keyword
MENU ▼
Read by QxMD icon Read
search

Rheb

keyword
https://www.readbyqxmd.com/read/29133930/plc%C3%AE-dependent-mtor-signalling-controls-il-7-mediated-early-b-cell-development
#1
Mei Yu, Yuhong Chen, Hu Zeng, Yongwei Zheng, Guoping Fu, Wen Zhu, Ulrich Broeckel, Praful Aggarwal, Amy Turner, Geoffrey Neale, Cliff Guy, Nan Zhu, Hongbo Chi, Renren Wen, Demin Wang
The precise molecular mechanism underlying the regulation of early B cell lymphopoiesis is unclear. The PLCγ signaling pathway is critical for antigen receptor-mediated lymphocyte activation, but its function in cytokine signaling is unknown. Here we show that PLCγ1/PLCγ2 double deficiency in mice blocks early B cell development at the pre-pro-B cell stage and renders B cell progenitors unresponsive to IL-7. PLCγ pathway inhibition blocks IL-7-induced activation of mTOR, but not Stat5. The PLCγ pathway activates mTOR through the DAG/PKC signaling branch, independent of the conventional Akt/TSC/Rheb signaling axis...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29119228/macropinocytosis-mtorc1-and-cellular-growth-control
#2
REVIEW
Sei Yoshida, Regina Pacitto, Ken Inoki, Joel Swanson
The growth and proliferation of metazoan cells are driven by cellular nutrient status and by extracellular growth factors. Growth factor receptors on cell surfaces initiate biochemical signals that increase anabolic metabolism and macropinocytosis, an actin-dependent endocytic process in which relatively large volumes of extracellular solutes and nutrients are internalized and delivered efficiently into lysosomes. Macropinocytosis is prominent in many kinds of cancer cells, and supports the growth of cells transformed by oncogenic K-Ras...
November 8, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29104218/evolutionary-conservation-of-the-components-in-the-tor-signaling-pathways
#3
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/29091770/the-mtorc1-signaling-network-senses-changes-in-cellular-purine-nucleotide-levels
#4
Gerta Hoxhaj, James Hughes-Hallett, Rebecca C Timson, Erika Ilagan, Min Yuan, John M Asara, Issam Ben-Sahra, Brendan D Manning
Mechanistic (or mammalian) target of rapamycin complex 1 (mTORC1) integrates signals from growth factors and nutrients to control biosynthetic processes, including protein, lipid, and nucleic acid synthesis. We find that the mTORC1 pathway is responsive to changes in purine nucleotides in a manner analogous to its sensing of amino acids. Depletion of cellular purines, but not pyrimidines, inhibits mTORC1, and restoration of intracellular adenine nucleotides via addition of exogenous purine nucleobases or nucleosides acutely reactivates mTORC1...
October 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/29051493/variation-in-a-range-of-mtor-related-genes-associates-with-intracranial-volume-and-intellectual-disability
#5
M R F Reijnders, M Kousi, G M van Woerden, M Klein, J Bralten, G M S Mancini, T van Essen, M Proietti-Onori, E E J Smeets, M van Gastel, A P A Stegmann, S J C Stevens, S H Lelieveld, C Gilissen, R Pfundt, P L Tan, T Kleefstra, B Franke, Y Elgersma, N Katsanis, H G Brunner
De novo mutations in specific mTOR pathway genes cause brain overgrowth in the context of intellectual disability (ID). By analyzing 101 mMTOR-related genes in a large ID patient cohort and two independent population cohorts, we show that these genes modulate brain growth in health and disease. We report the mTOR activator gene RHEB as an ID gene that is associated with megalencephaly when mutated. Functional testing of mutant RHEB in vertebrate animal models indicates pathway hyperactivation with a concomitant increase in cell and head size, aberrant neuronal migration, and induction of seizures, concordant with the human phenotype...
