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Kim, Chungho,Seon Lee, Hyo,Lee, Deokjae,Lee, Sang Don,Cho, Eun-Gyung,Yang, Soo Jung,Kim, Sang Bum,Park, Dongeun,Kim, Moon Gyo American Society of Hematology 2011 Blood Vol.117 No.4
<B>Abstract</B><P>Epithin/PRSS14, a type II transmembrane serine protease, is involved in normal epithelial development and tumor progression. Here we report, as an interacting substrate of epithin, a receptor tyrosine kinase Tie2 that is well known for important roles in the vessel stability. Epithin interacts with and degrades the Tie2 extracellular portion that contains the ligand-binding domain. Epithin is located in the neighbor of Tie2-expressing vessels in normal tissue. Furthermore, epithin can cleave and degrade Tie2 not only in the same cell but also from neighboring cells nearby, resulting in the degradation of the Tie2 ectodomain. The remaining Tie2 fragment was highly phosphorylated and was able to recruit a downstream effector, phosphatidylinositol 3-kinase. Knocking down epithin expression using short hairpin RNA in thymoma cell severely impaired the migration through endothelial cells that show the actin rearrangement during the process. The diminution of epithin protein expression in 4T1 breast cancer cells caused the significant decrease in the number of transendothelial migrating cells in vitro as well as in those of metastasizing tumor nodules in vivo, Therefore, we propose that epithin, which regulates endothelial Tie2 functions, plays a critical role in the fine tuning of transendothelial migration for normal and cancer cells.</P>
Kim, Jiyoon,Yang, Chansik,Kim, Eun Jin,Jang, Jungim,Kim, Se-Jong,Kang, So Min,Kim, Moon Gyo,Jung, Hosung,Park, Dongeun,Kim, Chungho The Company of Biologists Limited 2016 Journal of cell science Vol.129 No.10
<P>Vimentin, an intermediate filament protein induced during epithelialto- mesenchymal transition, is known to regulate cell migration and invasion. However, it is still unclear how vimentin controls such behaviors. In this study, we aimed to find a new integrin regulator by investigating the H-Ras-mediated integrin suppression mechanism. Through a proteomic screen using the integrin beta 3 cytoplasmic tail protein, we found that vimentin might work as an effector of H-Ras signaling. H-Ras converted filamentous vimentin into aggregates near the nucleus, where no integrin binding can occur. In addition, an increase in the amount of vimentin filaments accessible to the integrin beta 3 tail enhanced talin-induced integrin binding to its ligands by inducing integrin clustering. In contrast, the vimentin head domain, which was found to bind directly to the integrin beta 3 tail and compete with endogenous vimentin filaments for integrin binding, induced nuclear accumulation of vimentin filaments and reduced the amount of integrin-ligand binding. Finally, we found that expression of the vimentin head domain can reduce cell migration and metastasis. From these data, we suggest that filamentous vimentin underneath the plasma membrane is involved in increasing integrin adhesiveness, and thus regulation of the vimentin-integrin interaction might control cell adhesion.</P>
Graphene Oxide Assisted Synthesis of Self-assembled Zinc Oxide for Lithium-Ion Battery Anode
Kim, Chungho,Kim, Jin Wook,Kim, Hyunhong,Kim, Dong Hyeon,Choi, Changhoon,Jung, Yoon Seok,Park, Jongnam American Chemical Society 2016 Chemistry of materials Vol.28 No.23
<P>A simple method for the synthesis of a hierarchically self-assembled zinc oxide is presented, in which graphene oxide is used to assist in the assembly of the structure and improve the electrical conductivity of the ZnO. The self-assembled ZnO formed on graphene oxide exhibits a high specific capacity, while also demonstrating good rate performance and cycling stability due to the advantages of using both nanoparticles and a secondary structure.</P>
Lee, Hyo Seon,Oh, Seung Ja,Lee, Kwang-Hoon,Lee, Yoon-Sook,Ko, Eun,Kim, Kyung Eun,Kim, Hyung-chan,Kim, Seokkyun,Song, Paul H.,Kim, Yong-In,Kim, Chungho,Han, Sangyeul American Society for Biochemistry and Molecular Bi 2014 The Journal of biological chemistry Vol.289 No.45
