• Title/Summary/Keyword: gp130

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Janus Kinase 2 Inhibitor AG490 Inhibits the STAT3 Signaling Pathway by Suppressing Protein Translation of gp130

  • Seo, In-Ae;Lee, Hyun-Kyoung;Shin, Yoon-Kyung;Lee, Sang-Hwa;Seo, Su-Yeong;Park, Ji-Wook;Park, Hwan-Tae
    • The Korean Journal of Physiology and Pharmacology
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    • v.13 no.2
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    • pp.131-138
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    • 2009
  • The binding of interleukin-6 (IL-6) cytokine family ligands to the gp130 receptor complex activates the Janus kinase (JAK)/ signal transducer and activator of transcription 3 (STAT3) signal transduction pathway, where STA T3 plays an important role in cell survival and tumorigenesis. Constitutive activation of STAT3 has been frequently observed in many cancer tissues, and thus, blocking of the gp130 signaling pathway, at the JAK level, might be a useful therapeutic approach for the suppression of STAT3 activity, as anticancer therapy. AG490 is a tyrphostin tyrosine kinase inhibitor that has been extensively used for inhibiting JAK2 in vitro and in vivo. In this study, we demonstrate a novel mechanism associated with AG490 that inhibits the JAK/STAT3 pathway. AG490 induced downregulation of gp130, a common receptor for the IL-6 cytokine family compounds, but not JAK2 or STAT3, within three hours of exposure. The downregulation of gp130 was not caused by enhanced degradation of gp130 or by inhibition of mRNA transcription. It most likely occurred by translation inhibition of gp130 in association with phosphorylation of the eukaryotic initiation factor-2 a. The inhibition of protein synthesis of gp130 by AG490 led to immediate loss of mature gp130 in cell membranes, due to its short half-life, thereby resulting in reduction in the STAT3 response to IL-6. Taken together, these results suggest that AG490 blocks the STAT3 activation pathway via a novel pathway.

GP130 cytokines and bone remodelling in health and disease

  • Sims, Natalie A.;Walsh, Nicole C.
    • BMB Reports
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    • v.43 no.8
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    • pp.513-523
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    • 2010
  • Cytokines that bind to and signal through the gp130 co-receptor subunit include interleukin (IL)-6, IL-11, oncostatin M (OSM), leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), and ciliary neutrophic factor (CNTF). Apart from contributing to inflammation, gp130 signalling cytokines also function in the maintenance of bone homeostasis. Expression of each of these cytokines and their ligand-specific receptors is observed in bone and joint cells, and bone-active hormones and inflammatory cytokines regulate their expression. gp130 signalling cytokines have been shown to regulate the differentiation and activity of osteoblasts, osteoclasts and chondrocytes. Furthermore, cytokine and receptor specific gene-knockout mouse models have identified distinct roles for each of these cytokines in regulating bone resorption, bone formation and bone growth. This review will discuss the current models of paracrine and endocrine actions of gp130-signalling cytokines in bone remodelling and growth, as well as their impact in pathologic bone remodelling evident in periodontal disease, rheumatoid arthritis, spondylarthropathies and osteoarthritis.

Tyrphostin ErbB2 Inhibitors AG825 and AG879 Have Non-specific Suppressive Effects on gp130/ STAT3 Signaling

  • Lee, Hyun-Kyoung;Seo, In-Ae;Lee, Sang-Hwa;Seo, Su-Young;Kim, Kyung-Sup;Park, Hwan-Tae
    • The Korean Journal of Physiology and Pharmacology
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    • v.12 no.5
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    • pp.281-286
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    • 2008
  • Although the interaction between gp130 and the ErbB family has frequently been shown in cancer cells, the mechanism of this interaction remains unclear and controversial. In the present study, we found that specific tyrphostin inhibitors of ErbB2 (AG825 and AG879), but not ErbB1 inhibitor (AG1478), suppressed IL-6-induced tyrosine phosphorylation of STAT3 in schwannoma cells. However, biochemical evidence for transactivation of ErbB2 by IL-6 was not observed. Additionally, the inhibition of ErbB2 expression, with either a specific RNAi or transfection of an ErbB2 mutant lacking the intracellular domain did not inhibit the IL-6-induced tyrosine phosphorylation of STAT3. Thus, it seems that tyrphostins, which are known as specific inhibitors of the ErbB2 kinase, may have non-specific suppressive effects on the IL-6/STAT3 pathway.

