Journal articles: 'ROC2'

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Donaldson, Timothy D., Maher A. Noureddine, Patrick J. Reynolds, William Bradford, and Robert J. Duronio. "Targeted Disruption of Drosophila Roc1b Reveals Functional Differences in the Roc Subunit of Cullin-dependent E3 Ubiquitin Ligases." Molecular Biology of the Cell 15, no. 11 (November 2004): 4892–903. http://dx.doi.org/10.1091/mbc.e04-03-0180.

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Cullin-dependent ubiquitin ligases regulate a variety of cellular and developmental processes by recruiting specific proteins for ubiquitin-mediated degradation. Cullin proteins form a scaffold for two functional modules: a catalytic module comprised of a small RING domain protein Roc1/Rbx1 and a ubiquitin-conjugating enzyme (E2), and a substrate recruitment module containing one or more proteins that bind to and bring the substrate in proximity to the catalytic module. Here, we present evidence that the three Drosophila Roc proteins are not functionally equivalent. Mutation of Roc1a causes lethality that cannot be rescued by expression of Roc1b or Roc2 by using the Roc1a promoter. Roc1a mutant cells hyperaccumulate Cubitus interruptus, a transcription factor that mediates Hedgehog signaling. This phenotype is not rescued by expression of Roc2 and only partially by expression of Roc1b. Targeted disruption of Roc1b causes male sterility that is partially rescued by expression of Roc1a by using the Roc1b promoter, but not by similar expression of Roc2. These data indicate that Roc proteins play nonredundant roles during development. Coimmunoprecipitation followed by Western or mass spectrometric analysis indicate that the three Roc proteins preferentially bind certain Cullins, providing a possible explanation for the distinct biological activities of each Drosophila Roc/Rbx.

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Jia, L., J. Yang, X. Hao, M. Zheng, H. He, X. Xiong, L. Xu, and Y. Sun. "Validation of SAG/RBX2/ROC2 E3 Ubiquitin Ligase as an Anticancer and Radiosensitizing Target." Clinical Cancer Research 16, no. 3 (January 26, 2010): 814–24. http://dx.doi.org/10.1158/1078-0432.ccr-09-1592.

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Tan, Mingjia, Hua Li, and Yi Sun. "Inactivation of Sag/Rbx2/Roc2 E3 Ubiquitin Ligase Triggers Senescence and Inhibits Kras-Induced Immortalization." Neoplasia 17, no. 1 (January 2015): 114–23. http://dx.doi.org/10.1016/j.neo.2014.11.008.

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Sun, Yi, and Hua Li. "Functional characterization of SAG/RBX2/ROC2/RNF7, an antioxidant protein and an E3 ubiquitin ligase." Protein & Cell 4, no. 2 (November 8, 2012): 103–16. http://dx.doi.org/10.1007/s13238-012-2105-7.

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Tan, M., Q. Gu, H. He, D. Pamarthy, G. L. Semenza, and Y. Sun. "SAG/ROC2/RBX2 is a HIF-1 target gene that promotes HIF-1α ubiquitination and degradation." Oncogene 27, no. 10 (September 10, 2007): 1404–11. http://dx.doi.org/10.1038/sj.onc.1210780.

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Tan, M., H. Li, and Y. Sun. "Endothelial deletion of Sag/Rbx2/Roc2 E3 ubiquitin ligase causes embryonic lethality and blocks tumor angiogenesis." Oncogene 33, no. 44 (November 11, 2013): 5211–20. http://dx.doi.org/10.1038/onc.2013.473.

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Tan, Mingjia, Yongchao Zhao, Sun-Jung Kim, Margaret Liu, Lijun Jia, Thomas L. Saunders, Yuan Zhu, and Yi Sun. "SAG/RBX2/ROC2 E3 Ubiquitin Ligase Is Essential for Vascular and Neural Development by Targeting NF1 for Degradation." Developmental Cell 21, no. 6 (December 2011): 1062–76. http://dx.doi.org/10.1016/j.devcel.2011.09.014.

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Kim, Yun-Sook, Jae-Yong Lee, Mi-Young Son, Wan Park, and Young-Seuk Bae. "Phosphorylation of Threonine 10 on CKBBP1/SAG/ROC2/Rbx2 by Protein Kinase CKII Promotes the Degradation of IκBα and p27Kip1." Journal of Biological Chemistry 278, no. 31 (May 13, 2003): 28462–69. http://dx.doi.org/10.1074/jbc.m302584200.

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9

Gu, Qingyang, G. Tim Bowden, Daniel Normolle, and Yi Sun. "SAG/ROC2 E3 ligase regulates skin carcinogenesis by stage-dependent targeting of c-Jun/AP1 and IκB-α/NF-κB." Journal of Cell Biology 178, no. 6 (September 10, 2007): 1009–23. http://dx.doi.org/10.1083/jcb.200612067.

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Sensitive to apoptosis gene (SAG)/regulator of cullins-2–Skp1-cullin–F-box protein (SCF) E3 ubiquitin ligase regulates cellular functions through ubiquitination and degradation of protein substrates. We report that, when expressed in mouse epidermis driven by the K14 promoter, SAG inhibited TPA-induced c-Jun levels and activator protein-1 (AP-1) activity in both in vitro primary culture, in vivo transgenic mice, and an AP-1– luciferase reporter mouse model. After AP-1 inactivation, epidermal proliferation induced by 7,12-dimethylbenz(a)-anthracene/12-O-tetradecanoylphorbol-13-acetate at the early stage of carcinogenesis was substantially inhibited. Later stage tumor formation was also substantially inhibited with prolonged latency and reduced frequency of tumor formation. Interestingly, SAG expression increased tumor size, not because of accelerated proliferation, but caused by reduced apoptosis resulting, at least in part, from nuclear factor κB (NF-κB) activation. Thus, SAG, in a manner depending on the availability of F-box proteins, demonstrated early-stage suppression of tumor formation by promoting c-Jun degradation, thereby inhibiting AP-1, and later-stage enhancement of tumor growth, by promoting inhibitor of κBα degradation to activate NF-κB and inhibit apoptosis.

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Swaroop, Manju, Mark Gosink, and Yi Sun. "SAG/ROC2/Rbx2/Hrt2, a Component of SCF E3 Ubiquitin Ligase: Genomic Structure, a Splicing Variant, and Two Family Pseudogenes." DNA and Cell Biology 20, no. 7 (July 2001): 425–34. http://dx.doi.org/10.1089/104454901750361488.

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Tan, Mingjia, Yueming Zhu, Jordan Kovacev, Yongchao Zhao, Zhen-Qiang Pan, Douglas R. Spitz, and Yi Sun. "Disruption of Sag/Rbx2/Roc2 induces radiosensitization by increasing ROS levels and blocking NF-κB activation in mouse embryonic stem cells." Free Radical Biology and Medicine 49, no. 6 (September 15, 2010): 976–83. http://dx.doi.org/10.1016/j.freeradbiomed.2010.05.030.

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Zhang, Shizhen, Yanwen Shen, Hua Li, Chao Bi, Yilun Sun, Xiufang Xiong, Wenyi Wei, and Yi Sun. "The Negative Cross-Talk between SAG/RBX2/ROC2 and APC/C E3 Ligases in Regulation of Cell Cycle Progression and Drug Resistance." Cell Reports 32, no. 10 (September 2020): 108102. http://dx.doi.org/10.1016/j.celrep.2020.108102.

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He, Hongbin, Qingyang Gu, Min Zheng, Daniel Normolle, and Yi Sun. "SAG/ROC2/RBX2 E3 ligase promotes UVB-induced skin hyperplasia, but not skin tumors, by simultaneously targeting c-Jun/AP-1 and p27." Carcinogenesis 29, no. 4 (February 6, 2008): 858–65. http://dx.doi.org/10.1093/carcin/bgn021.

