zhao, Yanyan Zhang, Yifei Wang, Juanjuan Ou, Houjie Liang, Yuzhang Wu, Xinyuan Zhou, Lilin Ye
Follicular regulatory T (Tfr) cells differentiate from conventional regulatory T (Treg) cells and suppress excessive germinal center (GC) responses by acting on both GC B cells and T follicular helper (Tfh) cells. Here, we examined the impact of mTOR, a serine/threonine protein kinase that senses and integrates diverse environmental cues, on the differentiation and functional competency of Tfr cells in response to protein immunization or viral infection. By genetically deleting Rptor or Rictor, essential components for mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), respectively, we found that mTORC1 but not mTORC2 is essential for Tfr differentiation...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28888905/selective-interference-of-mtorc1-raptor-protects-against-human-disc-cellular-apoptosis-senescence-and-extracellular-matrix-catabolism-with-akt-and-autophagy-induction
#18
M Ito, T Yurube, K Kakutani, K Maeno, T Takada, Y Terashima, Y Kakiuchi, Y Takeoka, S Miyazaki, R Kuroda, K Nishida
OBJECTIVE: The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that integrates nutrients to execute cell growth and protein synthesis. We hypothesized that mTOR is essential for the intervertebral disc, the largest avascular, low-nutrient organ. Our objective was to elucidate roles of mTOR signaling in human disc cells. DESIGN: The mTOR exists in two complexes: mTORC1 containing the regulatory-associated protein of mTOR (RAPTOR) and mTORC2 containing the rapamycin-insensitive companion of mTOR (RICTOR)...
September 6, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28860410/next-generation-sequencing-for-patients-with-sarcoma-a-single-center-experience
#19
Gregory M Cote, Jie He, Edwin Choy
BACKGROUND: Sarcomas comprise over 50 subtypes of mesenchymal cancers. For the majority of sarcomas, the driver mutations remain unknown. In this article, we describe our experience with a targeted next-generation sequencing (NGS) platform in clinic patients. MATERIALS AND METHODS: We retrospectively analyzed results of NGS using 133 tumor samples from patients diagnosed with a variety of sarcomas that were analyzed with targeted NGS covering over 400 cancer-related genes (405 DNA, 265 RNA) on a commercially available platform...
August 31, 2017: Oncologist
https://www.readbyqxmd.com/read/28821013/rictor-positively-regulates-b-cell-receptor-signaling-by-modulating-actin-reorganization-via-ezrin
#20
Lu Huang, Yongjie Zhang, Chenguang Xu, Xiaomei Gu, Linlin Niu, Jinzhi Wang, Xiaoyu Sun, Xiaoming Bai, Xingtian Xuan, Qubei Li, Chunwei Shi, Bing Yu, Heather Miller, Gangyi Yang, Lisa S Westerberg, Wanli Liu, Wenxia Song, Xiaodong Zhao, Chaohong Liu
As the central hub of the metabolism machinery, the mammalian target of rapamycin complex 2 (mTORC2) has been well studied in lymphocytes. As an obligatory component of mTORC2, the role of Rictor in T cells is well established. However, the role of Rictor in B cells still remains elusive. Rictor is involved in B cell development, especially the peripheral development. However, the role of Rictor on B cell receptor (BCR) signaling as well as the underlying cellular and molecular mechanism is still unknown. This study used B cell-specfic Rictor knockout (KO) mice to investigate how Rictor regulates BCR signaling...
August 2017: PLoS Biology
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