<P>Angiopoietin-2 (Ang-2) not only regulates angiogenesis by binding to its well known receptor Tie2 on endothelial cells but also controls sprouting of Tie2-negative angiogenic endothelial cells and invasion of Tie2-negative non-endothelial cells by binding to integrins. However, the molecular mechanism of the Ang-2/integrin association has been unclear. In this study, we found that the Gln-362 residue of Ang-2 was essential for binding to α5β1 integrin. A Q362E Ang-2 mutant, which still bound to Tie2, failed to associate with α5β1 integrin and was unable to activate the integrin downstream signaling of focal adhesion kinase. In addition, unlike wild-type Ang-2, the Q362E Ang-2 mutant was defective in mediating invasion of Tie2-negative glioma or Tie2-positive endothelial cells. Furthermore, the tailpiece domain of the α5 subunit in α5β1 integrin was critical for binding to Ang-2. Taken together, these results provide a novel insight into the mechanism of integrin regulation by Ang-2, which contributes to tumor invasion and endothelial cell migration in a Tie2-independent manner.</P>
Filamin is essential for shedding of the transmembrane serine protease, epithin
Kim, Chungho,Cho, Yongcheol,Kang, Chan‐,Hee,Kim, Moon Gyo,Lee, HyoSeon,Cho, Eun‐,Gyung,Park, Dongeun EMBO 2005 EMBO reports Vol.6 No.11
<P>Epithin is a type II transmembrane serine protease that exists in a soluble and membrane-bound form. Shedding is thought to be important in regulating its action, but little is known regarding the intracellular events that trigger such shedding. Here, we show that phorbol myristate acetate (PMA) causes the release of epithin. It also causes accumulation of the protein at the site of cell-cell contacts, and this accumulation is dependent on the formation of cortical actin. In addition, we have identified the actin-binding protein, filamin, as the linker between epithin and the actin cytoskeleton. The interaction of epithin and filamin was enhanced by PMA, and epithin was not released from filamin-deficient M2 cells. We also show that the release of epithin does not require its own activity and is blocked by a metalloprotease inhibitor, GM6001. These results show that filamin has an essential role in shedding by linking epithin to the as yet unidentified metalloprotease-shedding enzyme(s).</P>
난소 적출 흰쥐 골다공증 모델에서 금은화(金銀花)가 골밀도 증가에 미치는 효과
이성엽 ( Sungyub Lee ),김민선 ( Minsun Kim ),홍수연 ( Sooyeon Hong ),김재현 ( Jae-hyun Kim ),김홍식 ( Hongsik Kim ),이충호 ( Chungho Lee ),정혁상 ( Hyuk-sang Jung ),손영주 ( Youngjoo Sohn ) 대한본초학회 2021 大韓本草學會誌 Vol.36 No.5
Objectives : Osteoporosis is a systemic skeletal disease that decreases bone density and increases the risk of fractures. Bisphosphonates and SERMs are mainly used to treat osteoporosis, but, long-term use increases the risk of side effects such as jaw bone necrosis and breast cancer. Therefore, it is necessary to develop a therapeutic agent for a natural product with few side effects. Water extract of Lonicerae Japonicae Flos (wLF) was mainly found to have anti-cancer and anti-inflammatory effects. However, the effect of wLF on osteoporosis has not been elucidated. Therefore, this experiment investigated the effect of wLF on osteoclasts, osteoblasts and osteoporosis models. Methods : In order to study the effect of wLF on osteoporosis, the OVX-induced rat model was used for in vivo study. After 8 weeks, we measured body weight, uterine weight, liver weight, femur weight, bone density, trabecular area and tibia ash weight. To determine the effect of wLF on osteoclast differentiation, we measured the number of TRAP-positive cells and TRAP activity. To examine the effect of wLF on the expression of osteoblast-related genes, we measured the mRNA expression of alkaline phosphatase (ALP, Alpl) and osteocalcin (OCN, Bglap2). Results : In vivo experiment, wLF inhibited the reduction of femur weight, trabecular area, bone density and tibia ash weight. In vitro experiment, wLF had no significant effect on osteoclast differentiation. However, wLF increased the mRNA expression of Alpl and Bglap2 in MC3T3-E1 cell. Conclusions : This result suggested that wLF may be used for the treatment and prevention of postmenopausal osteoporosis.
