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https://www.readbyqxmd.com/read/28743335/-regulation-of-paxillin-tyrosine-phosphorylation-via-inhibition-of-c-abl-kinase-to-protect-ventilator-induce-lung-injury-in-vivo-in-rats
#1
Rong Zhong, Jun Xiao, Chunguang Dai, Zhihui Yu
OBJECTIVE: To determine whether the inhibition of paxillin tyrosine residues 31 and tyrosine residues 118 (Pxn Y31 and Pxn Y118) phosphorylation via inhibition of c-Abl kinase will effectively block its downstream effector molecules vessel endothelium-cadherin (VE-cad), and whether Rho/Rho kinase activation which will induce the vascular barrier dysfunction. METHODS: Ninety healthy male Sprague-Dawley (SD) rats were randomly divided into nine groups (each n =10)...
July 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28742002/cdc42-activation-state-affects-its-localization-and-protein-levels-in-fission-yeast
#2
Miguel Estravís, Sergio Antonio Rincón, Elvira Portales, Pilar Pérez, Beatriz Santos
Rho GTPases control polarized cell growth and are well-known regulators of exocytic and endocytic processes. Cdc42 is an essential GTPase, conserved from yeast to humans, that is critical for cell polarization. Cdc42 is negatively regulated by the GTPase-activating proteins (GAPs) and the GDP dissociation inhibitors (GDIs), and positively regulated by guanine nucleotide exchange factors (GEFs). Cdc42 GTPase can be found in a GTP- or GDP-bound state, which determines the ability to bind downstream effector proteins and activate signalling pathways...
July 26, 2017: Microbiology
https://www.readbyqxmd.com/read/28712859/tyr42-phosphorylation-of-rhoa-gtpase-promotes-tumorigenesis-through-nuclear-factor-nf-%C3%AE%C2%BAb
#3
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 for ROS in tumorigenesis have not been well established. In this study, hydrogen peroxide activated nuclear factor-κB (NF-κB) and RhoA GTPase. In particular, we found that hydrogen peroxide lead to phosphorylation of RhoA at Tyr42 via tyrosine kinase Src. Phospho-Tyr42 (p-Tyr42) residue of RhoA is a binding site for Vav2, a guanine nucleotide exchange factor (GEF), which then activates p-Tyr42 form of RhoA...
July 14, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28701658/drosophila-dock-family-protein-zizimin-involves-in-pigment-cell-differentiation-in-pupal-retinae
#4
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/28657426/oncogenic-ect2-signaling-regulates-rrna-synthesis-in-nsclc
#5
Verline Justilien, Kayla C Lewis, Nicole R Murray, Alan P Fields
The Rho GTPase family members Rac1, Cdc42 and RhoA play key contributory roles in the transformed phenotype of human cancers. Epithelial Cell Transforming Sequence 2 (Ect2), a guanine nucleotide exchange factor (GEF) for these Rho GTPases, has also been implicated in a variety of human cancers. We have shown that Ect2 is frequently overexpressed in both major forms of non-small cell lung cancer (NSCLC), lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC), which together make up approximately 70% of all lung cancer diagnoses...
June 28, 2017: Small GTPases
https://www.readbyqxmd.com/read/28652571/discovery-of-long-range-inhibitory-signaling-to-ensure-single-axon-formation
#6
Tetsuya Takano, Mengya Wu, Shinichi Nakamuta, Honda Naoki, Naruki Ishizawa, Takashi Namba, Takashi Watanabe, Chundi Xu, Tomonari Hamaguchi, Yoshimitsu Yura, Mutsuki Amano, Klaus M Hahn, Kozo Kaibuchi
A long-standing question in neurodevelopment is how neurons develop a single axon and multiple dendrites from common immature neurites. Long-range inhibitory signaling from the growing axon is hypothesized to prevent outgrowth of other immature neurites and to differentiate them into dendrites, but the existence and nature of this inhibitory signaling remains unknown. Here, we demonstrate that axonal growth triggered by neurotrophin-3 remotely inhibits neurite outgrowth through long-range Ca(2+) waves, which are delivered from the growing axon to the cell body...