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Huang, Yuanhui, Hangjun Duan, and Yi Sun. "Elevated expression of SAG/ROC2/Rbx2/Hrt2 in human colon carcinomas: SAG does not induce neoplastic transformation, but antisense SAG transfection inhibits tumor cell growth." Molecular Carcinogenesis 30, no. 1 (January 2001): 62–70. http://dx.doi.org/10.1002/1098-2744(200101)30:1<62::aid-mc1014>3.0.co;2-a.

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15

Gu, Qingyang, Mingjia Tan, and Yi Sun. "SAG/ROC2/Rbx2 Is a Novel Activator Protein-1 Target that Promotes c-Jun Degradation and Inhibits 12-O-Tetradecanoylphorbol-13-Acetate–Induced Neoplastic Transformation." Cancer Research 67, no. 8 (April 15, 2007): 3616–25. http://dx.doi.org/10.1158/0008-5472.can-06-4020.

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Swaroop, Manju, Yixin Wang, Paul Miller, Hangjun Duan, Tim Jatkoe, Steven J. Madore, and Yi Sun. "Yeast homolog of human SAG/ROC2/Rbx2/Hrt2 is essential for cell growth, but not for germination: chip profiling implicates its role in cell cycle regulation." Oncogene 19, no. 24 (June 2000): 2855–66. http://dx.doi.org/10.1038/sj.onc.1203635.

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17

Duan, Hangjun, Lyuben M. Tsvetkov, Yalun Liu, Ying Song, Manju Swaroop, Rong Wen, Hsiang-Fu Kung, Hui Zhang, and Yi Sun. "Promotion of S-phase entry and cell growth under serum starvation by SAG/ROC2/Rbx2/Hrt2, an E3 ubiquitin ligase component: Association with inhibition of p27 accumulation." Molecular Carcinogenesis 30, no. 1 (January 2001): 37–46. http://dx.doi.org/10.1002/1098-2744(200101)30:1<37::aid-mc1011>3.0.co;2-7.

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18

Ali, Naima Ould, Josette Jeusset, Eric Larquet, Eric Le Cam, Boris Belitsky, Abraham L. Sonenshein, Tarek Msadek, and Michel Débarbouillé. "Specificity of the interaction of RocR with the rocG–rocA intergenic region in Bacillus subtilis." Microbiology 149, no. 3 (March 1, 2003): 739–50. http://dx.doi.org/10.1099/mic.0.26013-0.

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Takeda, Yusuke, Keiichiro Matoba, Daiji Kawanami, Yosuke Nagai, Tomoyo Akamine, Sho Ishizawa, Yasushi Kanazawa, Tamotsu Yokota, and Kazunori Utsunomiya. "ROCK2 Regulates Monocyte Migration and Cell to Cell Adhesion in Vascular Endothelial Cells." International Journal of Molecular Sciences 20, no. 6 (March 16, 2019): 1331. http://dx.doi.org/10.3390/ijms20061331.

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The small GTPase Rho and its downstream effector, Rho-kinase (ROCK), regulate various cellular functions, including organization of the actin cytoskeleton, cell adhesion and migration. A pro-inflammatory lipid mediator, lysophosphatidic acid (LPA), is a potent activator of the Rho/ROCK signalling pathway and has been shown to induce the expression of chemokines and cell adhesion molecules (CAMs). In the present study, we aimed to elucidate the precise mechanism by which ROCK regulates LPA-induced expressions and functions of chemokines and CAMs. We observed that ROCK blockade reduced LPA-induced phosphorylation of IκBα and inhibited NF-κB RelA/p65 phosphorylation, leading to attenuation of RelA/p65 nuclear translocation. Furthermore, small interfering RNA-mediated ROCK isoform knockdown experiments revealed that LPA induces the expression of monocyte chemoattractant protein-1 (MCP-1) and E-selectin via ROCK2 in human aortic endothelial cells (HAECs). Importantly, we found that ROCK2 but not ROCK1 controls LPA-induced monocytic migration and monocyte adhesion toward endothelial cells. These findings demonstrate that ROCK2 is a key regulator of endothelial inflammation. We conclude that targeting endothelial ROCK2 is potentially effective in attenuation of atherosclerosis.

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Nagai, Yosuke, Keiichiro Matoba, Daiji Kawanami, Yusuke Takeda, Tomoyo Akamine, Sho Ishizawa, Yasushi Kanazawa, Tamotsu Yokota, Kazunori Utsunomiya, and Rimei Nishimura. "ROCK2 regulates TGF-β-induced expression of CTGF and profibrotic genes via NF-κB and cytoskeleton dynamics in mesangial cells." American Journal of Physiology-Renal Physiology 317, no. 4 (October 1, 2019): F839—F851. http://dx.doi.org/10.1152/ajprenal.00596.2018.

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The small GTPase Rho and its effector Rho kinase (ROCK) are involved in the pathogenesis of diabetic kidney disease. Rho kinase has two isoforms: ROCK1 and ROCK2. However, it remains unclear which is mainly involved in the progression of diabetic glomerulosclerosis and the regulation of profibrotic mediators. Glomeruli isolated from type 2 diabetic db/ db mice demonstrated increased gene expression of transforming growth factor (TGF)-β and its downstream profibrotic mediators. Chemical inhibition of ROCK suppressed the expression of profibrotic mediators in both isolated glomeruli and cultured mesangial cells. An investigation of mechanisms underlying this observation revealed activated ROCK functions through the phosphorylation of JNK and Erk and the nuclear translocation of NF-κB via actin dynamics. Knockdown by siRNA against ROCK1 and ROCK2 showed that ROCK2 but not ROCK1 controls this fibrotic machinery. Further in vivo experiments showed that ROCK2 activity in the renal cortex of db/ db mice was elevated compared with control db/ m mice. Importantly, oral administration of ROCK2 inhibitor attenuated renal ROCK2 activity, albuminuria, and glomerular fibrosis in db/ db mice. These observations indicate that ROCK2 is a key player in the development of diabetic renal injury. Glomerular ROCK2 may be a potential therapeutic target for the treatment of diabetic kidney disease.

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Chaturvedi, Lakshmi S., Harold M. Marsh, and Marc D. Basson. "Role of RhoA and its effectors ROCK and mDia1 in the modulation of deformation-induced FAK, ERK, p38, and MLC motogenic signals in human Caco-2 intestinal epithelial cells." American Journal of Physiology-Cell Physiology 301, no. 5 (November 2011): C1224—C1238. http://dx.doi.org/10.1152/ajpcell.00518.2010.

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Repetitive deformation enhances intestinal epithelial migration across tissue fibronectin. We evaluated the contribution of RhoA and its effectors Rho-associated kinase (ROK/ROCK) and mammalian diaphanous formins (mDia1) to deformation-induced intestinal epithelial motility across fibronectin and the responsible focal adhesion kinase (FAK), extracellular signal-regulated kinase (ERK), p38, and myosin light chain (MLC) signaling. We reduced RhoA, ROCK1, ROCK2, and mDia1 by smart-pool double-stranded short-interfering RNAs (siRNA) and pharmacologically inhibited RhoA, ROCK, and FAK in human Caco-2 intestinal epithelial monolayers on fibronectin-coated membranes subjected to 10% repetitive deformation at 10 cycles/min. Migration was measured by wound closure. Stimulation of migration by deformation was prevented by exoenzyme C3, Y27632, or selective RhoA, ROCK1, and ROCK2 or mDia1 siRNAs. RhoA, ROCK inhibition, or RhoA, ROCK1, ROCK2, mDia1, and FAK reduction by siRNA blocked deformation-induced nuclear ERK phosphorylation without preventing ERK phosphorylation in the cytoplasmic protein fraction. Furthermore, RhoA, ROCK inhibition or RhoA, ROCK1, ROCK2, and mDia1 reduction by siRNA also blocked strain-induced FAK-Tyr925, p38, and MLC phosphorylation. These results suggest that RhoA, ROCK, mDia1, FAK, ERK, p38, and MLC all mediate the stimulation of intestinal epithelial migration by repetitive deformation. This pathway may be an important target for interventions to promote mechanotransduced mucosal healing during inflammation.