October 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/29050215/proteomics-analysis-of-bladder-cancer-invasion-targeting-eif3d-for-therapeutic-intervention
#6
Agnieszka Latosinska, Marika Mokou, Manousos Makridakis, William Mullen, Jerome Zoidakis, Vasiliki Lygirou, Maria Frantzi, Ioannis Katafigiotis, Konstantinos Stravodimos, Marie C Hupe, Maciej Dobrzynski, Walter Kolch, Axel S Merseburger, Harald Mischak, Maria G Roubelakis, Antonia Vlahou
Patients with advanced bladder cancer have poor outcomes, indicating a need for more efficient therapeutic approaches. This study characterizes proteomic changes underlying bladder cancer invasion aiming for the better understanding of disease pathophysiology and identification of drug targets. High resolution liquid chromatography coupled to tandem mass spectrometry analysis of tissue specimens from patients with non-muscle invasive (NMIBC, stage pTa) and muscle invasive bladder cancer (MIBC, stages pT2+) was conducted...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29017169/ox-ldl-induced-microrna-155-promotes-autophagy-in-human-endothelial-cells-via-repressing-the-rheb-mtor-pathway
#7
Jinlin Lv, Lixia Yang, Ruiwei Guo, Yankun Shi, Ziwei Zhang, Jinshan Ye
BACKGROUND/AIMS: Autophagy, an evolutionary conserved biological process, is activated in cells to cope with various types of stress. MicroRNAs control several activities related to autophagy. However, the role of autophagy-related microRNAs during atherosclerosis is far from known. MicroRNA-155 was identified to be a crucial regulator of atherosclerosis. The objectives of the study were to analyze the effect of microRNA-155 on autophagic signaling and explore its mechanism in human endothelial cells under ox-LDL stress...
October 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28967557/combining-constitutively-active-rheb-expression-and-chondroitinase-promotes-functional-axonal-regeneration-after-cervical-spinal-cord-injury
#8
Di Wu, Michelle C Klaw, Theresa Connors, Nikolai Kholodilov, Robert E Burke, Marie-Pascale Côté, Veronica J Tom
After spinal cord injury (SCI), severed axons in the adult mammalian CNS are unable to mount a robust regenerative response. In addition, the glial scar at the lesion site further restricts the regenerative potential of axons. We hypothesized that a combinatorial approach coincidentally targeting these obstacles would promote axonal regeneration. We combined (1) transplantation of a growth-permissive peripheral nerve graft (PNG) into an incomplete, cervical lesion cavity; (2) transduction of neurons rostral to the SCI site to express constitutively active Rheb (caRheb; a Ras homolog enriched in brain), a GTPase that directly activates the growth-promoting pathway mammalian target of rapamycin (mTOR) via AAV-caRheb injection; and (3) digestion of growth-inhibitory chondroitin sulfate proteoglycans within the glial scar at the distal PNG interface using the bacterial enzyme chondroitinase ABC (ChABC)...
August 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28945203/mtorc1-loss-impairs-epidermal-adhesion-via-tgf-%C3%AE-rho-kinase-activation
#9
Kaushal Asrani, Akshay Sood, Alba Torres, Dan Georgess, Pornima Phatak, Harsimar Kaur, Amber Dubin, C Conover Talbot, Loubna Elhelu, Andrew J Ewald, Bo Xiao, Paul Worley, Tamara L Lotan
Despite its central position in oncogenic intracellular signaling networks, the role of mTORC1 in epithelial development has not been studied extensively in vivo. Here, we have used the epidermis as a model system to elucidate the cellular effects and signaling feedback sequelae of mTORC1 loss of function in epithelial tissue. In mice with conditional epidermal loss of the mTORC1 components Rheb or Rptor, mTORC1 loss of function unexpectedly resulted in a profound skin barrier defect with epidermal abrasions, blistering, and early postnatal lethality, due to a thinned epidermis with decreased desmosomal protein expression and incomplete biochemical differentiation...
September 25, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28808055/dynamin-dependent-amino-acid-endocytosis-activates-mechanistic-target-of-rapamycin-complex-1-mtorc1
#10
Shusaku Shibutani, Hana Okazaki, Hiroyuki Iwata
The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of protein synthesis and potential target for modifying cellular metabolism in various conditions, including cancer and aging. mTORC1 activity is tightly regulated by the availability of extracellular amino acids, and previous studies have revealed that amino acids in the extracellular fluid are transported to the lysosomal lumen. There, amino acids induce recruitment of cytoplasmic mTORC1 to the lysosome by the Rag GTPases, followed by mTORC1 activation by the small GTPase Ras homolog enriched in brain (Rheb)...
November 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28768723/lamtor1-is-critically-required-for-cd4-t-cell-proliferation-and-regulatory-t-cell-suppressive-function
#11
Takashi Hosokawa, Tetsuya Kimura, Shigeyuki Nada, Tatsusada Okuno, Daisuke Ito, Sujin Kang, Satoshi Nojima, Kazuya Yamashita, Takeshi Nakatani, Yoshitomo Hayama, Yasuhiro Kato, Yuhei Kinehara, Masayuki Nishide, Norihisa Mikami, Syohei Koyama, Hyota Takamatsu, Daisuke Okuzaki, Naganari Ohkura, Shimon Sakaguchi, Masato Okada, Atsushi Kumanogoh
Mechanistic target of rapamycin complex (mTORC)1 integrates intracellular sufficiency of nutrients and regulates various cellular functions. Previous studies using mice with conditional knockout of mTORC1 component proteins (i.e., mTOR, Raptor, and Rheb) gave conflicting results on the roles of mTORC1 in CD4(+) T cells. Lamtor1 is the protein that is required for amino acid sensing and activation of mTORC1; however, the roles of Lamtor1 in T cells have not been investigated. In this article, we show that Lamtor1-deficient CD4(+) T cells exhibited marked reductions in proliferation, IL-2 production, mTORC1 activity, and expression of purine- and lipid-synthesis genes...
