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Rho GTPases

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https://www.readbyqxmd.com/read/28729673/distinct-functional-relevance-of-dynamic-gtpase-cysteine-methylation-in-fission-yeast
#1
Alejandro Franco, Teresa Soto, Rebeca Martín-García, Marisa Madrid, Beatriz Vázquez-Marín, Jero Vicente-Soler, Pedro M Coll, Mariano Gacto, Pilar Pérez, José Cansado
The final step in post-translational processing of Ras and Rho GTPases involves methylation of the prenylated cysteine residue by an isoprenylcysteine-O-carboxyl methyltransferase (ICMT). ICMT activity is essential for cell growth and development in higher eukaryotes, and inhibition of GTPase methylation has become an attractive target in cancer therapy to inactivate prenylated oncoproteins. However, the specificity and dynamics of the GTPase methylation process remain to be fully clarified. Notably, cells lacking Mam4, the ICMT ortholog in the fission yeast Schizosaccharomyces pombe, are viable...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724429/the-noncoding-rna-hoxd-as1-is-a-critical-regulator-of-the-metastasis-and-apoptosis-phenotype-in-human-hepatocellular-carcinoma
#2
Shan Lu, Jiansheng Zhou, Yimin Sun, Nan Li, Mingyong Miao, Binghua Jiao, Huan Chen
BACKGROUND: Despite accumulating evidence that long noncoding RNAs (lncRNAs) are associated with cancer development in multiple types of cancer, the biological roles of many lncRNAs in human hepatocellular carcinoma (HCC) metastasis have not been well characterized. METHODS: A lncRNA+ mRNA human gene expression microarray analysis was used to identify differentially expressed lncRNAs in metastatic HCC tissues compared to non-metastatic tissue. RESULTS: We observed remarkable overexpression of HOXD-AS1 in metastatic cancer tissues...
July 19, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28720584/protein-kinase-n2-regulates-amp-kinase-signaling-and-insulin-responsiveness-of-glucose-metabolism-in-skeletal-muscle
#3
Maxwell A Ruby, Isabelle Riedl, Julie Massart, Marcus Åhlin, Juleen R Zierath
Insulin resistance is central to the development of type 2 diabetes and related metabolic disorders. As skeletal muscle is responsible for the majority of whole body insulin-stimulated glucose uptake, regulation of glucose metabolism in this tissue is of particular importance. While Rho GTPases and many of their affecters influence skeletal muscle metabolism, there is a paucity of information on the protein kinase N (PKN) family of serine/threonine protein kinases. We investigated the impact of PKN2 on insulin signaling and glucose metabolism in primary human skeletal muscle cells in vitro and mouse tibialis anterior muscle in vivo...
July 18, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28712859/tyr42-phosphorylation-of-rhoa-gtpase-promotes-tumorigenesis-through-nuclear-factor-nf-%C3%AE%C2%BAb
#4
Jae-Gyu Kim, Kyoung-Chan Choi, Chang-Won Hong, Hwee-Seon Park, Eun-Kyoung Choi, Yong-Sun Kim, Jae-Bong Park
Dysregulation of reactive oxygen species (ROS) levels is implicated in the pathogenesis of several diseases, including cancer. However, the molecular mechanisms of ROS in tumorigenesis have not been clearly elucidated. Hydrogen peroxide activated nuclear factor-κB (NF-κB) and RhoA GTPase. In particular, we found that hydrogen peroxide phosphorylated RhoA at Tyr42 via Src. P-Ty42 residue of RhoA was a binding site of Vav2, a guanine nucleotide exchange factor (GEF) that activates p-Tyr42 RhoA. P-Tyr42 RhoA then bound to IκB kinase γ (IKKγ), leading IKKβ activation...
July 13, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28710770/an-arabidopsis-kinase-cascade-influences-auxin-responsive-cell-expansion
#5
Tara A Enders, Elizabeth M Frick, Lucia C Strader
Mitogen-activated protein kinase (MPK) cascades are conserved mechanisms of signal transduction across eukaryotes. Despite the importance of MPK proteins in signaling events, specific roles for many Arabidopsis MPK proteins remain unknown. Multiple studies have suggested roles for MPK signaling in a variety of auxin-related processes. To identify MPK proteins with roles in auxin response, we screened mpk insertional alleles and identified mpk1-1 as a mutant that displays hypersensitivity in auxin-responsive cell expansion assays...