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Kasahara, David I., Joel A. Mathews, Chan Y. Park, Youngji Cho, Gabrielle Hunt, Allison P. Wurmbrand, James K. Liao, and Stephanie A. Shore. "ROCK insufficiency attenuates ozone-induced airway hyperresponsiveness in mice." American Journal of Physiology-Lung Cellular and Molecular Physiology 309, no. 7 (October 1, 2015): L736—L746. http://dx.doi.org/10.1152/ajplung.00372.2014.

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Ozone causes airway hyperresponsiveness (AHR) and pulmonary inflammation. Rho kinase (ROCK) is a key regulator of smooth muscle cell contraction and inflammatory cell migration. To determine the contribution of the two ROCK isoforms ROCK1 and ROCK2 to ozone-induced AHR, we exposed wild-type, ROCK1+/−, and ROCK2+/− mice to air or ozone (2 ppm for 3 h) and evaluated mice 24 h later. ROCK1 or ROCK2 haploinsufficiency did not affect airway responsiveness in air-exposed mice but significantly reduced ozone-induced AHR, with a greater reduction in ROCK2+/− mice despite increased bronchoalveolar lavage (BAL) inflammatory cells in ROCK2+/− mice. Compared with wild-type mice, ozone-induced increases in BAL hyaluronan, a matrix protein implicated in ozone-induced AHR, were lower in ROCK1+/− but not ROCK2+/− mice. Ozone-induced increases in other inflammatory moieties reported to contribute to ozone-induced AHR (IL-17A, osteopontin, TNFα) were not different in wild-type vs. ROCK1+/− or ROCK2+/− mice. We also observed a dose-dependent reduction in ozone-induced AHR after treatment with the ROCK1/ROCK2 inhibitor fasudil, even though fasudil was administered after induction of inflammation. Ozone increased pulmonary expression of ROCK2 but not ROCK1 or RhoA. A ROCK2 inhibitor, SR3677, reduced contractile forces in primary human airway smooth muscle cells, confirming a role for ROCK2 in airway smooth muscle contraction. Our results demonstrate that ozone-induced AHR requires ROCK. Whereas ROCK1-dependent changes in hyaluronan may contribute to ROCK1's role in O3-induced AHR, the role of ROCK2 is downstream of inflammation, likely at the level of airway smooth muscle contraction.

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Lu, Weizhuo, Jiyue Wen, and Zhiwu Chen. "Distinct Roles of ROCK1 and ROCK2 on the Cerebral Ischemia Injury and Subsequently Neurodegenerative Changes." Pharmacology 105, no. 1-2 (September 19, 2019): 3–8. http://dx.doi.org/10.1159/000502914.

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Cerebral ischemic injury is one of the main causes of adult disability and death. Although significant progress has been made, cerebral ischemia continues to be a major risk to public health worldwide. The Rho kinase (ROCK) signaling pathway has been reported to be significantly involved in many mechanisms of cerebral injury. Although ROCK is ubiquitously expressed in all tissues, ROCK2 subtype expression in brain and the spinal cord is more abundant and improves with age. This makes it a promising target for new therapeutic approaches. In this article, we review the current knowledge on the involvement of ROCK in cerebral ischemia injury and neurodegenerative changes after cerebral injury. After a detailed description of the mechanism of ROCK involvement in axonal regeneration and synaptic function, different roles of ROCK1 and ROCK2 in neurons under physiological and pathological conditions are compared and discussed. In addition, different functions of genetic and pharmacological inhibitions of ROCK1 and ROCK2 on cerebral injury are discussed.

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Couzens, Amber L., Vivian Saridakis, and Michael P. Scheid. "The hydrophobic motif of ROCK2 requires association with the N-terminal extension for kinase activity." Biochemical Journal 419, no. 1 (March 13, 2009): 141–48. http://dx.doi.org/10.1042/bj20081376.

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ROCK (Rho-associated coiled-coil kinase) 2 is a member of the AGC kinase family that plays an essential role downstream of Rho in actin cytoskeleton assembly and contractility. The process of ROCK2 activation is complex and requires suppression of an autoinhibitory mechanism that is facilitated by Rho binding. ROCK2 harbours a C-terminal extension within the kinase domain that contains a hydrophobic cluster of phenylalanine and tyrosine residues surrounding a key threonine residue. In growth-factor-stimulated AGC kinases, the hydrophobic motif is important for the transition of the kinase from inactive to active complex and requires phosphorylation of the conserved serine/threonine residue. Less is understood about the contribution that the hydrophobic motif plays in the activation of ROCK, and the role of the hydrophobic motif threonine at position 405. In the present study, we show that this residue of ROCK is essential for substrate phosphorylation and kinase domain dimerization. However, in contrast with the growth-factor-activated AGC kinases, a phosphomimetic residue at position 405 was inhibitory for ROCK2 activity and dimerization. A soluble hydrophobic motif peptide allosterically activated ROCK2 In vitro, but not the equivalent peptide with Asp405 substitution. Mechanistically, both ROCK2 activity and dimerization were dependent upon the interaction between Thr405 of the hydrophobic motif and Asp39 of the N-terminal extension. The reciprocal exchange of these residues was permissive for kinase activity, but dimerization was lost. These results support the rationale for development of small-molecule inhibitors designed to block ROCK activation by selectively interfering with hydrophobic motif-mediated activation-state transition and dimer formation.

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Pelosi, Michele, Francesco Marampon, Bianca M. Zani, Sabrina Prudente, Emerald Perlas, Viviana Caputo, Luciano Cianetti, et al. "ROCK2 and Its Alternatively Spliced Isoform ROCK2m Positively Control the Maturation of the Myogenic Program." Molecular and Cellular Biology 27, no. 17 (July 2, 2007): 6163–76. http://dx.doi.org/10.1128/mcb.01735-06.

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ABSTRACT Signal transduction cascades involving Rho-associated kinases (ROCK), the serine/threonine kinases downstream effectors of Rho, have been implicated in the regulation of diverse cellular functions including cytoskeletal organization, cell size control, modulation of gene expression, differentiation, and transformation. Here we show that ROCK2, the predominant ROCK isoform in skeletal muscle, is progressively up-regulated during mouse myoblast differentiation and is highly expressed in the dermomyotome and muscle precursor cells of mouse embryos. We identify a novel and evolutionarily conserved ROCK2 splicing variant, ROCK2m, that is preferentially expressed in skeletal muscle and strongly up-regulated during in vivo and in vitro differentiation processes. The specific knockdown of ROCK2 or ROCK2m expression in C2C12 myogenic cells caused a significant and selective impairment of the expression of desmin and of the myogenic regulatory factors Mrf4 and MyoD. We demonstrate that in myogenic cells, ROCK2 and ROCK2m are positive regulators of the p42 and p44 mitogen-activated protein kinase-p90 ribosomal S6 kinase-eucaryotic elongation factor 2 intracellular signaling pathways and, thereby, positively regulate the hypertrophic effect elicited by insulin-like growth factor 1 and insulin, linking the multifactorial functions of ROCK to an important control of the myogenic maturation.

