• Title/Summary/Keyword: K-Ras

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A Genome-wide Scan for Selective Sweeps in Racing Horses

  • Moon, Sunjin;Lee, Jin Woo;Shin, Donghyun;Shin, Kwang-Yun;Kim, Jun;Choi, Ik-Young;Kim, Jaemin;Kim, Heebal
    • Asian-Australasian Journal of Animal Sciences
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    • v.28 no.11
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    • pp.1525-1531
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    • 2015
  • Using next-generation sequencing, we conducted a genome-wide scan of selective sweeps associated with selection toward genetic improvement in Thoroughbreds. We investigated potential phenotypic consequence of putative candidate loci by candidate gene association mapping for the finishing time in 240 Thoroughbred horses. We found a significant association with the trait for Ral GApase alpha 2 (RALGAP2) that regulates a variety of cellular processes of signal trafficking. Neighboring genes around RALGAP2 included insulinoma-associated 1 (INSM1), pallid (PLDN), and Ras and Rab interactor 2 (RIN2) genes have similar roles in signal trafficking, suggesting that a co-evolving gene cluster located on the chromosome 22 is under strong artificial selection in racehorses.

Mitogen-activated $p70^{s6k}$ signalling pathway

  • Han, Jeung-Whan
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.11a
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    • pp.135-139
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    • 1996
  • $p70^{s6k}$ lies on a $p21^{ras}$-independent signalling pathway and plays an important role in mitogenesis. Activation is associated with phosphorylation at multiple sites, four of which lie in an autoinhibitory region. The immunosuppressant rapamycin induces $p70^{s6k}$ inactivation through dephosphorylation of a second set of mitogen-induced sites. Here we identify these sites as $T_{229}$, $T_{389}$, and $S_{404}$. $T_{229}$ resides in the "T loop" of the catalytic domain, an essential phosphorylation site in other kinases. However, $p70^{s6k}$ inactivation by rapamycin most closely parallels $T_{389}$ dephosphorylation. Mutation of $T_{389}$ to alanine ablates kinase activity, whereas mutation to glutamic acid confers constitutive kinase activity and rapamycin resistance. indicating an essential role for phosphorylation at this site. $T_{389}$ resides in an unusual hydrophobic motif, not previously noted, between the catalytic and autoinhibitory domains. The importance of this site, and surrounding motif, is emphasized by its conservation in other kinases including homologues of $p70^{s6k}$ derived from such distantly related organisms as yeast and plant.

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Simulation of Subnet Management for InfiniBand (채널 기반 인피니밴드의 서브넷 관리를 위한 시뮬레이션)

  • Kim, Young-Hwan;Youn, Hee-Yong;Park, Chang-Won;Lee, Hyoung-Su;Go, Jae-Jin;Park, Sang-Hyun
    • Proceedings of the Korea Information Processing Society Conference
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    • 2002.11a
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    • pp.535-538
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    • 2002
  • InfiniBand is a switched-fabric architecture for next generation I/O systems and data centers. The InfiniBand Architecture (IBA) promises to replace bus-based architectures, such as PCI, with a switched-based fabric whose benefits include higher performance, higher RAS (reliability, availability, scalability), and the ability to create modular networks of servers and shared I/O devices. The switched-fabric InfiniBand consists of InfiniBand subnets with channel adapters, switches, and routers. In order to fully grasp the operational characteristics of InfiniBand architecture (IBA) and use them in ongoing design specification, simulation of subnet management of IBA is inevitable. In this paper, thus, we implement an IBA simulator and test some practical sample networks using it. The simulator shows the flow of operation by which the correctness and effectiveness of the system can be verified.