July 15, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28709956/activation-of-human-gonadotropin-releasing-hormone-receptor-promotes-down-regulation-of-arhgap18-and-regulates-the-cell-invasion-of-mda-mb-231%C3%A2-cells
#6
Arturo Aguilar-Rojas, Guadalupe Maya-Núñez, Maira Huerta-Reyes, Marco Allán Pérez-Solis, Raúl Silva-García, Nancy Guillén, Jean-Christophe Olivo-Marin
The Gonadotropin-Releasing Hormone Receptor (GnRHR) is expressed mainly in the gonadotrope membrane of the adenohypophysis and its natural ligand, the Gonadotropin-Releasing Hormone (GnRH), is produced in anterior hypothalamus. Furthermore, both molecules are also present in the membrane of cells derived from other reproductive tissues such as the breast, endometrium, ovary, and prostate, as well as in tumors derived from these tissues. The functions of GnRH receptor and its hormone in malignant cells have been related with the decrease of proliferation and the invasiveness of those tumors however, little is known about the molecules associated with the signaling pathways regulated by both molecules in malignant cells...
July 11, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28709595/losing-their-footing-rac1-signaling-causes-podocyte-detachment-and-fsgs
#7
Gentzon Hall, Robert F Spurney
Selective modulation of Rho GTPase activity in podocytes recapitulates characteristic features of human nephrosis. Using a mouse model, Robins et al. found that high levels of Rac1 activation in podocytes caused podocyte detachment and glomerulosclerosis. Podocyte Rac1 activity was enhanced in biopsy specimens from patients with nephrosis, and serum from this patient population activated Rac1 in cultured podocytes. These data provide a causal link between podocyte Rac1 activation and human nephrotic diseases...
August 2017: Kidney International
https://www.readbyqxmd.com/read/28709063/regulation-of-rho-gtpase-proteins-during-spine-structural-plasticity-for-the-control-of-local-dendritic-plasticity
#8
REVIEW
Nathan G Hedrick, Ryohei Yasuda
While it is generally appreciated that learning involves the structural rearrangement of neuronal circuits, the underlying orchestration of molecular events that drives these changes is not as well understood. Recent studies on the spatiotemporal organization of synaptic signaling events have provided new insights into the biochemical underpinnings of various expressions of structural neuronal plasticity, as well as the functional consequences that emerge because of the particular behavior of the molecules involved...
July 11, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28704809/istaroxime-inhibits-motility-and-down-regulates-orai1-expression-soce-and-fak-phosphorylation-in-prostate-cancer-cells
#9
Matias Julian Stagno, Nefeli Zacharopoulou, Jonas Bochem, Anna Tsapara, Lisann Pelzl, Tamer Al-Maghout, Galatea Kallergi, Saad Alkahtani, Konstantinos Alevizopoulos, Konstantinos Dimas, Theodora Calogeropoulou, Steven W Warmann, Florian Lang, Evi Schmid, Christos Stournaras
BACKGROUND/AIMS: Istaroxime is a validated inotropic Na+/K+ ATPase inhibitor currently in development for the treatment of various cardiac conditions. Recent findings established that this steroidal drug exhibits potent apoptotic responses in prostate tumors in vitro and in vivo, by affecting key signaling orchestrating proliferation and apoptosis, such as c-Myc and caspase 3, Rho GTPases and actin cytoskeleton dynamics. In the present study we examined whether istaroxime is affecting cell motility and analyzed the underlying mechanism in prostate tumor cells...
July 14, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28701658/drosophila-dock-family-protein-zizimin-involves-in-pigment-cell-differentiation-in-pupal-retinae
#10
Fumito Ozasa, Kazushige Morishita, Ngoc Anh Suong Dang, Seiji Miyata, Hideki Yoshida, Masamitsu Yamaguchi
The dedicator of cytokinesis (DOCK) family proteins are known as one of guanine nucleotide exchange factors (GEFs), that contribute to cellular signaling processes by activating small G proteins. Although mammalian Zizimin is known to be a GEF for Cdc42 of Rho family small GTPase, its role in vivo is not well understood. Here we studied in vivo function of Drosophila Zizimin (Ziz). Knockdown of Ziz in eye imaginal discs induced the rough eye phenotype accompanied with fusion of ommatidia, loss of bristles and loss of pigments...