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Zhang, Ying, Linpei Jia, Wei Ji, and Hai Li. "MicroRNA-141 Inhibits the Proliferation of Penile Cavernous Smooth Muscle Cells Associated with Down-Regulation of the Rhoa/Rho Kinase Signaling Pathway." Cellular Physiology and Biochemistry 48, no. 1 (2018): 348–60. http://dx.doi.org/10.1159/000491741.

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Background/Aims: The role of the RhoA/Rho kinase signaling pathway in diabetes mellitus-induced erectile dysfunction has been partially understood. Methods: In the present study, we explored the changes of the RhoA/Rho associated kinase (ROCK) signaling pathway in diabetic erectile dysfunction in vivo and the effects of microRNA-141 on the RhoA/ROCK signaling pathway in vitro. Results: The mRNA and protein expressions of RhoA and ROCK2 were significantly increased while the expression of microRNA-141 was decreased in the penile cavernous smooth muscle cells of rats with diabetic erectile dysfunction. Moreover, increased expression of microRNA-141, decreased expressions of RhoA and ROCK2 (mRNA and protein), accelerated cell proliferation rate and reduced cell apoptosis were found in the microRNA-141 mimics group and the siRNA-Rho group. The microRNA-141 expression in the microRNA-141 inhibitors + siRNA-Rho group was significantly decreased. microRNA-141 specifically bound to Rho-3’-UTR and down-regulated the expression of Rho gene at the post transcriptional level. Conclusion: Decreased expression of miR-141 is associated with up-regulation of RhoA and ROCK2 in the RhoA/ROCK signaling pathway in rats with diabetic erectile dysfunction. miR-141 inhibits the growth of penile cavernous smooth muscle cells associated with down-regulation of the RhoA/ROCK signaling pathway in vitro.

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Cheng, Chao, Xiao-Bo Liu, Dong-Ling Xu, and Juan Zhang. "Increased ROCK1 not ROCK2 in circulating leukocytes in rats with myocardial ischemia/reperfusion." Perfusion 35, no. 8 (April 20, 2020): 819–25. http://dx.doi.org/10.1177/0267659120915140.

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Background: Rho-associated protein kinase (ROCK) plays a vital role in the pathogenesis of many cardiovascular diseases. Previous studies have demonstrated that ROCK is overactivated and involved in myocardial ischemia/reperfusion in vivo. But the role of ROCK in circulating leukocytes during myocardial ischemia/reperfusion is not well studied. Material and methods: This study was performed to evaluate ROCK activity in circulating leukocytes in rats with myocardial ischemia/reperfusion injury. Myocardial ischemia/reperfusion Wistar rats were subjected to 30-min ischemia followed by 180-min reperfusion. ROCK activity in circulating leukocytes was examined by the phosphorylation state of myosin phosphatase targeting subunit 1, a substrate of ROCK. Results: ROCK activity significantly increased in leukocytes in rat ischemia/reperfusion models compared to the sham group. ROCK1 not ROCK2 level in circulating leukocytes was significantly elevated in ischemia/reperfusion. Administration of the selective inhibitor of ROCK, fasudil, significantly reduced myocardial infarct size, myocyte apoptosis, and inflammatory cytokine, including interleukin 6 and tumor necrosis factor α. Furthermore, fasudil upregulated ischemia/reperfusion-induced reduction of nitric oxide production. Conclusion: Increased ROCK1 not ROCK2 in circulating leukocytes plays a role in the pathogenesis of myocardial ischemia/reperfusion injury. Inhibition of ROCK1 in circulating leukocytes has an important role in fasudil-induced cardioprotective effects. ROCK1 in circulating leukocytes might be a new biomarker in myocardial ischemia/reperfusion injury.

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Kicka, Sebastian, Zhouxin Shen, Sarah J. Annesley, Paul R. Fisher, Susan Lee, Steven Briggs, and Richard A. Firtel. "The LRRK2-related Roco kinase Roco2 is regulated by Rab1A and controls the actin cytoskeleton." Molecular Biology of the Cell 22, no. 13 (July 2011): 2198–211. http://dx.doi.org/10.1091/mbc.e10-12-0937.

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We identify a new pathway that is required for proper pseudopod formation. We show that Roco2, a leucine-rich repeat kinase 2 (LRRK2)-related Roco kinase, is activated in response to chemoattractant stimulation and helps mediate cell polarization and chemotaxis by regulating cortical F-actin polymerization and pseudopod extension in a pathway that requires Rab1A. We found that Roco2 binds the small GTPase Rab1A as well as the F-actin cross-linking protein filamin (actin-binding protein 120, abp120) in vivo. We show that active Rab1A (Rab1A-GTP) is required for and regulates Roco2 kinase activity in vivo and that filamin lies downstream from Roco2 and controls pseudopod extension during chemotaxis and random cell motility. Therefore our study uncovered a new signaling pathway that involves Rab1A and controls the actin cytoskeleton and pseudopod extension, and thereby, cell polarity and motility. These findings also may have implications in the regulation of other Roco kinases, including possibly LRRK2, in metazoans.

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Noma, Kensuke, Naotsugu Oyama, and James K. Liao. "Physiological role of ROCKs in the cardiovascular system." American Journal of Physiology-Cell Physiology 290, no. 3 (March 2006): C661—C668. http://dx.doi.org/10.1152/ajpcell.00459.2005.

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Rho-associated kinases (ROCKs), the immediate downstream targets of RhoA, are ubiquitously expressed serine-threonine protein kinases that are involved in diverse cellular functions, including smooth muscle contraction, actin cytoskeleton organization, cell adhesion and motility, and gene expression. Recent studies have shown that ROCKs may play a pivotal role in cardiovascular diseases such as vasospastic angina, ischemic stroke, and heart failure. Indeed, inhibition of ROCKs by statins or other selective inhibitors leads to the upregulation and activation of endothelial nitric oxide synthase (eNOS) and reduction of vascular inflammation and atherosclerosis. Thus inhibition of ROCKs may contribute to some of the cholesterol-independent beneficial effects of statin therapy. Currently, two ROCK isoforms have been identified, ROCK1 and ROCK2. Because ROCK inhibitors are nonselective with respect to ROCK1 and ROCK2 and also, in some cases, may be nonspecific with respect to other ROCK-related kinases such as myristolated alanine-rich C kinase substrate (MARCKS), protein kinase A, and protein kinase C, the precise role of ROCKs in cardiovascular disease remains unknown. However, with the recent development of ROCK1- and ROCK2-knockout mice, further dissection of ROCK signaling pathways is now possible. Herein we review what is known about the physiological role of ROCKs in the cardiovascular system and speculate about how inhibition of ROCKs could provide cardiovascular benefits.

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Jiang, Caixia, Wei Gong, Rong Chen, Huihui Ke, Xiaoyan Qu, Weihong Yang, and Zhongping Cheng. "RhoA/ROCK/ARHGAP26 signaling in the eutopic and ectopic endometrium is involved in clinical characteristics of adenomyosis." Journal of International Medical Research 46, no. 12 (November 2, 2018): 5019–29. http://dx.doi.org/10.1177/0300060518789038.