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The SH3 Domain of Phospholipase C-${\gamma}1$ Associates with Shc

  • Kim, Myung-Jong;Hwang, Jong-Ik;Chang, Jong-Soo;Ryu, Sung-Ho;Suh, Pann-Ghill
    • BMB Reports
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    • v.32 no.2
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    • pp.119-126
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    • 1999
  • The SH3 domain of PLC-${\gamma}1$ has been known to induce DNA synthesis. However, little is known about the putative effector proteins that associate with the domain. In this report, we provide evidence that the SH3 domain of PLC-${\gamma}1$ associates with Shc, which has been implicated in the activation of p21Ras in response to many growth factors. The association between Shc and PLC-${\gamma}1$ is enhanced either by v-Src-induced transformation or EGF-stimulation in vivo and in vitro. Furthermore, from transient expression studies with COS-7 cells, we show that the SH3 domain of PLC-${\gamma}1$ is required for association with Shc in vivo, whereas tyrosyl phosphorylation of PLC-${\gamma}1$ is not. Taken together, we suggest that Shc might be involved in the PLC-${\gamma}1$-mediated signaling pathway.

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RASA1-Related Parkes Weber Syndrome in a Neonate

  • Koh, Hong Ryul;Lee, Yeon Kyung;Ko, Sun Young;Shin, Son Moon;Han, Byoung-Hee
    • Neonatal Medicine
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    • v.25 no.3
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    • pp.126-130
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    • 2018
  • Parkes Weber syndrome is a rare congenital vascular anomaly, related to the RAS p21 protein activator 1 (RASA1) gene. It is characterized by capillary cutaneous malformations, bony and soft tissue hyperplasia, and multiple arteriovenous fistulas throughout the affected upper or lower extremity. These arteriovenous fistulas can be associated with life-threatening complications such as bleeding, thrombosis, and high output heart failure. In this report, we present a neonate who had a disproportionately hypertrophied left upper limb with port-wine stain, dystrophy of the left humerus, and hypertrophy of the left clavicle on X-ray, and arteriovenous malformation and massive dilatation of the left subclavian artery on magnetic resonance angiography. Exome sequencing analysis revealed a novel heterozygous splicing mutation (c.1776+2T>A) in the RASA1 gene. To the best of our knowledge, this report is the first case of RASA1-related Parkes Weber syndrome in Korea.

Methylation Profile of BRCA1, RASSF1A and ER in Vietnamese Women with Ovarian Cancer

  • Lan, Vo Thi Thuong;Thuan, Ta Bich;Thu, Doan Minh;Uyen, Nguyen Quynh;Ha, Ngo Thi;To, Ta Van
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7713-7718
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    • 2013
  • DNA methylation is considered a promising biomarkers for diagnosis of cancer in general and of ovarian cancer in particular. In our study, we validated the accuracy of methylation specific polymerase chain reaction (MSP) to analyze the methylation pattern of BRCA1, RASSF1A and ER in 59 and 10 Vietnamese patients with epithelial ovarian cancer (EOC) and benign ovarian tumors, respectively. We found methylation of BRCA1, RASSF1A and ER in 11/59 (18.6%), 40/59 (67.8%) and 15/59 (25.4%) of EOC cases, while methylation of BRCA1 was only detected in 2/10 (20%) benign ovarian patients. Forty five out of the 59 EOCs (78%) demonstrated methylation at one or more genes. The methylation frequency of RASSF1A was significantly associated with EOC (p<0.0005). No significant association was observed between methylation status of these genes and the clinical and pathological parameters of tumors collected from Vietnamese women suffering from ovarian cancer.

Aberrant Methylation of RASSF1A gene Contribute to the Risk of Renal Cell Carcinoma: a Meta-Analysis

  • Yu, Gan-Shen;Lai, Cai-Yong;Xu, Yin;Bu, Chen-Feng;Su, Ze-Xuan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4665-4669
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    • 2015
  • The aim of this study was to assess the diagnostic value of RASSF1A methylation in renal cell carcinoma. Systematically search were performed using the Pubmed, ProQest and Web of Science for all articles on the association between RASSF1A methylation and renal cell carcinoma before 15 April 2015. After the filtration, 13 studies involving 677 cases and 497 controls met our criteria. Our meta-analysis suggested that hypermethylation of RASSF1A gene was associated with the increased risk of RCC(OR:4.14, 95%CI:1.06-16.1). Stratified analyses showed a similar risk in qualitative detection method(OR:28.4, 95%CI:10.2-79.6), body fluid sample(OR:12.8, 95%CI:5.35-30.8), and American(OR:10.5, 95%CI:1.97-55.9). Our result identified that RASSF1A methylation had a strong potential in prediction the risk of Renal cell carcinoma.

