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Rac1 RhoA

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https://www.readbyqxmd.com/read/29055784/rac1-modulates-g-protein-coupled-receptor-induced-bronchial-smooth-muscle-contraction
#1
Hiroyasu Sakai, Yuki Kai, Ken Sato, Mitsuo Ikebe, Yohihiko Chiba
Increasing evidence suggests a functional role of RhoA/Rho-kinase signalling as a mechanism for smooth muscle contraction; however, little is known regarding the roles of Rac1 and other members of the Rho protein family. This study aimed to examine whether Rac1 modulates bronchial smooth muscle contraction. Ring preparations of bronchi isolated from rats were suspended in an organ bath, and isometric contraction of circular smooth muscle was measured. Immunoblotting was used to examine myosin light chain phosphorylation in bronchial smooth muscle...
October 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29050986/rac1-plays-a-role-in-cxcl12-but-not-ccl3-induced-chemotaxis-and-rac1-gef-inhibitor-nsc23766-has-off-target-effects-on-cxcr4
#2
Shirley C Mills, Lesley Howell, Andrew Beekman, Leanne Stokes, Anja Mueller
Cell migration towards a chemotactic stimulus relies on the re-arrangement of the cytoskeleton, which is triggered by activation of small G proteins RhoA, Rac1 and Cdc42, and leads to formation of lamellopodia and actin polymerisation amongst other effects. Here we show that Rac1 is important for CXCR4 induced chemotaxis but not for CCR1/CCR5 induced chemotaxis. For CXCL12-induced migration via CXCR4, breast cancer MCF-7 cells are reliant on Rac1, similarly to THP-1 monocytes and Jurkat T-cells. For CCL3-induced migration via CCR1 and/or CCR5, Rac1 signalling does not regulate cell migration in either suspension or adherent cells...
October 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29043078/a-gap-that-divides
#3
REVIEW
Angika Basant, Michael Glotzer
Cytokinesis in metazoan cells is mediated by an actomyosin-based contractile ring that assembles in response to activation of the small GTPase RhoA. The guanine nucleotide exchange factor that activates RhoA during cytokinesis, ECT-2, is highly regulated. In most metazoan cells, with the notable exception of the early Caenorhabditis elegans embryo, RhoA activation and furrow ingression require the centralspindlin complex. This exception is due to the existence of a parallel pathway for RhoA activation in C...
2017: F1000Research
https://www.readbyqxmd.com/read/29042792/low-dose-of-kaempferol-suppresses-the-migration-and-invasion-of-triple-negative-breast-cancer-cells-by-downregulating-the-activities-of-rhoa-and-rac1
#4
Shoushan Li, Ting Yan, Rong Deng, Xuesong Jiang, Huaping Xiong, Yuan Wang, Qiao Yu, Xiaohua Wang, Cheng Chen, Yichao Zhu
PURPOSE: Triple-negative breast cancer (TNBC) is an especially aggressive and hard-to-treat disease. Although the anticancer role of kaempferol has been reported in breast cancer, the effect of kaempferol on TNBC remains unclear. MATERIALS AND METHODS: This experiment investigated the migration-suppressive role of a low dose of kaempferol in TNBC cells. Wound-healing assays and cell invasion assays were used to confirm the migration and invasion of cells treated with kaempferol or transfected indicated constructs...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29039527/simvastatin-inhibits-the-expression-of-stemness%C3%A2-related-genes-and-the-metastatic-invasion-of-human-cancer-cells-via-destruction-of-the-cytoskeleton
#5
Rosarita Tatè, Enrica Zona, Rosanna De Cicco, Veronica Trotta, Maria Urciuoli, Alessandro Morelli, Salvatore Baiano, Rosa Carnuccio, Maria Pia Fuggetta, Franco Morelli
Statins are a class of drugs that inhibit the rate-limiting steps in the cholesterol biosynthesis pathway. They act by inhibiting 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate. Blocking of mevalonate synthesis leads to inhibition of the farnesylation and geranylgeranylation of several functional proteins, such as RhoA and other small guanosine triphosphate-binding proteins, that are important in maintaining the undifferentiated status of the cells...