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Objective This study aimed to investigate RhoA, RhoA-associated coiled-coil containing protein kinase (ROCK) 1, ROCK2, and Rho GTPase-activating protein 26 (ARHGAP26) expression in the eutopic endometrium (EU) and ectopic endometrium (EC), and examine their relationships with the clinical characteristics of adenomyosis. Methods Twenty patients with adenomyosis who underwent laparoscopy were recruited. Protein and mRNA expression of RhoA, ROCK1, ROCK2, and ARHGAP26 in EU and EC of patients with adenomyosis and in control endometrium without adenomyosis (CE) was detected. Results ROCK1, ROCK2, and RhoA mRNA expression in EU was significantly higher than that in CE, and was highest in EC. ARHGAP26 mRNA expression in EC and EU was significantly lower than that in CE. ROCK1, ROCK2, and RhoA protein expression in EC and EU was significantly higher than that in CE. ARHGAP26 protein expression in EC and EU was significantly lower than that in CE. ROCK1, ROCK2, and RhoA gene and protein expression was positively associated and ARHGAP26 was negatively associated with the severity of menorrhagia and menstrual capacity in adenomyosis. Conclusions RhoA, ROCK1, and ROCK2 expression is upregulated, and ARHGAP26 expression is downregulated in adenomyosis. The RhoA/ROCK-mediated signaling pathway is associated with dysmenorrhea and menstrual capacity in adenomyosis.

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Huang, Lei, Fan Dai, Lian Tang, Xiaofeng Bao, Zhaoguo Liu, Chao Huang, Ting Zhang, and Wenjuan Yao. "Distinct Roles For ROCK1 and ROCK2 in the Regulation of Oxldl-Mediated Endothelial Dysfunction." Cellular Physiology and Biochemistry 49, no. 2 (2018): 565–77. http://dx.doi.org/10.1159/000492994.

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Background/Aims: This study used Rho-associated protein kinase (ROCK) isoform-selective suppression or a ROCK inhibitor to analyze the roles of ROCK1 and ROCK2 in regulating endothelial dysfunction triggered by oxidized low-density lipoprotein (oxLDL). Methods: ROCK1 or ROCK2 expression in human umbilical vein endothelial cells (HUVECs) was suppressed by small interfering RNA (siRNA). HUVECs were pretreated with 30 μM Y27632 (pan ROCK inhibitor) for 30 min before exposure to 200 μg/mL oxLDL for an additional 24 h. Cell viability was determined by the MTT assay, and cell apoptosis was evaluated by the TUNEL assay. Protein expression and phosphorylation were assessed by Western blot analysis. The morphology of total and phosphorylated vimentin (p-vimentin) and the co-localization of vimentin with vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) were detected by the immunofluorescence assay. The adhesion of promonocytic U937 cells to HUVECs was observed by light microscopy. Results: ROCK2 suppression or Y27632 treatment, rather than ROCK1 deletion, effectively reduced endothelial cell apoptosis and preserved cell survival. ROCK2 suppression exhibited improved vimentin and p-vimentin cytoskeleton stability and decreased vimentin cleavage by attenuating caspase-3 activity. In addition, increased p-vimentin expression induced by oxLDL was significantly inhibited by ROCK2 deletion or Y27632 treatment. In contrast, ROCK1 suppression showed no obvious effects on the vimentin cytoskeleton, but significantly regulated the expression of adhesion molecules. Endothelial ICAM-1 or VCAM-1 expression induced by oxLDL was obviously inhibited by ROCK1 suppression or Y27632 treatment. Moreover, the expression of ICAM-1 induced by oxLDL could also be reduced by ROCK2 suppression. Furthermore, ROCK2 deficiency or Y27632 treatment inhibited the redistribution of adhesion molecules and their co-localization with vimentin caused by oxLDL. These effects resulted in the significant inhibition of monocyte-endothelial adhesion induced by oxLDL. Conclusion: The results of this study support the novel concept that ROCK1 is involved in oxLDL-induced cell adhesion by regulating adhesion molecule expression, whereas ROCK2 is required for both endothelial apoptosis and adhesion by regulating both the vimentin cytoskeleton and adhesion molecules. Consequently, ROCK1 and ROCK2 have distinct roles in the regulation of oxLDL-mediated endothelial dysfunction.

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Rozo, Cristina, Yurii Chinenov, Reena Khianey Maharaj, Sanjay Gupta, Laura Leuenberger, Kyriakos A. Kirou, Vivian P. Bykerk, Susan M. Goodman, Jane E. Salmon, and Alessandra B. Pernis. "Targeting the RhoA-ROCK pathway to reverse T-cell dysfunction in SLE." Annals of the Rheumatic Diseases 76, no. 4 (November 9, 2016): 740–47. http://dx.doi.org/10.1136/annrheumdis-2016-209850.

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ObjectivesDeregulated production of interleukin (IL)-17 and IL-21 contributes to the pathogenesis of autoimmune disorders such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Production of IL-17 and IL-21 can be regulated by ROCK2, one of the two Rho kinases. Increased ROCK activation was previously observed in an SLE cohort. Here, we evaluated ROCK activity in a new SLE cohort, and an RA cohort, and assessed the ability of distinct inhibitors of the ROCK pathway to suppress production of IL-17 and IL-21 by SLE T cells or human Th17 cells.MethodsROCK activity in peripheral blood mononuclear cells (PBMCs) from 29 patients with SLE, 31 patients with RA and 28 healthy controls was determined by ELISA. SLE T cells or in vitro-differentiated Th17 cells were treated with Y27632 (a pan-ROCK inhibitor), KD025 (a selective ROCK2 inhibitor) or simvastatin (which inhibits RhoA, a major ROCK activator). ROCK activity and IL-17 and IL-21 production were assessed. The transcriptional profile altered by ROCK inhibitors was evaluated by NanoString technology.ResultsROCK activity levels were significantly higher in patients with SLE and RA than healthy controls. Th17 cells exhibited high ROCK activity that was inhibited by Y27632, KD025 or simvastatin; each also decreased IL-17 and IL-21 production by purified SLE T cells or Th17 cells. Immune profiling revealed both overlapping and distinct effects of the different ROCK inhibitors.ConclusionsROCK activity is elevated in PBMCs from patients with SLE and RA. Production of IL-17 and IL-21 by SLE T cells or Th17 cells can furthermore be inhibited by targeting the RhoA-ROCK pathway via both non-selective and selective approaches.

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Les, Francisco, Guillermo Cásedas, Marta Sofía Valero, José Miguel Arbonés-Mainar, and Víctor López. "Rock tea (Jasonia glutinosa (L.) DC.) polyphenolic extract inhibits triglyceride accumulation in 3T3-L1 adipocyte-like cells and obesity related enzymes in vitro." Food & Function 11, no. 10 (2020): 8931–38. http://dx.doi.org/10.1039/d0fo01497d.

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Kim, Yong-Woo, Eunoo Bak, Seoyoung Wy, Seung-Chan Lee, Yu-Jeong Kim, Young-Kook Kim, Ki-Ho Park, and Jin-Wook Jeoung. "Genetic Risk and Phenotype Correlation of Primary Open-Angle Glaucoma Based on Rho-Kinase Gene Polymorphisms." Journal of Clinical Medicine 10, no. 9 (May 1, 2021): 1953. http://dx.doi.org/10.3390/jcm10091953.

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Rho-associated coiled-coil kinase (ROCK) signaling can affect glaucoma risk by regulating trabecular meshwork outflow. We investigated the effect of ROCK gene polymorphism on the risks of primary open-angle glaucoma (POAG) and POAG-related phenotypes including intraocular pressure (IOP) in a Korean population. A total of 24 single-nucleotide polymorphisms (SNPs) from ROCK1 and ROCK2 were selected and genotyped for 363 POAG patients and 213 healthy controls. Among the 363 POAG patients, 282 were normal-tension glaucoma (NTG, baseline IOP ≤ 21 mmHg) and 81 were high-tension glaucoma (HTG, baseline IOP > 21 mmHg). The SNPs rs288979, rs1006881, rs35996865, rs10083915, and rs11873284 in ROCK1 (tagged to each other, r2 = 1) were nominally associated with risk of HTG (OR = 0.52, p = 0.045). However, there were no SNPs that were significantly associated with the risk of NTG. In the genotype-phenotype correlation analysis, the SNPs rs2230773 and rs3771106 in ROCK2 were significantly correlated with central corneal thickness (CCT)-adjusted IOP (p = 0.024) and axial length (AXL; p = 0.024), respectively. The present data implicated the role of ROCK in POAG development, and as such, can serve as a good reference for upcoming Rho/ROCK-pathway-related studies on POAG.