Identification of simvastatin-regulated targets associated with JNK activation in DU145 human prostate cancer cell death signaling

  • Jung, Eun Joo;Chung, Ky Hyun;Kim, Choong Won
    • BMB Reports
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    • v.50 no.9
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    • pp.466-471
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    • 2017
  • The results of this study show that c-Jun N-terminal kinase (JNK) activation was associated with the enhancement of docetaxel-induced cytotoxicity by simvastatin in DU145 human prostate cancer cells. To better understand the basic molecular mechanisms, we investigated simvastatin-regulated targets during simvastatin-induced cell death in DU145 cells using two-dimensional (2D) proteomic analysis. Thus, vimentin, Ras-related protein Rab-1B (RAB1B), cytoplasmic hydroxymethylglutaryl-CoA synthase (cHMGCS), thioredoxin domain-containing protein 5 (TXNDC5), heterogeneous nuclear ribonucleoprotein K (hnRNP K), N-myc downstream-regulated gene 1 (NDRG1), and isopentenyl-diphosphate Delta-isomerase 1 (IDI1) protein spots were identified as simvastatin-regulated targets involved in DU145 cell death signaling pathways. Moreover, the JNK inhibitor SP600125 significantly inhibited the upregulation of NDRG1 and IDI protein levels by combination treatment of docetaxel and simvastatin. These results suggest that NDRG1 and IDI could at least play an important role in DU145 cell death signaling as simvastatinregulated targets associated with JNK activation.

ERK1/2 activation by the C. elegans muscarinic acetylcholine receptor GAR-3 in cultured mammalian cells involves multiple signaling pathways

  • Shin, Young-Mi;Shin, Young-Ju;Kim, Seung-Woo;Park, Yang-Seo;Cho, Nam-Jeong
    • Animal cells and systems
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    • v.14 no.3
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    • pp.155-160
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    • 2010
  • Extracellular signal-regulated kinases 1/2 (ERK1/2) play important roles in a variety of biological processes including cell growth and differentiation. We have previously reported that GAR-3 activates ERK1/2 via phospholipase C and protein kinase C, presumably through pertussis toxin (PTX)-insensitive Gq proteins, in Chinese hamster ovary (CHO) cells. Here we provide evidence that GAR-3 also activates ERK1/2 through PTX-sensitive G proteins, phosphatidylinositol 3-kinase (PI 3-kinase), and Src family kinases in CHO cells. We further show that in human embryonic kidney (HEK293) cells, epidermal growth factor receptor and Ras are required for efficient ERK1/2 activation by GAR-3. Taken together, our data indicate that GAR-3 evokes ERK1/2 activation through multiple signaling pathways in cultured mammalian cells.

The Factor Analysis of Science Study in the Recognitive Aspect on the International Astronomy Olympiad Problems (국제천문올림피아드 문제에 나타난 인지적 측면의 과학 탐구 요소 분석)

  • Choe, Seung-Urn;Yim, In-Sung
    • Journal of the Korean earth science society
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    • v.25 no.8
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    • pp.719-730
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    • 2004
  • The International Astronomy Olympiad (IAO) was established and its foundation were published by the Euro-Asian Astronomical Society (EAAS), in order to spread astronomical knowledge, promote international cooperation in astronomical education area, and recognize the importance of astronomy in far-reaching field of science and human culture. In 1996, the first IAO was held at the Special Astrophysical Observatory (SAO) of the Russian Academy of sciences (RAS) located in the north Caucasus of Russia. Since then, it has been held every year. Here, we will describe the present status of the International Astronomy Olympiad, its major results by year, related institutions, organizations, and the main regulations regarding its operation. In order to measure the levels of scientific knowledge and thinking abilities, we develop a rubric to analyze the characteristics of problems in the IAO with regards to cognitive aspects of scientific inquiry. These problems require high levels of content knowledge and scientific method knowledge. Also high order thinking abilities and high levels of convergent thinking skills, instead of divergent, are needed to solve these problems. Thus, the problems presented are set a high difficulty. Through this analysis, we can understand main purpose of the International Astronomy Olympiad and explore the future direction of the Korea Astronomy Olympiad.