September 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28710231/tuberin-regulates-prostaglandin-receptor-mediated-viability-via-rheb-in-mtorc1-hyperactive-cells
#12
Chenggang Li, Xiaolei Liu, Yang Liu, Erik Zhang, Kantha Medepalli, Kouhei Masuda, Na Li, Kathryn A Wikenheiser-Brokamp, Andrew Osterburg, Michael T Borchers, Elizabeth J Kopras, David R Plas, Julia Sun, David N Franz, Jamie K Capal, Maxwell Mays, Yang Sun, David J Kwiatkowski, Anya Alayev, Marina K Holz, Darcy A Krueger, Brian J Siroky, Jane J Yu
Tuberous sclerosis complex (TSC) is a tumor-suppressor syndrome affecting multiple organs, including the brain, skin, kidneys, heart, and lungs. TSC is associated with mutations in TSC1 or TSC2, resulting in hyperactivation of mTOR complex 1 (mTORC1). Clinical trials demonstrate that mTORC1 inhibitors decrease tumor volume and stabilize lung function in TSC patients; however, mTOR inhibitors are cytostatic not cytocidal, and long-term benefits and toxicities are uncertain. Previously, we identified rapamycin-insensitive upregulation of cyclooxygenase 2 (PTGS2/COX2) and prostaglandin E2 (PGE2) production in TSC2-deficient cells and postulated that the action of excess PGE2 and its cognate receptors (EP) contributes to cell survival...
October 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28694500/resistance-exercise-initiates-mechanistic-target-of-rapamycin-mtor-translocation-and-protein-complex-co-localisation-in-human-skeletal-muscle
#13
Zhe Song, Daniel R Moore, Nathan Hodson, Carl Ward, Jessica R Dent, Mary F O'Leary, Andrew M Shaw, D Lee Hamilton, Sovan Sarkar, Yann-Gaël Gangloff, Troy A Hornberger, Lawrence L Spriet, George J Heigenhauser, Andrew Philp
The mechanistic target of rapamycin (mTOR) is a central mediator of protein synthesis in skeletal muscle. We utilized immunofluorescence approaches to study mTOR cellular distribution and protein-protein co-localisation in human skeletal muscle in the basal state as well as immediately, 1 and 3 h after an acute bout of resistance exercise in a fed (FED; 20 g Protein/40 g carbohydrate/1 g fat) or energy-free control (CON) state. mTOR and the lysosomal protein LAMP2 were highly co-localised in basal samples...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28658616/purine-nucleotide-availability-regulates-mtorc1-activity-through-the-rheb-gtpase
#14
Natasha Emmanuel, Shoba Ragunathan, Qin Shan, Fang Wang, Andreas Giannakou, Nanni Huser, Guixian Jin, Jeremy Myers, Robert T Abraham, Keziban Unsal-Kacmaz
Pharmacologic agents that interfere with nucleotide metabolism constitute an important class of anticancer agents. Recent studies have demonstrated that mTOR complex 1 (mTORC1) inhibitors suppress de novo biosynthesis of pyrimidine and purine nucleotides. Here, we demonstrate that mTORC1 itself is suppressed by drugs that reduce intracellular purine nucleotide pools. Cellular treatment with AG2037, an inhibitor of the purine biosynthetic enzyme GARFT, profoundly inhibits mTORC1 activity via a reduction in the level of GTP-bound Rheb, an obligate upstream activator of mTORC1, because of a reduction in intracellular guanine nucleotides...
June 27, 2017: Cell Reports
https://www.readbyqxmd.com/read/28647319/in-vitro-stimulation-of-vitellogenin-expression-by-insulin-in-the-mud-crab-scylla-paramamosain-mediated-through-pi3k-akt-tor-pathway
#15
Xiaoshuai Huang, Biyun Feng, Huiyang Huang, Haihui Ye
Vitellogenin (vtg) synthesis, known as vitellogenesis, is one of most important processes in the ovarian development of oviparous animals. Recently, multiple insulin-like peptides (ILPs) have been reported in crustacean species due to the application of transcriptome sequencing. In this context, the present study reports that the addition of an exogenous ILP, bovine insulin, stimulates vtg (termed Sp-vtg) expression in hepatopancreatic explants from the mud crab, Scylla paramamosain, by in vitro experiments...