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Fereidooni, Davood, Gholam Reza Khanlari, and Mojtaba Heidari. "Assessment of a Modified Rock Mass Classification System for Rock Slope Stability Analysis in the Q-system." Earth Sciences Research Journal 19, no. 2 (December 17, 2015): 147–52. http://dx.doi.org/10.15446/esrj.v19n2.49127.

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This paper explores the applicability of a modified Q classification system and its component parameters for analysis and conclusion of site investigation data to estimate rock slope stability. Based on the literature, Q classification system has high applicable potential for evaluation of rock mass quality. Therefore, in this study, it was used with RMR and SMR rock mass classification systems to assess stability or instability of different rock slopes along the Hamedan-Ganjnameh-Tuyserkan road, Hamedan province west of Iran. Furthermore, a modified rock mass classification system namely Slope Quality Rating (SQR) was proposed based on the correction of the Q classification parameters and calculating some new parameters such as dip and strike of discontinuities and the method of rock excavation or blasting. For this purpose, the SMR and RMR rock mass classifications were also needed. By measuring SQR for different rock slopes, it will be possible to measure Slope Mass Rating (SMR). Evaluación del sistema Q modificado de clasificación del macizo rocoso para el análisis de estabilidad de pendiente de roca ResumenEste artículo explora la aplicabilidad del sistema de clasificación Q modificado y sus parámetros para analizar y determinar la información estimada de estabilidad de pendiente de roca en el sitio determinado de estudio. Según la literatura, el sistema de clasificación Q tiene un alto potencial de aplicabilidad paral a evaluación de la calidad del macizo rocoso. En este estudio además se utilizó el sistema Q junto con los sistemas Índice de Masa de Pendiente (SMR) y Clasificación Geomecánica de Bienawski (RMR) para evaluar la estabilidad e inestabilidad de diferentes pendientes rocosas en la carretera Hamedan-Ganjnameh-Tuyserkan, de la provincia de Hamedan, en el Oeste de Irán. Además, se propone el Índice de Calidad de Pendiente (SQR), un sistema de clasificación de macizo rocoso modificado, a partir de la corrección de los parámetros de clasificación Q y el cálculo de nuevos parámetros como pendiente y caída de las discontinuidades y el método de excavación o explosión de la roca. Para esta propuesta también se utilizaron las clasificaciones SMR y RMR. La medición SQR en diferentes pendientes hizo posible el cálculo del sistema SMR.

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Lambert, James A., and Weifeng Song. "Ozone-induced airway hyperresponsiveness: roles of ROCK isoforms." American Journal of Physiology-Lung Cellular and Molecular Physiology 309, no. 12 (December 15, 2015): L1394—L1397. http://dx.doi.org/10.1152/ajplung.00353.2015.

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Acute ozone (O3) inhalation has been shown to cause airway and pulmonary epithelial injury with accompanying inflammation responses. Robust evidence exists that O3 induces airway hyperresponsiveness (AHR) in humans and in animal models. Several pathways exist that culminate in airway smooth muscle contraction, but the mechanism(s) by which O3 elicits AHR are unclear. Here, we review the recent report by Kasahara et al. (Kasahara DI, Mathews JA, Park CY, Cho Y, Hunt G, Wurmbrand AP, Liao JK, Shore SA. Am J Physiol Lung Cell Mol Physiol 309: L736–L746, 2015.) describing the role of two Rho kinase (ROCK) isoforms in O3-induced AHR utilizing a murine haploinsufficiency model. Compared with wild-type (WT) mice, the authors report that ROCK1+/− and ROCK2+/− mice exhibited significantly reduced AHR following acute exposure to O3. Additionally, WT mice treated with fasudil, an FDA-approved ROCK1/2 inhibitor, recapitulated reduction in AHR as seen in ROCK haplotypes. It was suggested that, although the two ROCK isoforms are both induced by Rho, they have different mechanisms by which they mediate O3-induced AHR: ROCK1 via hyaluronan signaling vs. ROCK2 acting downstream of inflammation at the level of airway smooth muscle contraction. These observations provide an important framework to develop novel ROCK-targeting therapies for acute O3-induced AHR.

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Röchert, Daniel, German Neubaum, Björn Ross, Florian Brachten, and Stefan Stieglitz. "Opinion-based Homogeneity on YouTube : Combining Sentiment and Social Network Analysis." Computational Communication Research 2, no. 1 (February 1, 2020): 81–108. http://dx.doi.org/10.5117/ccr2020.1.004.roch.

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Abstract When addressing public concerns such as the existence of politically like-minded communication spaces in social media, analyses of complex political discourses are met with increasing methodological challenges to process communication data properly. To address the extent of political like-mindedness in online communication, we argue that it is necessary to focus not only on ideological homogeneity in online environments, but also on the extent to which specific political questions are discussed in a uniform manner. This study proposes an innovative combination of computational methods, including natural language processing and social network analysis, that serves as a model for future research examining the evolution of opinion climates in online networks. Data were gathered on YouTube, enabling the assessment of users’ expressed opinions on three political issues (i.e., adoption rights for same-sex couples, headscarf rights, and climate change). Challenging widely held assumptions on discursive homogeneity online, the results provide evidence for a moderate level of connections between dissimilar YouTube comments but few connections between agreeing comments. The findings are discussed in light of current computational communication research and the vigorous debate on the prevalence of like-mindedness in online networks.

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Åkervall, Lisa. "McMansion of media excess: Ryan Trecartin’s and Lizzie Fitch’s SITE VISIT." NECSUS. European Journal of Media Studies 4, no. 1 (January 1, 2015): 279–86. http://dx.doi.org/10.5117/necsus2015.1.ros2.

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Rock, Jan. "Boekbespreking - Liselotte Vandenbussche, Het veld der verbeelding. Vrijzinnige vrouwen in Vlaamse literaire en algemeen-culturele tijdschriften (1870- 1914). Studies op het gebied van de moderne Nederlandse literatuur, 13 / Christophe Verbruggen, Schrijverschap in de Belgische belle époque. Een sociaal-culturele geschiedenis." Tijdschrift voor Geschiedenis 126, no. 1 (March 1, 2013): 141–43. http://dx.doi.org/10.5117/tvgesch2013.1.rock.

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Li, Chunling, Fei Sun, Hoonsik Cho, Vamshi Yelavarthi, Changmo Sohn, Chuan He, Olaf Schneewind, and Taeok Bae. "CcpA Mediates Proline Auxotrophy and Is Required for Staphylococcus aureus Pathogenesis." Journal of Bacteriology 192, no. 15 (June 2, 2010): 3883–92. http://dx.doi.org/10.1128/jb.00237-10.

