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Phosphorylation on TRPV4 Serine Residue 824 Enhances Its Association with PGM1

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American Journal of Molecular Biology 2016年第1期6卷 33-44页

作者： sung hwa shin Eun Jeoung Lee sunghee Hyun Sang Sun Kang Department of Biology Education Chungbuk National University Cheongju Republic of Korea Department of Internal Medicine Chungbuk National University Cheongju Republic of Korea Department of Biomedical Laboratory Science Eulji University Daejeon Republic of Korea

The TRPV4 cation channel is expressed in a broad range of tissues and participates in the generation of a Ca2+ signal and/or depolarization of membrane potential. Here, human phosphoglucomutase- 1 (PGM1), an enzyme that converts glucose-6 phosphate to glucose-1 phosphate in the glycolysis pathway, as the first auxiliary protein of TRPV4 Ca2+ channels, is identified with yeast two hybrid system, coimmunoprecipitation, confocal microscopy, and GST pull-down assays. TRPV4 forms a complex with PGM1 through its C-terminal cytoplasmic domain. Because it is demonstrated that TRPV4 serine residue 824 (S824) is phosphorylated by serum/glucocorticoid regulated kinase 1, we elucidate the effect of TRPV4 S824 phosphorylation on TRPV association with PGM1. Even an inactivated mutant version of TRPV4, S824A, exhibited a decreased ability to bind PGM1, an activated phosphomimetic mutant version of TRPV4, S824D, exhibited enhanced binding to PGM1. Thus, formation of the TRPV4/PGM1 complex and localization of this complex to the plasma membrane appear to be regulated by the phosphorylation status of residue S824 in TRPV4. The newly identified interactor of TRPV4 may help the molecular pathways modulating transport activity or glucose metabolism, respectively.

关键词： Membrane Localization Phosphoglucomutase1 Phosphorylation Protein-Protein Interaction TRPV4

SGK1 Inhibits ULK2 Autophagy Activity

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American Journal of Molecular Biology 2020年第1期10卷 12-28页

作者： sung hwa shin Eun Jeoung Lee sunghee Hyun Sang Sun Kang Department of Biology Education Chungbuk National University Cheongju Korea Department of Biomedical Laboratory Science Eulji University Daejeon Korea

Serum- and glucocorticoid-induced kinase 1 (SGK1) is known to have consensus sequence of phosphorylation site R-x-R-x-x-(S/T)-Φ, where Φ is any hydrophobic amino acid and arginine residues are conserved at positions −5 and −3 relative to positions of Ser/Thr residues that are phosphorylated in the presence of SGK1. UNC-21-like kinase 2 (ULK2) also harbors putative SGK1 phosphorylation sites at both Ser507 (502RsRnsSG508) and Ser750 (745RtRttSV751) residues. Thus, the objective of this study was to determine whether Ser507 and Ser750 residues of ULK2 could be phosphorylation sites of SGK1 as one of its authentic substrate proteins. Using ULK2 507 and 750 serine residue un- or phosphorylation analog (S507AS750A or 507DS750D), we observed that modification of Ser507 or Ser750 residue was required to activate the kinase activity of ULK2 and sensitize ULK2 to stress or starvation while simultaneously enhancing its active state and autophagy characteristics, suggesting that phosphorylation at Ser750 or Ser507 residue could modulate its subcellular localization and protein interaction with AMPK1α to activate ULK2. We also observed that ULK2 autophagy activity was enhanced by GSK650394 (an SGK1 inhibitor) to compensate survival capacity through increasing its association with LC3 and phosphorylation. When SGK1 known to be associated with cell survival was inhibited by GSK650394, ULK2 autophagy pathway was activated to avoid cell death alternatively. Thus, our observations indicate that phosphorylation of ULK2 by SGK1 can regulate cell survival as an alternative modulation of ULK2 functions.

关键词： ULK-2 SGK1 Phosphorylation Autophagy Cell Survival Signal Transduction

Ablation of TRPV4 in HepG2 with Its CRISPR/Cas9 Enhances Its Wound Healing

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American Journal of Molecular Biology 2020年第1期10卷 74-89页

作者： Eun Jeoung Lee sung hwa shin sunghee Hyun Sang Sun Kang CdmoGen Cheongju Republic of Korea Department of Pre-Medicine School of Medicine Eulji University Daejeon Republic of Korea Department of Biology Education Chungbuk National University Cheongju Republic of Korea

TRPV4 activity modulates cell activities including receptor trafficking and transcriptional or translational regulations. We tested its CRISPR/Cas9 scissor efficacy in HepG2 (HEK293) cell noticed that it worked well in both cell lines to eliminate TRPV4 genome sequences. To confirm TRPV4 functions in the cell morphology maintenance and cell growth (beyond Ca2+ channel), we compared its wound healing, cell surface area, survival property and soft agar growth ability after deletion of TRPV4 gene in the cells with its CRISPR/Cas9 system. With these experiments, we confirmed that TRPV4 is required not only to function as Ca2+ channel but also to maintain its proper cell morphology as a corner stone protein on the cell adhesion junction.