June 21, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28641977/a-novel-fluorescent-probe-reveals-starvation-controls-the-commitment-of-amyloid-precursor-protein-to-the-lysosome
#16
Leanne K Hein, Pirjo M Apaja, Kathryn Hattersley, Randall H Grose, Jianling Xie, Christopher G Proud, Timothy J Sargeant
Alzheimer's disease is the most important cause of dementia but there is no therapy that has been demonstrated to stop or slow disease progression. Amyloid precursor protein (APP) is the source of amyloid-β (Aβ), which aggregates in Alzheimer's disease to form toxic oligomeric species. The endo-lysosomal system can clear APP and Aβ from the cell if these molecular species are trafficked through to the lysosome. Currently, there are no easy methods available for the analysis of lysosomal APP trafficking. We therefore generated a fusion protein (tandem-fluorescent, or tf-APP) that allows detection of changes in APP trafficking using accessible techniques such as flow cytometry...
October 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28638431/erzhi-pill%C3%A2-repairs-experimental-liver-injury-via-tsc-mtor-signaling-pathway-inhibiting-excessive-apoptosis
#17
Bu-Gao Zhou, Hai-Mei Zhao, Xiu-Yun Lu, Xin Wang, Yong Zou, Rong Xu, Hai-Yang Yue, Yi Liu, Zheng-Yun Zuo, Duan-Yong Liu
The present study aimed to investigate the mechanism of hepatoprotective effect of Erzhi Pill (EZP) on the liver injury via observing TSC/mTOR signaling pathway activation. The experimental liver injury was induced by 2-acetylaminofluorene (2-AAF) treatment combined with partial hepatectomy (PH). EZP treated 2-AAF/PH-induced liver injury by the therapeutic and prophylactic administration. After the administration of EZP, the activities of aspartic transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AKP), and gamma-glutamyl transpeptidase (γ-GT) were decreased, followed by the decreased levels of hepatocyte apoptosis and caspase-3 expression...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28625796/the-characterization-of-rheb-gene-and-its-responses-to-hypoxia-and-thermal-stresses-in-the-small-abalone-haliotis-diversicolor
#18
Lianghua He, Xin Zhang, Ying Huang, Huiping Yang, Yilei Wang, Ziping Zhang
RHEB (Ras Homolog Enriched in Brain) is a GTP-binding protein that is ubiquitously expressed in humans and other mammals. The protein is largely involved in the mechanistic target of rapamycin (mTOR) pathway, and regulates the cell cycle progression and growth. The goal of this study was to characterize the RHEB gene in the small abalone Haliotis diversicolor, and identify the responses of RHEB gene to stresses of hypoxia or/and thermal. The objectives were to: 1) clone the full-length cDNA RHEB gene in the H...
August 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28612328/antidepressant-actions-of-ketamine-mediated-by-the-mechanistic-target-of-rapamycin-nitric-oxide-and-rheb
#19
REVIEW
Maged M Harraz, Solomon H Snyder
The weeks/months it takes for traditional antidepressants to act pose an obstacle in the management of depression. Ketamine's prompt and sustained antidepressant effects constitute a major advance. Multiple studies implicate glutamatergic signaling to protein synthesis machinery and synapse formation in ketamine's antidepressant effects. Here we review evidence linking ketamine to glutamate receptor subtypes and protein homeostasis. We describe a signaling cascade wherein nitric oxide drives the formation of a ternary protein complex comprised of glyceraldehyde 3-phosphate dehydrogenase, seven in absentia homolog 1, and Ras homolog enriched in brain downstream of the glutamate N-methyl-D-aspartate receptor...
July 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28610953/a-thirty-year-quest-for-a-role-of-r-ras-in-cancer-from-an-oncogene-to-a-multitasking-gtpase
#20
REVIEW
Wai Nam Liu, Mingfei Yan, Andrew M Chan
Since the identification of R-Ras, which is the first Ras-related GTPase isolated based on sequence similarity to the classical RAS oncogene, more than 160 members of the Ras superfamily of GTPases have been identified and classified into the Ras, Rho, Rap, Rab, Ran, Arf, Rheb, RGK, Rad, Rit, and Miro subfamilies. R-Ras belongs to the Ras subfamily of small G-proteins, which are frequently implicated in cell growth and differentiation. Although the roles of R-Ras in cellular transformation and integrin-mediated cell adhesion have been extensively studied, the physiological function of this enigmatic G-protein was only revealed when a mouse strain deficient in R-Ras was generated...
September 10, 2017: Cancer Letters
keyword
keyword
44850
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"