June 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28644070/particulate-matter-disrupts-human-lung-endothelial-cell-barrier-integrity-via-rho-dependent-pathways
#7
Ting Wang, Yuka Shimizu, Xiaomin Wu, Gabriel T Kelly, Xiaoyan Xu, Lichun Wang, Zhongqing Qian, Yin Chen, Joe G N Garcia
Increased exposure to ambient particulate matter (PM) is associated with elevated morbidity and mortality in patients with cardiopulmonary diseases and cancer. We and others have shown that PM induces lung microvascular barrier dysfunction which potentially enhances the systemic toxicity of PM. However, the mechanisms by which PM disrupts vascular endothelial integrity remain incompletely explored. We hypothesize that PM induces endothelial cell (EC) cytoskeleton rearrangement via Rho GTPase-dependent pathways to facilitate vascular hyperpermeability...
June 23, 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28585695/the-rhogap-myo9b-promotes-bone-growth-by-mediating-osteoblastic-responsiveness-to-igf-1
#8
Brooke K McMichael, Yong-Hoon Jeong, Justin A Auerbach, Cheol-Min Han, Ryan Sedlar, Vikram Shettigar, Martin Bähler, Sudha Agarwal, Do-Gyoon Kim, Beth S Lee
The Ras homolog A (RhoA) subfamily of Rho guanosine triphosphatases (GTPases) regulates actin-based cellular functions in bone such as differentiation, migration, and mechanotransduction. Polymorphisms or genetic ablation of RHOA and some of its regulatory guanine exchange factors (GEFs) have been linked to poor bone health in humans and mice, but the effects of RhoA-specific GTPase-activating proteins (GAPs) on bone quality have not yet been identified. Therefore, we examined the consequences of RhoGAP Myo9b gene knockout on bone growth, phenotype, and cellular activity...
June 6, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28554775/zonula-occludens-2-regulates-rho-proteins-activity-and-the-development-of-epithelial-cytoarchitecture-and-barrier-function
#9
Arturo Raya-Sandino, Alejandro Castillo-Kauil, Alaide Domínguez-Calderón, Lourdes Alarcón, David Flores-Benitez, Francisco Cuellar-Perez, Bruno López-Bayghen, Bibiana Chávez-Munguía, José Vázquez-Prado, Lorenza González-Mariscal
Silencing Zonula occludens 2 (ZO-2), a tight junctions (TJ) scaffold protein, in epithelial cells (MDCK ZO-2 KD) triggers: 1) Decreased cell to substratum attachment, accompanied by reduced expression of claudin-7 and integrin β1, and increased vinculin recruitment to focal adhesions and stress fibers formation; 2) Lowered cell-cell aggregation and appearance of wider intercellular spaces; 3) Increased RhoA/ROCK activity, mediated by GEF-HI recruitment to cell borders by cingulin; 4) Increased Cdc42 activity, mitotic spindle disorientation and the appearance of cysts with multiple lumens; 5) Increased Rac and cofilin activity, multiple lamellipodia formation and random cell migration but increased wound closure; 6) Diminished cingulin phosphorylation and disappearance of planar network of microtubules at the TJ region; and 7) Increased transepithelial electrical resistance at steady state, coupled to an increased expression of ZO-1 and claudin-4 and a decreased expression of claudin-2 and paracingulin...
May 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28539404/analysis-of-interphase-node-proteins-in-fission-yeast-by-quantitative-and-super-resolution-fluorescence-microscopy
#10
Matthew Akamatsu, Yu Lin, Joerg Bewersdorf, Thomas D Pollard
We used quantitative confocal microscopy and FPALM super resolution microscopy of live fission yeast to investigate the structures and assembly of two types of interphase nodes, multiprotein complexes associated with the plasma membrane that merge together and mature into the precursors of the cytokinetic contractile ring. During the long G2 phase of the cell cycle seven different interphase node proteins maintain constant concentrations as they accumulate in proportion to cell volume. During mitosis the total numbers of type 1 node proteins (cell cycle kinases Cdr1p, Cdr2p, Wee1p, and anillin Mid1p) are constant even when the nodes disassemble...
