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Ras protein

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https://www.readbyqxmd.com/read/28550141/role-of-dynamin-src-and-ras-in-the-protein-kinase-c-mediated-activation-of-erk-by-gonadotropin-releasing-hormone
#1
Outhiriaradjou Benard, Zvi Naor, Rony Seger
No abstract text is available yet for this article.
May 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28548933/kir2dl5-mutation-and-loss-underlies-sporadic-dermal-neurofibroma-pathogenesis-and-growth
#2
Corina Anastasaki, Sonika Dahiya, David H Gutmann
Dermal neurofibromas (DNFs) are benign peripheral nerve sheath tumors thought to originate from Schwann cell progenitors. These tumors represent one of the hallmarks of the neurofibromatosis type 1 (NF1) tumor predisposition syndrome, where they can number in the thousands. While NF1-DNFs arise due to mutations in the NF1 gene, the vast majority of DNFs occur sporadically (sp-DNFs), where the genetic etiology is currently unknown. Herein, we employed whole-exome sequencing of sp-DNFs to identify a recurrent mutation in the KIR2DL5 gene, which codes for a protein suppressor of natural killer (NK) cell activity...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28546426/guanine-nucleotide-exchange-factor-epac2-dependent-activation-of-the-gtp-binding-protein-rap2a-mediates-camp-dependent-growth-arrest-in-neuroendocrine-cells
#3
Andrew C Emery, Wenqin Xu, Maribeth V Eiden, Lee E Eiden
First messenger-dependent activation of MAPKs in neuronal and endocrine cells is critical for cell differentiation and function and requires guanine nucleotide exchange factor (GEF)- mediated activation of downstream Ras-family small GTPases, which ultimately lead to ERK, JNK, and p38 phosphorylation. Because there are numerous GEFs and also a host of Ras-family small GTPases, it is important to know which specific GEF-small GTPase dyad functions in a given cellular process. Here, we investigated the upstream activators and downstream effectors of signaling via the GEF Epac2 in the neuroendocrine NS-1 cell line...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28545687/synergistic-effect-of-mek-inhibitor-and-metformin-combination-in-low-grade-serous-ovarian-cancer
#4
Ismail Mert, Jasdeep Chhina, Ghassan Allo, Jing Dai, Shelly Seward, Mark S Carey, Marta Llaurado, Shailendra Giri, Ramandeep Rattan, Adnan R Munkarah
OBJECTIVE: Low-grade serous ovarian cancer (LGSOC) constitutes 5-8% of epithelial ovarian cancers and is refractory to chemotherapy. We and others have shown metformin to cause significant growth inhibition in high-grade ovarian cancer both in vitro and in vivo. Here, we aimed to analyze if metformin was effective in inhibiting proliferation of LGSOC alone and in combination with MEK inhibitor. METHODS: Three LGSOC lines (VOA1056, VOA1312 and VOA5646) were treated with metformin, trametinib or 2-deoxyglucose (2DG) alone or in combination with metformin...
May 22, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28542501/a-rho-associated-coiled-coil-containing-kinases-rock-inhibitor-y-27632-enhances-adhesion-viability-and-differentiation-of-human-term-placenta-derived-trophoblasts-in-vitro
#5
Kenichiro Motomura, Naoko Okada, Hideaki Morita, Mariko Hara, Masato Tamari, Keisuke Orimo, Go Matsuda, Ken-Ichi Imadome, Akio Matsuda, Takeshi Nagamatsu, Mikiya Fujieda, Haruhiko Sago, Hirohisa Saito, Kenji Matsumoto
Although human term placenta-derived primary cytotrophoblasts (pCTBs) represent a good human syncytiotrophoblast (STB) model, in vitro culture of pCTBs is not always easily accomplished. Y-27632, a specific inhibitor of Rho-associated coiled-coil containing kinases (ROCK), reportedly prevented apoptosis and improved cell-to-substrate adhesion and culture stability of dissociated cultured human embryonic stem cells and human corneal endothelial cells. The Rho kinase pathway regulates various kinds of cell behavior, some of which are involved in pCTB adhesion and differentiation...