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ABSTRACT Human clinical isolates of Staphylococcus aureus, for example, strains Newman and N315, cannot grow in the absence of proline, albeit their sequenced genomes harbor genes for two redundant proline synthesis pathways. We show here that under selective pressure, S. aureus Newman generates proline-prototrophic variants at a frequency of 3 × 10−6, introducing frameshift and missense mutations in ccpA or IS1811 insertions in ptsH, two regulatory genes that carry out carbon catabolite repression (CCR) in staphylococci and other Gram-positive bacteria. S. aureus Newman variants with mutations in rocF (arginase), rocD (ornithine aminotransferase), and proC (Δ1-pyrroline 5-carboxylate [P5C] reductase) are unable to generate proline-prototrophic variants, whereas a variant with a mutation in ocd (ornithine cyclodeaminase) is unaffected. Transposon insertion in ccpA also restored proline prototrophy. CcpA was shown to repress transcription of rocF and rocD, encoding the first two enzymes, but not of proC, encoding the third and final enzyme in the P5C reductase pathway. CcpA bound to the upstream regions of rocF and rocD but not to that of proC. CcpA's binding to the upstream regions was greatly enhanced by phosphorylated HPr. The CCR-mediated proline auxotrophy was lifted when nonpreferred carbohydrates were used as the sole carbon source. The ccpA mutant displayed reduced staphylococcal load and replication in a murine model of staphylococcal abscess formation, indicating that carbon catabolite repression presents an important pathogenesis strategy of S. aureus infections.

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Aburima, Ahmed, Katie S. Wraith, Zaher Raslan, Robert Law, Simbarashe Magwenzi, and Khalid M. Naseem. "cAMP signaling regulates platelet myosin light chain (MLC) phosphorylation and shape change through targeting the RhoA-Rho kinase-MLC phosphatase signaling pathway." Blood 122, no. 20 (November 14, 2013): 3533–45. http://dx.doi.org/10.1182/blood-2013-03-487850.

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Key Points Protein kinase A (PKA) phosphorylates RhoA on serine188 to inhibit RhoA membrane translocation and RhoA kinase (ROCK) signaling. Inhibition of RhoA/ROCK2 promotes myosin light chain (MLC) phosphatase activity, which prevents the phosphorylation of MLC and platelet shape change.

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Kang, Yun Hwan, and Heung Mook Shin. "Vasorelaxant Effect of Cinnamomi Ramulus Ethanol Extract via Rho-Kinase Signaling Pathway." American Journal of Chinese Medicine 39, no. 05 (January 2011): 867–78. http://dx.doi.org/10.1142/s0192415x11009263.

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The Rho-kinase (ROCK) signaling pathway is substantially involved in vascular contraction. This study investigated the vasodilatory effects and possible mechanisms of Cinnamomi ramulus ethanol extract (CRE), with the hypothesis that the CRE vasodilatory effect involves RhoA and the ROCK signaling pathway in rat aortic preparations. CRE (0.05–1 mg/ml) dose-dependently relaxed the vascular contraction induced by phenylephrine and calpeptin in an endothelium-independent manner. Measurement of the expression levels of ROCK-related signaling molecules in response to calpeptin revealed that CRE completely inhibited RhoA and ROCK2 protein expressions. Furthermore, CRE dephosphorylated the subsequent downstream targets myosin phosphatase targeting subunit 1 (MYPT-1), protein kinase C potentiated phosphatase inhibitor protein-17 kDa (CPI-17) and myosin light chain 20 kDa (MLC20). We conclude that the vasorelaxation effect of CRE occurs via downregulation of ROCK signal molecules.

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Ebata, Takahiro, Yasumasa Mitsui, Wataru Sugimoto, Miho Maeda, Keigo Araki, Hiroaki Machiyama, Ichiro Harada, et al. "Substrate Stiffness Influences Doxorubicin-Induced p53 Activation via ROCK2 Expression." BioMed Research International 2017 (2017): 1–10. http://dx.doi.org/10.1155/2017/5158961.

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The physical properties of the extracellular matrix (ECM), such as stiffness, are involved in the determination of the characteristics of cancer cells, including chemotherapy sensitivity. Resistance to chemotherapy is often linked to dysfunction of tumor suppressor p53; however, it remains elusive whether the ECM microenvironment interferes with p53 activation in cancer cells. Here, we show that, in MCF-7 breast cancer cells, extracellular stiffness influences p53 activation induced by the antitumor drug doxorubicin. Cell growth inhibition by doxorubicin was increased in response to ECM rigidity in a p53-dependent manner. The expression of Rho-associated coiled coil-containing protein kinase (ROCK) 2, which induces the activation of myosin II, was significantly higher when cells were cultured on stiffer ECM substrates. Knockdown of ROCK2 expression or pharmacological inhibition of ROCK decreased doxorubicin-induced p53 activation. Our results suggest that a soft ECM causes downregulation of ROCK2 expression, which drives resistance to chemotherapy by repressing p53 activation.

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Newell-Litwa, Karen A., Mathilde Badoual, Hannelore Asmussen, Heather Patel, Leanna Whitmore, and Alan Rick Horwitz. "ROCK1 and 2 differentially regulate actomyosin organization to drive cell and synaptic polarity." Journal of Cell Biology 210, no. 2 (July 13, 2015): 225–42. http://dx.doi.org/10.1083/jcb.201504046.

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RhoGTPases organize the actin cytoskeleton to generate diverse polarities, from front–back polarity in migrating cells to dendritic spine morphology in neurons. For example, RhoA through its effector kinase, RhoA kinase (ROCK), activates myosin II to form actomyosin filament bundles and large adhesions that locally inhibit and thereby polarize Rac1-driven actin polymerization to the protrusions of migratory fibroblasts and the head of dendritic spines. We have found that the two ROCK isoforms, ROCK1 and ROCK2, differentially regulate distinct molecular pathways downstream of RhoA, and their coordinated activities drive polarity in both cell migration and synapse formation. In particular, ROCK1 forms the stable actomyosin filament bundles that initiate front–back and dendritic spine polarity. In contrast, ROCK2 regulates contractile force and Rac1 activity at the leading edge of migratory cells and the spine head of neurons; it also specifically regulates cofilin-mediated actin remodeling that underlies the maturation of adhesions and the postsynaptic density of dendritic spines.

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Gárate -Lizárraga, I., B. Pérez -Cruz, J. A. Díaz -Ortíz, M. A. Alarcón -Tacuba, M. A. Alarcón -Romero, L. A. Chávez -Almazán, J. L. García -Barbosa, and E. Diego -Valderrama. "BLOOMS OF Pyrodinium bahamense var. compressum AND ROCK OYSTER TOXICITY IN COSTA CHICA, GUERRERO, MEXICO." CICIMAR Oceánides 28, no. 1 (June 30, 2013): 37. http://dx.doi.org/10.37543/oceanides.v28i1.122.

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Blooms of Pyrodinium bahamense var. compressum were detected from July to December 2010 in Costa Chica, Guerrero. To estimate the cell abundance of this dinoflagellate, phytoplankton samples were collected from 7 July to 9 December 2010 at five sampling sites. Wild rock oysters and specimens from fishing cooperatives were only collected during November-December 2010. Abundance of P. bahamense var. compressum ranged from < 1000 to 194000 cells L–1 in the first three samplings performed in July. Low densities (< 9000 cells L–1) were observed at the end of November and December. Rock oyster toxicity from the fishing areas ranged from 46.24 to 788.85 μg STXeq 100 g–1. Rock oyster samples collected in the fishing cooperatives had toxicity from 52.2 to 440.88 μg STXeq 100 g–1. Although rock oysters were collected at the end of the blooms, their toxicity could be associated to this dinoflagellate both during this period and during previous blooms that occurred from on July-August in the study area. Florecimientos de Pyrodinium bahamense var. compressum y toxicidad en ostión de roca en Costa Chica, Guerrero, México Se detectaron florecimientos de Pyrodinium bahamense var. compressum de julio a diciembre de 2010 en Costa Chica, Guerrero. Con el fin de calcular la abundancia de este dinoflagelado se recolectaron muestras de fitoplancton desde el 7 de Julio hasta el 9 de diciembre en cinco estaciones de muestreo. Asimismo, se recolectó ostión de roca en los sitios naturales de captura y en cooperativas pesqueras de la región de noviembre a diciembre. La abundancia de P. bahamense var. compressum alcanzó valores < 1000 y máximos 194000 céls L–1 en los tres primeros muestreos realizados en julio; se observaron bajas densidades (< 9000 cells L–1) a finales de noviembre y diciembre. La toxicidad del ostión de roca recolectado en los sitios de captura comercial varió entre 46.24 y 788.85 μg STXeq 100 g–1. La toxicidad en las muestras de ostión recolectado en las cooperativas pesqueras varió entre 52.2 y 440.88 μg STXeq 100 g–1. Aunque el ostión de roca fue recolectado al final de los florecimientos, su toxicidad puede asociarse a la presencia del dinoflagelado, tanto en estas fechas como por los florecimientos previos ocurridos entre julio-agosto en el área de estudio.