October 13, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29036929/interaction-between-rho-gtpases-and-14-3-3-proteins
#6
REVIEW
Daniel Brandwein, Zhixiang Wang
The Rho GTPase family accounts for as many as 20 members. Among them, the archetypes RhoA, Rac1, and Cdc42 have been the most well-characterized. Like all members of the small GTPases superfamily, Rho proteins act as molecular switches to control cellular processes by cycling between active, GTP-bound and inactive, GDP-bound states. The 14-3-3 family proteins comprise seven isoforms. They exist as dimers (homo- or hetero-dimer) in cells. They function by binding to Ser/Thr phosphorylated intracellular proteins, which alters the conformation, activity, and subcellular localization of their binding partners...
October 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29016860/primary-angle-closure-glaucoma-pacg-susceptibility-gene-plekha7-encodes-a-novel-rac1-cdc42-gap-that-modulates-cell-migration-and-blood-aqueous-barrier-function
#7
Mei-Chin Lee, William Shei, Anita S Chan, Boon-Tin Chua, Shuang-Ru Goh, Yaan-Fun Chong, Maryam H Hilmy, Monisha E Nongpiur, Mani Baskaran, Chiea-Chuen Khor, Tin Aung, Walter Hunziker, Eranga N Vithana
PLEKHA7, a gene recently associated with primary angle closure glaucoma (PACG), encodes an apical junctional protein expressed in components of the blood aqueous barrier (BAB). We found that PLEKHA7 is down-regulated in lens epithelial cells and in iris tissue of PACG patients. PLEKHA7 expression also correlated with the C risk allele of the sentinel SNP rs11024102 with the risk allele carrier groups having significantly reduced PLEKHA7 levels compared to non-risk allele carriers. Silencing of PLEKHA7 in human immortalized non-pigmented ciliary epithelium (h-iNPCE) and primary trabecular meshwork cells, which are intimately linked to BAB and aqueous humor outflow respectively, affected actin cytoskeleton organization...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28973398/neurodevelopmental-disease-associated-de-novo-mutations-and-rare-sequence-variants-affect-trio-gdp-gtp-exchange-factor-activity
#8
Sara M Katrancha, Yi Wu, Minsheng Zhu, Betty A Eipper, Anthony J Koleske, Richard E Mains
Bipolar disorder, schizophrenia, autism, and intellectual disability are complex neurodevelopmental disorders, debilitating millions of people. Therapeutic progress is limited by poor understanding of underlying molecular pathways. Using a targeted search, we identified an enrichment of de novo mutations in the gene encoding the 330-kDa triple functional domain (TRIO) protein associated with neurodevelopmental disorders. By generating multiple TRIO antibodies, we show that the smaller TRIO9 isoform is the major brain protein product, and its levels decrease after birth...
September 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28954861/the-balance-between-g%C3%AE-i-cdc42-rac-and-g%C3%AE-12-13-rhoa-pathways-determines-endothelial-barrier-regulation-by-sphingosine-1-phosphate
#9
Nathalie R Reinhard, Marieke Mastop, Taofei Yin, Yi Wu, Esmeralda K Bosma, Theodorus W J Gadella, Joachim Goedhart, Peter L Hordijk
The bioactive sphingolipid S1P is present in plasma, bound to carrier proteins, and is involved in many physiological processes, including angiogenesis, inflammatory responses and vascular stabilization. S1P can bind to several G-protein-coupled receptors (GPCRs) activating a number of different signalling networks. At present, the dynamics and relative importance of signalling events activated immediately downstream of GPCR activation are unclear. To examine this, we used a set of FRET-based biosensors for different RhoGTPases (Rac1, RhoA/B/C, Cdc42) as well as for heterotrimeric G-proteins in a series of live-cell imaging experiments in primary human endothelial cells...
September 27, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28949796/rhoa-rhob-and-rhoc-differentially-regulate-endothelial-barrier-function
#10
Manon C A Pronk, Jan S M van Bezu, Geerten P van Nieuw Amerongen, Victor W M van Hinsbergh, Peter L Hordijk
RhoGTPases are known regulators of intracellular actin dynamics that are important for maintaining endothelial barrier function. RhoA is most extensively studied as a key regulator of endothelial barrier function, however the function of the 2 highly homologous family-members (> 88%) RhoB and RhoC in endothelial barrier function is still poorly understood. This study aimed to determine whether RhoA, RhoB and RhoC have overlapping or distinct roles in barrier function and permeability in resting and activated endothelium...