2017: PloS One
https://www.readbyqxmd.com/read/28540724/pde%C3%AE-binding-to-ras-isoforms-provides-a-route-to-proper-membrane-localization
#6
Serena Muratcioglu, Hyunbum Jang, Attila Gursoy, Ozlem Keskin, Ruth Nussinov
To signal, Ras isoforms must be enriched at the plasma membrane (PM). It was suggested that phosphodiesterase-δ (PDEδ) can bind and shuttle some farnesylated Ras isoforms to the PM - but not all. Among these, interest focused on K-Ras4B, the most abundant oncogenic Ras isoform. To study PDEδ/Ras interactions, we modeled and simulated the PDEδ/K-Ras4B complex. We obtained structures which were similar to two subsequently determined crystal structures. We next modeled and simulated complexes of PDEδ with the farnesylated hypervariable regions (HVRs) of K-Ras4A and N-Ras...
May 25, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28538729/cryo-em-structure-of-the-activated-glp-1-receptor-in-complex-with-a-g-protein
#7
Yan Zhang, Bingfa Sun, Dan Feng, Hongli Hu, Matthew Chu, Qianhui Qu, Jeffrey T Tarrasch, Shane Li, Tong Sun Kobilka, Brian K Kobilka, Georgios Skiniotis
Glucagon-like peptide 1 (GLP-1) is a hormone with essential roles in regulating insulin secretion, carbohydrate metabolism and appetite. GLP-1 effects are mediated through binding to the GLP-1 receptor (GLP-1R), a class B G-protein-coupled receptor (GPCR) that signals primarily through the stimulatory G protein Gs. Class B GPCRs are important therapeutic targets; however, our understanding of their mechanism of action is limited by the lack of structural information on activated and full-length receptors. Here we report the cryo-electron microscopy structure of the peptide-activated GLP-1R-Gs complex at near atomic resolution...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28538214/profiling-and-bioinformatic-analysis-of-circular-rna-expression-regulated-by-c-myc
#8
Qiheng Gou, Ke Wu, Jian-Kang Zhou, Yuxin Xie, Lunxu Liu, Yong Peng
The c-Myc transcription factor is involved in cell proliferation, cell cycle and apoptosis by activating or repressing transcription of multiple genes. Circular RNAs (circRNAs) are widely expressed non-coding RNAs participating in the regulation of gene expression. Using a high-throughput microarray assay, we showed that Myc regulates the expression of certain circRNAs. A total of 309 up- and 252 down-regulated circRNAs were identified. Among them, randomly selected 8 circRNAs were confirmed by real-time PCR...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536481/trpv4-dependent-induction-of-a-novel-mammalian-cold-inducible-protein-srsf5-as-well-as-cirp-and-rbm3
#9
Takanori Fujita, Hiroaki Higashitsuji, Hisako Higashitsuji, Yu Liu, Katsuhiko Itoh, Toshiharu Sakurai, Takahiro Kojima, Shuya Kandori, Hiroyuki Nishiyama, Motoi Fukumoto, Manabu Fukumoto, Koji Shibasaki, Jun Fujita
Cold-inducible RNA-binding protein (CIRP) and RNA-binding motif protein 3 (RBM3) are two evolutionarily conserved RNA-binding proteins that are structurally related to hnRNPs and upregulated in response to moderately low temperatures in mammalian cells. Although contributions of splicing efficiency, the gene promoters activated upon mild hypothermia and the transcription factor Sp1 to induction of CIRP have been reported, precise mechanisms by which hypothermia and other stresses induce the expression of mammalian cold-inducible proteins (CIPs) are poorly understood...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536037/identification-of-molecular-targets-in-vulvar-cancers
#10
Marguerite L Palisoul, Mary M Mullen, Rebecca Feldman, Premal H Thaker
OBJECTIVES: To identify molecular alterations that contribute to vulvar cancer pathogenesis with the intent of identifying molecular targets for treatment. METHODS: After retrospective analysis of a database of molecularly-profiled gynecologic cancer patients, 149 vulvar cancer patients were included and tested centrally at a CLIA laboratory (Caris Life Sciences, Phoenix, AZ). Tests included one or more of the following: gene sequencing (Sanger or next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]), and gene amplification (C/FISH)...