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MAKAROV, V. V. "METHODOLOGICAL PRINCIPALSOF GEOMECHANICS OF HIGHLY COMPRESSED ROCK AND ROCK MASSIFS." Mining Informational and analytical bulletin 12, no. 62 (2018): 5–10. http://dx.doi.org/10.25018/0236-1493-2018-12-62-5-10.

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Rocchietti, Ana Maria. "TRES SITIOS RUPESTRES EN LA SIERRA DE COMECHINGONES, PROVINCIA DE CÓRDOBA / Three rock art sites in Comechingones Hill, Cordoba Province." Revista del Museo de Antropología 9, no. 1 (June 22, 2016): 21. http://dx.doi.org/10.31048/1852.4826.v9.n1.11257.

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Resumen Este artículo presenta tres sitios rupestres que considera “transversales” en su enigmático contenido pictográfico y propone su análisis con la perspectiva de que exigió una imaginación alucinada y que supuso una ideología dotada de una coherencia similar. Este arte se encuentra en la Sierra de Comechingones, Provincia de Córdoba. En las tres obras parece existir alienación en el lenguaje gráfico, un experimento en el despliegue de la pintura y una energía psíquica común. Las geoformas que las contienen posee un alto impacto visual y permiten inferir que arte y roca forman un conjunto sígnico inseparable. La roca –en tanto significante- precede al arte y realiza un “corte” en lo real de tal modo que predetermina la significación. Esto hace singular a cualquier sitio rupestre. Las rocas definieron Abstract This paper presents three rock art sites, considers it “transversal” in their enigmatic pictorial content, offers an analysis with the perspective that it demanded a hallucinated imagination and that was an ideology of a similar consistency. This art is located in the Sierra de Comechingones, Province of Cordoba. It seems to be alienation in graphic language, an experiment in painting and deployment of a common psychic energy. Geoforms containing them have a high visual impact; art and rock form a simbolic whole. The rock is a signifier and precedes the art; it performs a “cut” about real in such a way that it predetermines the significance. Therefore, any rock site is unique. Rocks defined the charm of the place of rock art before this existed.

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Arndt, Petra, Christopher Volk, Valentin Gorboulev, Thomas Budiman, Christian Popp, Isabel Ulzheimer-Teuber, Aida Akhoundova, et al. "Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1." American Journal of Physiology-Renal Physiology 281, no. 3 (September 1, 2001): F454—F468. http://dx.doi.org/10.1152/ajprenal.2001.281.3.f454.

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The rat organic cation transporter (rOCT)-2 was characterized by electrical and tracer flux measurements compared with rOCT1. By applying choline gradients to voltage-clamped Xenopus oocytes expressing rOCT2, potential-dependent currents could be induced in both directions. Tracer flux measurements with seven organic cations revealed similar Michaelis-Menten constant values for both transporters, with the exception of guanidine. In parallel experiments with rOCT2 and rOCT1, inhibition of tetraethylammonium transport by 12 cations, 2 weak bases, corticosterone, and the anions para-amminohippurate, α-ketoglutarate, and probenecid was characterized. The IC50values of many inhibitors were similar for both transporters, whereas others were significantly different. Mepiperphenidol and O-methylisoprenaline showed an ∼70-fold lower and corticosterone a 38-fold higher affinity for rOCT2. With the use of these inhibitors together with previous information on cation transporters, experimental protocols are proposed to dissect out the individual contributions of rOCT2 and rOCT1 in intact proximal tubule preparations. Inhibition experiments at different pH levels strongly suggest that the weak base quinine passively permeates the plasma membrane at physiological pH and inhibits rOCT2 from the intracellular side.

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Le Mare, P. H. "Rock Phosphates in Agriculture." Experimental Agriculture 27, no. 4 (October 1991): 413–22. http://dx.doi.org/10.1017/s0014479700019396.

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SUMMARYThe principles that control effectiveness of rock phosphates as fertilizer are now fairly well understood so that the potential effect of a material can be predicted with some confidence from laboratory analysis of the raw material. Soil characteristics, especially acidity, and calcium and phosphate status, are important: if these are not conducive to dissolution, crop response to rock phosphate is small. Some crop characteristics, especially the extent of root systems and whether they are infected with mycorrhizae, also affect utilization of rock phosphate. Dissolution of rock phosphates may be too slow for rapidly growing crops but may be adequate for perennial crops.Such factors limit the use of rock phosphates for direct application, so that much greater knowledge of the characteristics of the phosphates, soils and crops, and their interactions, is necessary for their successful use than for the soluble phosphates. Economic considerations are important also. Because the phosphate content is less than that of concentrated soluble fertilizers, the cost of transporting rock phosphates, per unit of phosphorus, may not be economic. However, for acid and calcium deficient soils the larger amounts of calcium that rock phosphates supply may be an advantage and may lessen or eliminate the need for lime, especially for crops that require relatively large amounts of calcium.Fosfatos de roca en la agricultura

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Dyberg, Cecilia, Teodora Andonova, Thale Kristin Olsen, Bertha Brodin, Marcel Kool, Per Kogner, John Inge Johnsen, and Malin Wickström. "Inhibition of Rho-Associated Kinase Suppresses Medulloblastoma Growth." Cancers 12, no. 1 (December 26, 2019): 73. http://dx.doi.org/10.3390/cancers12010073.

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Medulloblastoma is one of the most common malignant brain tumor types in children, with an overall survival of 70%. Mortality is associated with metastatic relapsed tumors. Rho-associated kinases (ROCKs), important for epithelial-mesenchymal transition (EMT) and proper nervous system development, have previously been identified as a promising drug target to inhibit cancer growth and metastatic spread. Here, we show that ROCKs are expressed in medulloblastoma, with higher ROCK2 mRNA expression in metastatic compared to non-metastatic tumors. By evaluating three ROCK inhibitors in a panel of medulloblastoma cell lines we demonstrated that medulloblastoma cells were sensitive for pharmacological ROCK inhibition. The specific ROCK inhibitor RKI-1447 inhibited the tumorigenicity in medulloblastoma cells as well as impeded cell migration and invasion. Differential gene expression analysis suggested that ROCK inhibition was associated with the downregulation of signaling pathways important in proliferation and metastasis e.g., TNFα via NFκβ, TGFβ, and EMT. Expression of key proteins in these pathways such as RHOA, RHOB, JUN, and vimentin was downregulated in ROCK inhibited cells. Finally, we showed that ROCK inhibition by RKI-1447 suppressed medulloblastoma growth and proliferation in vivo. Collectively, our results suggest that ROCK inhibition presents a potential new therapeutic option in medulloblastoma, especially for children with metastatic disease.

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Journal articles on the topic 'ROC2'

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