September 26, 2017: Small GTPases
https://www.readbyqxmd.com/read/28927892/cd100-plexin-b2-promotes-the-inflammation-in-psoriasis-by-activating-nf-%C3%AE%C2%BAb-and-inflammasome-in-keratinocytes
#11
Chen Zhang, Chunying Xiao, Erle Dang, Jiao Cao, Zhenlai Zhu, Meng Fu, Xu Yao, Yufeng Liu, Boquan Jin, Gang Wang, Wei Li
Plexin-B2 (PlxnB2) and its ligand, CD100 (Semaphorin 4D), are originally identified as axon-guidance molecules that function during neuronal development; however, studies also showed that CD100-Plexins participate in various immune responses. In the present study, we found that the expression of PlxnB2 on keratinocytes was specifically increased in lesional skin of psoriasis patients, but not atopic dermatitis. Levels of soluble CD100 (sCD100) and membrane CD100 (mCD100) were elevated in sera of psoriasis patients and on keratinocytes of psoriatic skin, respectively...
September 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28919558/cellular-uptake-of-extracellular-vesicles-is-mediated-by-clathrin-independent-endocytosis-and-macropinocytosis
#12
Helena Costa Verdera, Jerney J Gitz-Francois, Raymond M Schiffelers, Pieter Vader
Recent evidence has established that extracellular vesicles (EVs), including exosomes and microvesicles, form an endogenous transport system through which biomolecules, including proteins and RNA, are exchanged between cells. This endows EVs with immense potential for drug delivery and regenerative medicine applications. Understanding the biology underlying EV-based intercellular transfer of cargo is of great importance for the development of EV-based therapeutics. Here, we sought to characterize the cellular mechanisms involved in EV uptake...
September 14, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28915620/prpf-overexpression-induces-drug-resistance-through-actin-cytoskeleton-rearrangement-and-epithelial-mesenchymal-transition
#13
Salman Ul Islam, Adeeb Shehzad, Jong Kyung Sonn, Young Sup Lee
Pre-mRNA processing factor (PRPF) 4B kinase belongs to the CDK-like kinase family, and is involved in pre-mRNA splicing, and in signal transduction. In this study, we observed that PRPF overexpression decreased the intracellular levels of reactive oxygen species, and inhibited resveratrol-induced apoptosis by activating the cell survival signaling proteins NFκB, ERK, and c-MYC in HCT116 human colon cancer cells. PRPF overexpression altered cellular morphology, and rearranged the actin cytoskeleton, by regulating the activity of Rho family proteins...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28911825/paving-the-rho-in-cancer-metastasis-rho-gtpases-and-beyond
#14
REVIEW
Sepp Jansen, Reinoud Gosens, Thomas Wieland, Martina Schmidt
Malignant carcinomas are often characterized by metastasis, the movement of carcinoma cells from a primary site to colonize distant organs. For metastasis to occur, carcinoma cells first must adopt a pro-migratory phenotype and move through the surrounding stroma towards a blood or lymphatic vessel. Currently, there are very limited possibilities to target these processes therapeutically. The family of Rho GTPases is an ubiquitously expressed division of GTP-binding proteins involved in the regulation of cytoskeletal dynamics and intracellular signaling...
September 11, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28855187/inhibition-of-smooth-muscle-contraction-and-arf-6-activity-by-the-inhibitor-for-cytohesin-gefs-secinh3-in-the-human-prostate
#15
Annika Herlemann, Patrick Keller, Melanie Schott, Alexander Tamalunas, Anna Ciotkowska, Beata Rutz, Yiming Wang, Qingfeng Yu, Raphaela Waidelich, Frank Strittmatter, Christian G Stief, Christian Gratzke, Martin Hennenberg
Prostate smooth muscle contraction is critical for etiology and treatment of male lower urinary tract symptoms (LUTS), and is promoted by small monomeric GTPases (RhoA, Rac). GTPases may be activated by guanosine nucleotide exchange factors (GEFs). GEFs of the cytohesin family may indirectly activate Rac, or ADP ribosolyation factor (ARF) GTPases directly. Here we investigated the expression of cytohesin family GEFs, and effects of the cytohesin inhibitor secinH3 on smooth muscle contraction and GTPase activities in human prostate tissues...