PROM1-mediated cell signal transduction in cancer stem cells and hepatocytes

  • Myeong-Suk Bahn;Young-Gyu Ko
    • BMB Reports
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    • v.56 no.2
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    • pp.65-70
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    • 2023
  • Prominin-1 (PROM1), also called CD133, is a penta-span transmembrane protein that is localized in membrane protrusions, such as microvilli and filopodia. It is known to be expressed in cancer stem cells and various progenitor cells of bone marrow, liver, kidney, and intestine. Accumulating evidence has revealed that PROM1 has multiple functions in various organs, such as eye, tooth, peripheral nerve, and liver, associating with various molecular protein partners. PROM1 regulates PKA-induced gluconeogenesis, TGFβ-induced fibrosis, and IL-6-induced regeneration in the liver, associating with Radixin, SMAD7, and GP130, respectively. In addition, PROM1 is necessary to maintain cancer stem cell properties by activating PI3K and β-Catenin. PROM1-deficienct mice also show distinct phenotypes in eyes, brain, peripheral nerves, and tooth. Here, we discuss recent findings of PROM1-mediated signal transduction.

Pro-inflammatory Cytokines and Their Receptors: Expression and Regulation in the Uterine Endometrium during the Estrous Cycle in Pigs

  • Yoo, Inkyu;Kim, Minjeong;Han, Jisoo;Jang, Hwanhee;Choi, Sun-Ho;Ka, Hakhyun
    • Journal of Embryo Transfer
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    • v.31 no.4
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    • pp.323-333
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    • 2016
  • Pro-inflammatory cytokines, interleukin-$1{\beta}$(IL1B), IL6, and tumor necrosis factor-alpha (TNF), are known to play important roles in regulating the endometrial function in the uterus during the estrous cycle and pregnancy in several species. However, the expression and function of these cytokines and their receptors in the uterine endometrium during the estrous cycle have not been studied in pigs. Thus, this study determined the expression and regulation of IL1B, IL6, TNF and their respective receptors, IL1R1, IL1RAP, IL6R, GP130, TNFRSF1A, and TNFRSF1B during the estrous cycle in pigs. To analyze levels of each gene expression in the uterine endometrium we obtained from endometrial tissues on Days 0, 3, 6, 9, 12, 15, and 18 of the estrous cycle. Real-time RT-PCR analysis showed that levels of IL1B, IL1RAP, IL6R, GP130, TNF, TNFRSF1A, and TNFRSF1B mRNAs were highest on Day 15 or 18 of the estrous cycle, which corresponds to the proestrus period. Levels of IL1R1 were highest on Day 0, while levels of IL6 were biphasic with high levels on Day 6 and Day 15. The abundance of IL1B, IL6, IL6R, and TNF mRNAs was decreased by progesterone, while levels of GP130 were increased by progesterone in endometrial tissue explants. These results showed that expression of pro-inflammatory cytokines and their receptors changed stage-specifically during the estrous cycle and regulated by progesterone in the uterine endometrium in pigs, suggesting that these pro-inflammatory cytokines may be involved in the regulation endometrial function during the estrous cycle in pigs.

Automated external defibrillator electrode pad placement by the general public and health-care providers : A manikin study (일반인 및 의료종사자들의 자동제세동기를 이용한 제세동에서 전극부착 위치에 관한 연구: 마네킨을 이용한 연구)

  • Park, Si-Eun
    • The Korean Journal of Emergency Medical Services
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    • v.20 no.1
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    • pp.83-94
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    • 2016
  • Purpose: This study aimed to assess defibrillator pad positioning by the general public and healthcare providers during basic life support (BLS) renewal education (RE). Methods: A total 130 subjects performed defibrillation using an automated external defibrillator (AED) equipped with electrode pads developed by the researchers and male resuscitation manikins, in order to assess electrode pad placement (EPP) before BLS RE. Subjects included 54 Healthcare providers (HP) and 76 members of the general public (GP). Results: The apex EPP was positioned in the risk area (RA), more than 5 cm distant from the area recommended, by 63.2% of the GP (n = 48). The apex EPP was positioned in the RA by 44.4% of the HP (n = 23). The distance from the apex (GP $5.27{\pm}2.21cm$, HP $4.18{\pm}1.71cm$) was statistically significant, using Student's t-test. Conclusion: For both GP and HP, apex EPP was significantly in error. Thus, to prevent defibrillation failures, EPP education and practice for GP and HP in all BLS education programs should be improved, and incorrect Korean cardiopulmonary resuscitation guidelines and related literature should be revised and corrected.

마이크로 컴퓨터와 계측기의 인터페이스

  • 오재응
    • Journal of the KSME
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    • v.28 no.2
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    • pp.130-137
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    • 1988
  • (1) IBM-XT와 SD375를 GP-IB로 인터페이스 시킴에 있어서 여러 가지 문제점이 발생되었지만 문제점의 해결과정을 통하여 인터페이스의 일반적인 지식을 얻을 수 있었고 그 지식을 바탕으로 컴퓨터를 이용하여 계측기의 제어를 할 수 있었다. (2) 마이크로 컴퓨터를 이용하여 계측기를 제어함으로써 계측 제어의 기초를 형성하였으며, 앞으로 로봇을 도입하여 각종 계측기들이 복 합적으로 구성된 자동 계측시스템을 만들 수 있는 실력 습득의 계기가 되었다.