May 20, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28535453/inhibition-of-neddylation-modification-sensitizes-pancreatic-cancer-cells-to-gemcitabine
#11
Hua Li, Weihua Zhou, Lihui Li, Jianfu Wu, Xiaoli Liu, Lili Zhao, Lijun Jia, Yi Sun
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA with a 5-year survival rate less than 3% to 5%. Gemcitabine remains as a standard care for PDAC patients. Although protein neddylation is abnormally activated in many human cancers, whether neddylation dysregulation is involved in PDAC and whether targeting neddylation would sensitize pancreatic cancer cells to gemcitabine remain elusive. Here we report that high expression of neddylation components, NEDD8 and NAE1, are associated with poor survival of PDAC patients...
May 20, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28535374/discovery-of-stromal-regulatory-networks-that-suppress-ras-sensitized-epithelial-cell-proliferation
#12
Huayang Liu, James A Dowdle, Safiya Khurshid, Nicholas J Sullivan, Nicholas Bertos, Komal Rambani, Markus Mair, Piotr Daniel, Esther Wheeler, Xing Tang, Kyle Toth, Michael Lause, Markus E Harrigan, Karl Eiring, Connor Sullivan, Matthew J Sullivan, Serena W Chang, Siddhant Srivastava, Joseph S Conway, Raleigh Kladney, Joseph McElroy, Sooin Bae, Yuanzhi Lu, Ali Tofigh, Sadiq M I Saleh, Soledad A Fernandez, Jeffrey D Parvin, Vincenzo Coppola, Erin R Macrae, Sarmila Majumder, Charles L Shapiro, Lisa D Yee, Bhuvaneswari Ramaswamy, Michael Hallett, Michael C Ostrowski, Morag Park, Helen M Chamberlin, Gustavo Leone
Mesodermal cells signal to neighboring epithelial cells to modulate their proliferation in both normal and disease states. We adapted a Caenorhabditis elegans organogenesis model to enable a genome-wide mesodermal-specific RNAi screen and discovered 39 factors in mesodermal cells that suppress the proliferation of adjacent Ras pathway-sensitized epithelial cells. These candidates encode components of protein complexes and signaling pathways that converge on the control of chromatin dynamics, cytoplasmic polyadenylation, and translation...
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28534935/effect-of-fasudil-on-cognitive-function-following-status-convulsion-in-rats
#13
Rong He, Wei Han, Xiaojie Song, Xiaoju Tang, Li Cheng, Li Jiang
Fasudil has been demonstrated to possess a protective effect in neural injury; however, its protective effect on convulsive brain injury remains to be assessed. The aim of the present study was to investigate the latent mechanism and effect of fasudil on cognitive function following status convulsion (SC) in rats. Initially, to determine the effects of SC, the expression levels of Ras homolog gene family, member A (RhoA)/Rho‑associated protein kinase (ROCK) signaling pathway‑associated proteins were measured by western blot analysis in 16 rats...
May 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28532817/-pro-renin-receptor-as-a-therapeutic-target-for-the-treatment-of-cardiovascular-diseases
#14
REVIEW
Yuan Sun, A H Jan Danser, Xifeng Lu
The discovery of the (pro)renin receptor [(P)RR] 15years ago stimulated ideas on prorenin being more than renin's inactive precursor. Indeed, binding of prorenin to the (P)RR induces a conformational change in the prorenin molecule, allowing it to display angiotensin-generating activity, and additionally results in intracellular signaling in an angiotensin-independent manner. However, the prorenin levels required to observe these angiotensin-dependent and -independent effects of the (P)RR are many orders above its in vivo concentrations, both under normal and pathological conditions...
May 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28531801/ace-2-ang1-7-mas-cascade-mediates-ace-inhibitor-captopril-protective-effects-in-estrogen-deficient-osteoporotic-rats
#15
Hatem M Abuohashish, Mohammed M Ahmed, Dina Sabry, Mahmoud M Khattab, Salim S Al-Rejaie
The local role of the renin angiotensin system (RAS) was documented recently beside its conventional systemic functions. Studies showed that the effector angiotensin II (AngII) alters bone health, while inhibition of the angiotensin converting enzyme (ACE-1) preserved these effects. The newly identified Ang1-7 exerts numerous beneficial effects opposing the AngII. Thus, the current study examines the role of Ang1-7 in mediating the osteo-preservative effects of ACEI (captopril) through the G-protein coupled Mas receptor using an ovariectomized (OVX) rat model of osteoporosis...