July 13, 2017: Cell Structure and Function
https://www.readbyqxmd.com/read/28699510/cell-penetrating-peptides-a-promising-tool-for-the-cellular-uptake-of-macromolecular-drugs
#11
Peipei Zhu, Lan Jin
The lipid bilayer of the plasma membrane is a selective impermeable barrier for the internalization of most macromolecules. Cell penetrating peptides (CPPs) could cross the plasma membrane barrier to deliver various molecules into cells and are considered as a promising tool to deliver macromolecular drugs. However, the exact cellular uptake mechanisms of CPPs are still ambiguous. It was reported that the exact cellular uptake pathway was determined by numerous factors such as the amino acid sequences (hydrophobicity and net charge), extracellular CPP concentration, cargoes' properties, cell type and the temperature...
July 10, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28698357/ropgef1-plays-a-critical-role-in-polar-auxin-transport-in-early-development
#12
Yuting Liu, Qingkun Dong, Daniel Kita, Jia-Bao Huang, Guolan Liu, Xiaowei Wu, Xiaoyue Zhu, Alice Y Cheung, Hen-Ming Wu, Li-Zhen Tao
Polar auxin transport, facilitated by the combined activities of auxin influx and efflux carriers to maintain asymmetric auxin distribution, is essential for plant growth and development. Here, we show that Arabidopsis RopGEF1, a guanine nucleotide exchange factor and activator of ROPs (Rho GTPases of plants), is critically involved in polar distribution of auxin influx carrier AUX1 and differential accumulation of efflux carriers PIN7 and PIN2, and is important for embryo and early seedling development when RopGEF1 is prevalently expressed...
July 11, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28697804/ang-ii-at2r-increases-mesenchymal-stem-cell-migration-by-signaling-through-the-fak-and-rhoa-cdc42-pathways-in-vitro
#13
Xiu-Ping Xu, Hong-Li He, Shu-Ling Hu, Ji-Bin Han, Li-Li Huang, Jing-Yuan Xu, Jian-Feng Xie, Ai-Ran Liu, Yi Yang, Hai-Bo Qiu
BACKGROUND: Mesenchymal stem cells (MSCs) migrate via the bloodstream to sites of injury and are possibly attracted by inflammatory factors. As a proinflammatory mediator, angiotensin II (Ang II) reportedly enhances the migration of various cell types by signaling via the Ang II receptor in vitro. However, few studies have focused on the effects of Ang II on MSC migration and the underlying mechanisms. METHODS: Human bone marrow MSCs migration was measured using wound healing and Boyden chamber migration assays after treatments with different concentrations of Ang II, an AT1R antagonist (Losartan), and/or an AT2R antagonist (PD-123319)...
July 12, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28696829/unraveling-a-model-of-tcl-rhoj-allosterism-using-tc10-reverse-chimeras
#14
Rebecca R Florke, Grace T Young, Michael J Hamann
In addition to the classical regulation of GTPase activity by effector proteins, investigating the variations in the amino acid sequence and structures of GTPases often provides insights into regulatory mechanisms that are more GTPase-specific. TCL/RhoJ is a Rho GTPase most closely related to Cdc42 and TC10; however, its nucleotide exchange activity is distinctly influenced by N-terminal amino acids 17-20 and the more distal amino acids 121-129. In this short study, we have further explored the differences between TCL and its homologue TC10 and show that its unique mode of allosteric regulation requires broader diversification of its amino acid sequence than previously appreciated...
July 11, 2017: Small GTPases
https://www.readbyqxmd.com/read/28691928/mutations-in-5-methylcytosine-oxidase-tet2-and-rhoa-cooperatively-disrupt-t-cell-homeostasis
#15
Shengbing Zang, Jia Li, Haiyan Yang, Hongxiang Zeng, Wei Han, Jixiang Zhang, Minjung Lee, Margie Moczygemba, Sevinj Isgandarova, Yaling Yang, Yubin Zhou, Anjana Rao, M James You, Deqiang Sun, Yun Huang
Angioimmunoblastic T cell lymphoma (AITL) represents a distinct, aggressive form of peripheral T cell lymphoma with a dismal prognosis. Recent exome sequencing in patients with AITL has revealed the frequent coexistence of somatic mutations in the Rho GTPase RhoA (RhoAG17V) and loss-of-function mutations in the 5-methylcytosine oxidase TET2. Here, we have demonstrated that TET2 loss and RhoAG17V expression in mature murine T cells cooperatively cause abnormal CD4+ T cell proliferation and differentiation by perturbing FoxO1 gene expression, phosphorylation, and subcellular localization, an abnormality that is also detected in human primary AITL tumor samples...