August 30, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28844950/mir-4516-a-microrna-downregulated-in-psoriasis-inhibits-keratinocyte-motility-by-targeting-fibronectin-integrin-%C3%AE-9-signaling
#16
Shruti Chowdhari, Kabir Sardana, Neeru Saini
Psoriasis is recognized as a T cell mediated inflammatory hyperproliferative skin disorder. Several microRNAs (miRNAs) have been implicated in the pathogenesis of psoriasis however, understanding of their mechanistic involvement remains unclear. Previously, we have shown that PUVA induced miR-4516 downregulates signal transducer and activator of transcription 3 (STAT3) by direct binding to its 3' untranslated region (3'UTR) and suppresses STAT3 downstream genes (Bcl xl, Cyclin D1). Here, we demonstrate for the first time that expression of miR-4516 is significantly downregulated in psoriatic skin...
August 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28841878/the-role-of-lutheran-basal-cell-adhesion-molecule-in-human-bladder-carcinogenesis
#17
Hong-Yi Chang, Hsin-Mei Chang, Tsung-Jung Wu, Chang-Yao Chaing, Tzong-Shin Tzai, Hong-Lin Cheng, Giri Raghavaraju, Nan-Haw Chow, Hsiao-Sheng Liu
BACKGROUND: Lutheran/basal cell adhesion molecule (Lu/BCAM) is a membrane bound glycoprotein. This study was performed to investigate the role and downstream signaling pathway of Lu/BCAM in human bladder tumorigenesis. METHODS: Five human bladder cancer (E6, RT4, TSGH8301, TCCSUP and J82), one stable mouse fibroblast cell line (NIH-Lu) expressing Lu/BCAM transgene and sixty human uroepithelial carcinoma specimens were analyzed by real-time PCR, immunohistochemistry (IHC), immunofluorescence (IFA) staining, Western blotting and promoter luciferase assay for Lu/BCAM, respectively...
August 26, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28811522/the-lichen-secondary-metabolite-atranorin-suppresses-lung-cancer-cell-motility-and-tumorigenesis
#18
Rui Zhou, Yi Yang, So-Yeon Park, Thanh Thi Nguyen, Young-Woo Seo, Kyung Hwa Lee, Jae Hyuk Lee, Kyung Keun Kim, Jae-Seoun Hur, Hangun Kim
Lichens are symbiotic organisms that produce various secondary metabolites. Here, different lichen extracts were examined to identify secondary metabolites with anti-migratory activity against human lung cancer cells. Everniastrum vexans had the most potent inhibitory activity, and atranorin was identified as an active subcomponent of this extract. Atranorin suppressed β-catenin-mediated TOPFLASH activity by inhibiting the nuclear import of β-catenin and downregulating β-catenin/LEF and c-jun/AP-1 downstream target genes such as CD44, cyclin-D1 and c-myc...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28767310/disrupted-irf6-nme1-2-complexes-as-a-cause-of-cleft-lip-palate
#19
M T Parada-Sanchez, E Y Chu, L L Cox, S S Undurty, J M Standley, J C Murray, T C Cox
Mutations and common polymorphisms in interferon regulatory factor 6 ( IRF6) are associated with both syndromic and nonsyndromic forms of cleft lip/palate (CLP). To date, much of the focus on this transcription factor has been on identifying its direct targets and the gene regulatory network in which it operates. Notably, however, IRF6 is found predominantly in the cytoplasm, with its import into the nucleus tightly regulated like other members of the IRF family. To provide further insight into the role of IRF6 in the pathogenesis of CLP, we sought to identify direct IRF6 protein interactors using a combination of yeast 2-hybrid screens and co-immunoprecipitation assays...
October 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28765773/astaxanthin-induces-migration-in-human-skin-keratinocytes-via-rac1-activation-and-rhoa-inhibition
#20
Dakanda Ritto, Supita Tanasawet, Sawana Singkhorn, Wanwimol Klaypradit, Pilaiwanwadee Hutamekalin, Varomyalin Tipmanee, Wanida Sukketsiri
BACKGROUND/OBJECTIVES: Re-epithelialization has an important role in skin wound healing. Astaxanthin (ASX), a carotenoid found in crustaceans including shrimp, crab, and salmon, has been widely used for skin protection. Therefore, we investigated the effects of ASX on proliferation and migration of human skin keratinocyte cells and explored the mechanism associated with that migration. MATERIAL/METHOD: HaCaT keratinocyte cells were exposed to 0.25-1 µg/mL of ASX...
August 2017: Nutrition Research and Practice
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