May 24, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28521592/molecular-perturbation-strategies-to-examine-spatiotemporal-features-of-rho-gef-and-rho-gtpase-activity-in-living-cells
#11
Joachim Goedhart, Jakobus van Unen
Much of our current knowledge of Rho GTPase networks and the regulation by Rho guanine exchange factors (Rho GEFs) and Rho GTPase activating proteins (Rho GAPs) is based on population-based techniques. Over the last decades, technologies that enable single cell analysis with high spatial and temporal resolution have revealed that Rho GTPase activity in cells is regulated on second timescales and at submicrometer length scales. Therefore, perturbation methods with matching spatial and temporal resolution are crucial to further our understanding of Rho GTPase signaling...
May 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28512143/diverse-roles-of-guanine-nucleotide-exchange-factors-in-regulating-collective-cell-migration
#12
Assaf Zaritsky, Yun-Yu Tseng, M Angeles Rabadán, Shefali Krishna, Michael Overholtzer, Gaudenz Danuser, Alan Hall
Efficient collective migration depends on a balance between contractility and cytoskeletal rearrangements, adhesion, and mechanical cell-cell communication, all controlled by GTPases of the RHO family. By comprehensive screening of guanine nucleotide exchange factors (GEFs) in human bronchial epithelial cell monolayers, we identified GEFs that are required for collective migration at large, such as SOS1 and β-PIX, and RHOA GEFs that are implicated in intercellular communication. Down-regulation of the latter GEFs differentially enhanced front-to-back propagation of guidance cues through the monolayer and was mirrored by down-regulation of RHOA expression and myosin II activity...
June 5, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28489960/swap70-is-a-universal-gef-like-adapter-for-tethering-actin-to-phagosomes
#13
Maksim V Baranov, Natalia H Revelo, Daniëlle R J Verboogen, Martin Ter Beest, Geert van den Bogaart
We recently identified a key role for SWAP70 as the tethering factor stabilizing F-actin filaments on the surface of phagosomes in human dendritic cells by interacting both with Rho-family GTPases and the lipid phosphatidylinositol (3,4)-bisphosphate. In this study, we aimed to investigate whether this role of SWAP70 was general among immune phagocytes. Our data reveal that SWAP70 is recruited to early phagosomes of macrophages and dendritic cells from both human and mouse. The putative inhibitor of SWAP70 sanguinarine blocked phagocytosis and F-actin polymerization, supporting a key role for SWAP70 in phagocytosis as demonstrated previously with knock-down...
May 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28472098/t1r3-homomeric-sweet-taste-receptor-regulates-adipogenesis-through-g%C3%AE-s-mediated-microtubules-disassembly-and-rho-activation-in-3t3-l1-cells
#14
Yosuke Masubuchi, Yuko Nakagawa, Johan Medina, Masahiro Nagasawa, Itaru Kojima, Mark M Rasenick, Takeshi Inagaki, Hiroshi Shibata
We previously reported that 3T3-L1 cells express a functional sweet taste receptor possibly as a T1R3 homomer that is coupled to Gs and negatively regulates adipogenesis by a Gαs-mediated but cAMP-independent mechanism. Here, we show that stimulation of this receptor with sucralose or saccharin induced disassembly of the microtubules in 3T3-L1 preadipocytes, which was attenuated by overexpression of the dominant-negative mutant of Gαs (Gαs-G226A). In contrast, overexpression of the constitutively active mutant of Gαs (Gαs-Q227L) as well as treatment with cholera toxin or isoproterenol but not with forskolin caused disassembly of the microtubules...
2017: PloS One
https://www.readbyqxmd.com/read/28418645/brain-region-and-isoform-specific-phosphorylation-alters-kalirin-sh2-domain-interaction-sites-and-calpain-sensitivity
#15
Megan B Miller, Yan Yan, Kazuya Machida, Drew D Kiraly, Aaron D Levy, Yi I Wu, TuKiet T Lam, Thomas Abbott, Anthony J Koleske, Betty A Eipper, Richard E Mains
Kalirin7 (Kal7), a postsynaptic Rho GDP/GTP exchange factor (RhoGEF), plays a crucial role in long-term potentiation and in the effects of cocaine on behavior and spine morphology. The KALRN gene has been linked to schizophrenia and other disorders of synaptic function. Mass spectrometry was used to quantify phosphorylation at 26 sites in Kal7 from individual adult rat nucleus accumbens and prefrontal cortex before and after exposure to acute or chronic cocaine. Region- and isoform-specific phosphorylation was observed along with region-specific effects of cocaine on Kal7 phosphorylation...