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Design and Implementation of Combined RF Receiver Front End for GPS/GLONASS (GPS/ GLONASS 통합 수신용 RF 전단부의 설계 및 제작)

  • 주재순;염경환;이상정
    • The Journal of Korean Institute of Electromagnetic Engineering and Science
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    • v.12 no.4
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    • pp.494-502
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    • 2001
  • GPS(Global Positioning System) and GLONASS(GLObal Navigation Satellite System) are basic technologies providing the information of the position and the time, and they have various applications such as navigation, survey, control, and so on. However, each GPS and GLONASS has limited number of visible satellites, and, from the view of strategy, it is undesirable to be heavily dependent on only one system. Thus, GPS/GLONASS combined receiver became required to obtain more precise navigation and system stability. In this paper, the RF front end of GPS/GLONASS combined receiver was fabricated on 130$\times$80 $\textrm{mm}^2$ PCB(Printed Circuit Board), and its system application was shown finally one chip possibility of GLONASS receiver is studied.

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GPS Surveying for Intersection Improvements (교차로 구조개선을 위한 GPS측량)

  • Kim, Seok-Jong;Shon, Ki-Hyun
    • Journal of Korean Society for Geospatial Information Science
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    • v.2 no.2 s.4
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    • pp.125-130
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    • 1994
  • The original concept of GPS is the feature of instantaneous navigation which is the determination of the position of a moving vehicle(ie, a ship, a car, an air craft) by unsmoothed code pseudoranges. The objective of study is compare the efficiency (or time, accuracy) between GPS surveying by using kinematic method and conventional surveying methods in the intersection, and then suggest research materials for actual application.

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Comparative Evaluation of Drug Use for Outpatients Prescribed by General Practitioner and Specialized Practitioner in ENT Area (이비인후과 영역에서 일반의와 전문의에 의한 외래처방전의 비교 평가)

  • Min, Hyun-Seong;Song, Tae-Beom;Lee, Myung-Koo;Jang, Je-Kwan;Lee, Chong-Kil;Lim, Sung-Cil
    • YAKHAK HOEJI
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    • v.54 no.4
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    • pp.258-269
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    • 2010
  • As people are easy to access the National Health Insurance, medical health service has been increased. It contributed to extend human's average life expectancy and to get better health care. But also increased unnecessary health service or inappropriate drug use. Therefore, DUR (Drug Use Review) is needed to induce appropriate drug use. The purpose of this study is to evaluate outpatient prescriptions by General Practitioner (GP) and Specialized Practitioner, especially indication for ENT referral including common cold which is the frequent indications that have patient see doctor. This study was reviewed retrospectively prescriptions for ENT referral collected at the A pharmacy for ENT Clinic in Cheong-Ju, B pharmacy for GP Clinic in BoEun from Feb 2nd, 2009 to Feb 28th, 2009. Each pharmacy located closed to the each enrolled clinic. The numbers of collected prescriptions were each A pharmacy (n=2501), B pharmacy (n=1343). This study was classified Drug Related Problems (DRPs) those prescriptions had as total 6 groups according to following 6 categories; 1) Unnecessary Drug, 2) Wrong Drug, 3) Low Dose, 4) Overdose, 5) Wrong Instruction, 6) Wrong Combination. In results, Specialized Practitioner's prescriptions had more DRPs than General Practitioner's prescriptions (ENT 155.34% vs GP 130.01%). In detail, Specialized Practitioner's prescriptions had more DRPs in Low Dose (ENT 16.95% vs GP 4.77%), Overdose (ENT 6.72% vs G.P 5.51%), Wrong Instruction (ENT 7.91% vs GP 5.81%), Wrong Combination (ENT 29.31% vs GP 25.09%). These DRPs would be caused from lack of consideration for dosage and drug interaction. General Practitioner's prescriptions had more DRPs in Unnecessary Drug (ENT 70.37% vs GP 78.85%), Wrong drug (ENT 4.12% vs GP 9.98%). These DRPs would be associated with drug selection. This study was assumed that Specialized Practitioner is better prescriber than General Practitioner because Specialized Practitioner complete additional intern and residency training. But, Specialized Practitioner is not always better prescriber than General Practitioner. Furthermore, prescriptions of both Specialized Practitioner and General Practitioner had many problems. In conclusion, It could be cut down the excessive medical expense and expected more efficient medical care by reducing DRPs, thus contributing to the improvement of national health. In order to pharmacist must have good professional ability of pharmacotherapy to help the physician for the drug selection.