May 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28530642/rasa1-regulates-the-function-of-lymphatic-vessel-valves-in-mice
#16
Philip E Lapinski, Beth A Lubeck, Di Chen, Abbas Doosti, Scott D Zawieja, Michael J Davis, Philip D King
Capillary malformation-arteriovenous malformation (CM-AVM) is a blood and lymphatic vessel (LV) disorder that is caused by inherited inactivating mutations of the RASA1 gene, which encodes p120 RasGAP (RASA1), a negative regulator of the Ras small GTP-binding protein. How RASA1 mutations lead to the LV leakage defects that occur in CM-AVM is not understood. Here, we report that disruption of the Rasa1 gene in adult mice resulted in loss of LV endothelial cells (LECs) specifically from the leaflets of intraluminal valves in collecting LVs...
May 22, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28529064/analysis-of-post-transcriptional-regulation-during-cancer-progression-using-a-donor-derived-isogenic-model-of-tumorigenesis
#17
Laura S Bisogno, Jack D Keene
Post-transcriptional regulation of gene expression by RNA binding proteins (RBPs) and non-coding RNAs plays an important role in global gene expression. Many post-transcriptional regulators are misexpressed and misregulated in cancers, resulting in altered programs of protein biosynthesis that can drive tumor progression. While comparative studies of several RBPs and microRNAs expressed in various cancer types have been reported, a model system that can be used to quantify RBP regulation and functional outcomes during the initiation and early stages of tumorigenesis is lacking...
May 18, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28526854/induction-of-senescence-in-primary-glioblastoma-cells-by-serum-and-tgf%C3%AE
#18
Ritesh Kumar, Alexander Gont, Theodore J Perkins, Jennifer E L Hanson, Ian A J Lorimer
Glioblastoma is the most common type of adult brain tumour and has a median survival after diagnosis of a little more than a year. Glioblastomas have a high frequency of mutations in the TERT promoter and CDKN2A locus that are expected to render them resistant to both replicative and oncogene-induced senescence. However, exposure of PriGO8A primary glioblastoma cells to media with 10% serum induced a senescence-like phenotype characterized by increased senescence-associated β galactosidase activity, PML bodies and p21 and morphological changes typical of senescence...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526321/effects-of-dehp-and-its-metabolite-mehp-on-insulin-signalling-and-proteins-involved-in-glut4-translocation-in-cultured-l6-myotubes
#19
Mangala Priya Viswanathan, Vigneswari Mullainadhan, Mayilvanan Chinnaiyan, Balasubramanian Karundevi
Di-(2-ethylhexyl)phthalate (DEHP) is the plasticizer used in variety of medical and consumer products to impart structural flexibility. DEHP and its primary metabolite mono-(2-ethyl hexyl)phthalate (MEHP) posed a considerable interest because of their contribution to insulin resistance, type-2 diabetes and obesity. Experimental and epidemiological data have shown that DEHP affects blood glucose homeostasis. However, direct effect of DEHP and its metabolite MEHP on insulin signal transduction and glucose transporter 4 (GLUT4) translocation remain obscure...
May 16, 2017: Toxicology
https://www.readbyqxmd.com/read/28525902/mir-148a-impairs-ras-erk-signaling-in-b-lymphocytes-by-targeting-sos-proteins
#20
Julia Alles, Nicole Ludwig, Stefanie Rheinheimer, Petra Leidinger, Friedrich A Grässer, Andreas Keller, Eckart Meese
Although microRNAs have been recognized as central cellular regulators, there is an evident lack of knowledge about their targets. Here, we analyzed potential target genes for miR-148a functioning in Ras signaling in B cells, including SOS1 and SOS2. A dual-luciferase reporter assay showed significantly decreased luciferase activity upon ectopic overexpression of miR-148a in HEK-293T cells that were co-transfected with the 3'UTR of either SOS1 or SOS2. Each of the 3'UTRs of SOS1 and SOS2 contained two binding sites for miR-148a both of which were necessary for the decreased luciferase activity...
May 7, 2017: Oncotarget
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