July 10, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28689384/cross-talk-between-src-kinases-and-rho-small-gtpases-regulates-biomineralization-and-simplify-imaging-of-the-mineralization-process
#16
Agnieszka Strzelecka-Kiliszek, Łukasz Bożycki
The process of physiological mineralization that occurs during bone ossification is a tightly regulated cascade of molecular events leading to formation of bony skeleton. Its deregulation associated with aging leads to pathological mineralization not only in osseous but also in soft tissues. Recent discoveries in the field of bone biology indicate the participation of the Src family of tyrosine kinases as well as the Rho family of small GTPases in mineral formation. Cross-talk between these two signaling pathways is activated during an early step of the mineralization process, and leads to reorganization of the cytoskeleton of mineralization-competent cells and to matrix vesicles release...
2017: Postepy Biochemii
https://www.readbyqxmd.com/read/28688003/increased-training-intensity-induces-proper-membrane-localization-of-actin-remodeling-proteins-in-the-hippocampus-preventing-cognitive-deficits-implications-for-fragile-x-syndrome
#17
L A Martinez, Maria Victoria Tejada-Simon
Behavioral intervention therapy has proven beneficial in the treatment of autism and intellectual disabilities (ID), raising the possibility of certain changes in molecular mechanisms activated by these interventions that may promote learning. Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by autistic features and intellectual disability and can serve as a model to examine mechanisms that promote learning. FXS results from mutations in the fragile X mental retardation 1 gene (Fmr1) that prevents expression of the Fmr1 protein (FMRP), a messenger RNA (mRNA) translation regulator at synapses...
July 8, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28684793/differentiating-staphylococcus-aureus-from-escherichia-coli-mastitis-s-aureus-triggers-unbalanced-immune-dampening-and-host-cell-invasion-immediately-after-udder-infection
#18
Juliane Günther, Wolfram Petzl, Isabel Bauer, Siriluck Ponsuksili, Holm Zerbe, Hans-Joachim Schuberth, Ronald M Brunner, Hans-Martin Seyfert
The etiology determines quality and extent of the immune response after udder infection (mastitis). Infections with Gram negative bacteria (e.g. Escherichia coli) will quickly elicit strong inflammation of the udder, fully activate its immune defence via pathogen receptor driven activation of IκB/NF-κB signaling. This often eradicates the pathogen. In contrast, Gram-positive bacteria (e.g. Staphylococcus aureus) will slowly elicit a much weaker inflammation and immune response, frequently resulting in chronic infections...
July 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28683469/lurbinectedin-reduces-tumour-associated-macrophages-and-the-inflammatory-tumour-microenvironment-in-preclinical-models
#19
Cristina Belgiovine, Ezia Bello, Manuela Liguori, Ilaria Craparotta, Laura Mannarino, Lara Paracchini, Luca Beltrame, Sergio Marchini, Carlos M Galmarini, Alberto Mantovani, Roberta Frapolli, Paola Allavena, Maurizio D'Incalci
BACKGROUND: Lurbinectedin is a novel anticancer agent currently undergoing late-stage (Phase II /III) clinical evaluation in platinum-resistant ovarian, BRCA1/2-mutated breast and small-cell lung cancer. Lurbinectedin is structurally related to trabectedin and it inhibits active transcription and the DNA repair machinery in tumour cells. METHODS: In this study we investigated whether lurbinectedin has the ability to modulate the inflammatory microenvironment and the viability of myeloid cells in tumour-bearing mice...
July 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28679606/proteomic-profile-of-cystic-fibrosis-sputum-cells-in-adults-chronically-infected-with-pseudomonas-aeruginosa
#20
Sally H Pattison, David S Gibson, Elinor Johnston, Samantha Peacock, Keith Rivera, Michael M Tunney, Darryl J Pappin, J Stuart Elborn
Lung disease is the main cause of morbidity and mortality in cystic fibrosis (CF), and involves chronic infection and perturbed immune responses. Tissue damage is mediated mostly by extracellular proteases, but other cellular proteins may also contribute to damage through their effect on cell activities and/or release into sputum fluid by means of active secretion or cell death.We employed MudPIT (multidimensional protein identification technology) to identify sputum cellular proteins with consistently altered abundance in adults with CF, chronically infected with Pseudomonas aeruginosa, compared with healthy controls...
July 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
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