July 19, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28389580/the-mgcracgap-sxip-motif-tethers-centralspindlin-to-microtubule-plus-ends-in-xenopus-laevis
#16
Elaina B Breznau, Megan Murt, T Lynne Blasius, Kristen J Verhey, Ann L Miller
Centralspindlin, a complex of the kinesin-6-family member MKLP1 and MgcRacGAP (also known as Kif23 and Racgap1, respectively), is required for cytokinesis and cell-cell junctions. During anaphase, Centralspindlin accumulates at overlapping central spindle microtubules and directs contractile ring formation by recruiting the GEF Ect2 to the cell equator to activate RhoA. We found that MgcRacGAP localized to the plus ends of equatorial astral microtubules during cytokinesis in Xenopus laevis embryos. How MgcRacGAP is stabilized at microtubule plus ends is unknown...
May 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28356423/phosphorylated-cortactin-recruits-vav2-guanine-nucleotide-exchange-factor-to-activate-rac3-and-promote-invadopodial-function-in-invasive-breast-cancer-cells
#17
Brian J Rosenberg, Hava Gil-Henn, Christopher C Mader, Tiffany Halo, Taofei Yin, John Condeelis, Kazuya Machida, Yi I Wu, Anthony J Koleske
Breast carcinoma cells use specialized, actin-rich protrusions called invadopodia to degrade and invade through the extracellular matrix. Phosphorylation of the actin nucleation-promoting factor and actin-stabilizing protein cortactin downstream of the epidermal growth factor receptor-Src-Arg kinase cascade is known to be a critical trigger for invadopodium maturation and subsequent cell invasion in breast cancer cells. The functions of cortactin phosphorylation in this process, however, are not completely understood...
May 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28334931/rgf1p-rho1p-gef-is-required-for-double-strand-break-repair-in-fission-yeast
#18
Elvira Manjón, Tomás Edreira, Sofía Muñoz, Yolanda Sánchez
Rho GTPases are conserved molecules that control cytoskeletal dynamics. These functions are expedited by Rho GEFs that stimulate the release of GDP to enable GTP binding, thereby allowing Rho proteins to initiate intracellular signaling. How Rho GEFs and Rho GTPases protect cells from DNA damage is unknown. Here, we explore the extreme sensitivity of a deletion mutation in the Rho1p exchange factor Rgf1p to the DNA break/inducing antibiotic phleomycin (Phl). The Rgf1p mutant cells are defective in reentry into the cell cycle following the induction of severe DNA damage...
May 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28304230/modular-regulation-of-rho-family-gtpases-in-development
#19
Marlis Denk-Lobnig, Adam C Martin
Rho family GTPase signaling regulates the actin cytoskeleton and is critical for behaviors that range from the cell to tissue-scale. A theme in Rho GTPase biology is that there are many more regulators, such as guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), than GTPases themselves. Here, we review different, modular cases where GEFs and GAPs function together to elicit precise spatial and temporal control of signaling. We focus on examples from metazoan development, where precise regulation of Rho GTPases is critical for proper tissue form and function...
March 17, 2017: Small GTPases
https://www.readbyqxmd.com/read/28298491/cyk-4-regulates-rac-but-not-rho-during-cytokinesis
#20
Yelena Zhuravlev, Sophia M Hirsch, Shawn N Jordan, Julien Dumont, Mimi Shirasu-Hiza, Julie C Canman
Cytokinesis is driven by constriction of an actomyosin contractile ring that is controlled by Rho-family small GTPases. Rho, activated by the guanine-nucleotide exchange factor ECT-2, is upstream of both myosin-II activation and diaphanous formin-mediated filamentous actin (f-actin) assembly, which drive ring constriction. The role for Rac and its regulators is more controversial, but, based on the finding that Rac inactivation can rescue cytokinesis failure when the GTPase-activating protein (GAP) CYK-4 is disrupted, Rac activity was proposed to be inhibitory to contractile ring constriction and thus specifically inactivated by CYK-4 at the division plane...
May 1, 2017: Molecular Biology of the Cell
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