Yang, Chansik,Ohk, Jiyeon,Lee, Ji Yeun,Kim, Eun Jin,Kim, Jiyoon,Han, Sangyeul,Park, Dongeun,Jung, Hosung,Kim, Chungho American Heart Association, Inc. 2016 Arteriosclerosis, thrombosis, and vascular biology Vol.36 No.7
<P>Objective-Angiogenesis, the process of building complex vascular structures, begins with sprout formation on preexisting blood vessels, followed by extension of the vessels through proliferation and migration of endothelial cells. Based on the potential therapeutic benefits of preventing angiogenesis in pathological conditions, many studies have focused on the mechanisms of its initiation as well as control. However, how the extension of vessels is terminated remains obscure. Thus, we investigated the negative regulation mechanism. Approach and Results-We report that increased intracellular calcium can induce dephosphorylation of the endothelial receptor tyrosine kinase Tie2. The calcium-mediated dephosphorylation was found to be dependent on Tie2-calmodulin interaction. The Tyr1113 residue in the C-terminal end loop of the Tie2 kinase domain was mapped and found to be required for this interaction. Moreover, mutation of this residue into Phe impaired both the Tie2-calmodulin interaction and calcium-mediated Tie2 dephosphorylation. Furthermore, expressing a mutant Tie2 incapable of binding to calmodulin or inhibiting calmodulin function in vivo causes unchecked growth of the vasculature in Xenopus. Specifically, knockdown of Tie2 in Xenopus embryo retarded the sprouting and extension of intersomitic veins. Although human Tie2 expression in the Tie2-deficient animals almost completely rescued the retardation, the Tie2(Y1113F) mutant caused overgrowth of intersomitic veins with strikingly complex and excessive branching patterns. Conclusions-We propose that the calcium/calmodulin-dependent negative regulation of Tie2 can be used as an inhibitory signal for vessel growth and branching to build proper vessel architecture during embryonic development.</P>
Jiyoung Jang,조은혜,Youngkyung Cho,Binderya Ganzorig,Ki Yeon Kim,Moon Gyo Kim,Chungho Kim 한국분자세포생물학회 2022 Molecules and cells Vol.45 No.8
Epithin/PRSS14 is a membrane serine protease that plays a key role in tumor progression. The protease exists on the cell surface until its ectodomain shedding, which releases most of the extracellular domain. Previously, we showed that the remaining portion on the membrane undergoes intramembrane proteolysis, which results in the liberation of the intracellular domain and the intracellular domainmediated gene expression. In this study, we investigated how the intramembrane proteolysis for the nuclear function is initiated. We observed that ectodomain shedding of epithin/PRSS14 in mouse breast cancer 4T1 cells increased depending on environmental conditions and was positively correlated with invasiveness of the cells and their proinvasive cytokine production. We identified selenite as an environmental factor that can induce ectodomain shedding of the protease and increase C-C motif chemokine ligand 2 (CCL2) secretion in an epithin/PRSS14-dependent manner. Additionally, by demonstrating that the expression of the intracellular domain of epithin/PRSS14 is sufficient to induce CCL2 secretion, we established that epithin/PRSS14- dependent shedding and its subsequent intramembrane proteolysis are responsible for the metastatic conversion of 4T1 cells under these conditions. Consequently, we propose that epithin/PRSS14 can act as an environment-sensing receptor that promotes cancer metastasis by liberating the intracellular domain bearing transcriptional activity under conditions promoting ectodomain shedding.
LP loop EGR 디젤 엔진의 EGR cooler 적용 특성
정재우(Jaewoo Chung),정동영(Dongyoung Jeong),김남호(Namho Kim),강정호(Chungho Kang),서영호(Youngho Seo),김병수(Byoungsu Kim),김태진(Taejin Kim) 한국자동차공학회 2010 한국자동차공학회 학술대회 및 전시회 Vol.2010 No.11
In this study, an EGR system of EURO4 engine was modified to LP loop EGR system considering the minimize the pressure drop and LP EGR cooler application characteristics was investigated using various EGR cooler applications. As the investigation , LP EGR cooler fouling test was performed during 50 hr at LP loop EGR engine driving condition and as the fouling test result, EGR cooler fouling phenomena did not happened. Also, EGR gas cooling performance and pressure drop through EGR cooler was measured at engine test. From LP loop EGR engine tests, Engine fuel economy performance was improved about 4%∼7% compared with the base EURO 4 engine value at similar NOx emission level, And it is found that intake manifold temperature is effected by EGR cooler, EGR/ fresh air mixing and intercooler cooling capacity. On the other hand, EGR cooler has some effects on cooling the EGR gas upstream of EGR valve and compressor, EGR cooler restrict the gas temperature in LP EGR system and protect the LP EGR components. So high EGR rate could be realized by application of a LP EGR cooler. In Hybrid EGR system, monitoring of LP EGR fraction has been point out as a technical problem, so, in this study, a LP EGR mass flow rate measurement method using EGR cooler was made to attempt.