关键词： TRPV4 Ca2+ Ion Channel E-Cadherin Tubulin Soft Agar Growth CRISPR/Cas9 Scissor System

The interaction between Fe65 and Tip60 is regulated by S-nitrosylation on 440 cystein residue of Fe65

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Advances in Biological Chemistry 2011年第3期1卷 109-118页

作者： Eun Jeoung Lee sung hwa shin sunghee Hyun Jaesun Chun Sang Sun Kang 不详

The S-Nitrosylation of protein thiol groups by NO is a widely recognized protein modification. The treat-ment of cells with NOBF4 induces the S-nitrosylation of FE65. In this study, we present evidence showing that FE65 modified by NO (Nitric Oxide) via S-nitrosylation induces functional changes in the protein that inhibits the HAT activity of Tip60. The results of mutational analysis of FE65 demonstrated further that the cysteine residue of FE65 (Cys440) is critical to the process of S-nitrosylation. The mutation of the cysteine residue which completely ablated the S-nitrosylation of FE65 also lost its inhibitory effects on Tip60 HAT activity. Thus, our findings show, for the first time, that the novel regulation mechanism of Tip60 activity may operate via FE65 binding, which is enhanced by S-nitrosylation on the FE65 Cys440 residue. This study describes the interaction between FE65 and Tip60, which is enhanced by a posttransla-tional modification of FE65 (through S-nitrosylation) by NO, promoting the association of the FE65-Tip60 protein complex and inhibiting both the HAT activity of Tip60 and cell death.

关键词： S-Nitrosylation NO(Nitric Oxide) FE65 HAT activity Tip60

Dynamic Changes in Left and Right Cerebral Oxygen Saturation during Selective Cerebral Perfusion in Young Infants

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Congenital Heart Disease 2023年第6期18卷 639-647页

作者： hwa-Young Jang Sang-Jun Beon sung-Hoon Kim In-Kyung Song Won-Jung shin Department of Anesthesiology and Pain Medicine Laboratory for Cardiovascular DynamicsAsan Medical CenterUniversity of Ulsan College of MedicineSeoul05505Korea Department of Physician Education and Training Asan Medical CenterSeoul05505Korea

Objectives:We investigated whether the selective cerebral perfusion(SCP)technique causes differences in changes in cerebral perfusion between both hemispheres in young infants,using cerebral oxygen saturation(ScO2)as an ***,we determined the association between the discrepancy in ScO2 and cerebral perfu-sion pressure during ***:The difference in ScO2 between the left and right cerebral hemispheres(ΔScO2 Rt-Lt)was calculated during clamping of the innominate artery(IA)and during ***:In 25 infants(aged 2 to 78 days),the left and right ScO2 were well maintained(median 63.2%and 60.9%during IA clamping,respectively;64.0%and 65.6%during SCP,respectively).During IA clamping,right and left ScO2 decreased(med-ian-1.4%and-1.0%,respectively).During SCP,rightΔScO2 was higher compared to leftΔScO2(median 1.5%vs.0.6%;p<0.001).Eight patients had a higher rightΔScO2 than leftΔScO2 throughout *** had lowerΔScO2 Rt-Lt during IA clamping(median-3.2%vs.0.0%;p<0.001)and higherΔScO2 Rt-Lt during SCP than others(median 5.0%vs.-0.8%;p<0.001).During and after SCP,the correlation coefﬁcient between rightΔScO2 and change in the mean arterial pressure was higher in patients with a discrepancy than in others(r=0.731 vs.r=0.519;p<0.001).Conclusions:This study suggests that SCP permits adequate bilateral cerebral ***,the unilateral cerebral perfusion technique may cause a difference in cerebral perfusion between both hemispheres in young infants;this may depend on the perfusion pressure.

关键词： Cerebral circulation congenital heart defects monitoring near-infrared spectroscopy

Simulation of water entry of an elastic wedge using the FDS scheme and HCIB method

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Journal of Hydrodynamics 2013年第3期25卷 450-458页

作者： shin Sangmook BAE sung Yong Department of Naval Architecture and Marine Systems Engineering Pukyong National University Busan608-737 Korea

The hydroelasticity of water entry of an elastic wedge is simulated using a code developed using the flux-difference splitting scheme for immiscible and incompressible fluids and the hybrid Cartesian/immersed boundary method. The free surface is regarded as a moving contact discontinuity and is captured without any additional treatment along the interface. Immersed boundary nodes are distributed inside a fluid domain based on the edges that cross an instantaneous body boundary. Dependent variables are reconstructed at each immersed boundary node with the help of an interpolation along a local normal line for providing a boundary condition for a discretized flow problem. A dynamic beam equation is used for modeling the elastic deformation of a wedge. The developed code is validated through comparisons with other experimental and computational results for a free-falling wedge. The effects of the elastic deformation of the wedge on the pressure fields and time histories of the impact force are investigated in relation to the stiffness and density of the structure. Grid independence test is carried out for the computed time history of the force acting on an elastic wedge.

关键词： hydroelasticity free surface capturing non-boundary conforming method dynamic beam equation free falling impactforce

Molecular targeted therapy for hepatocellular carcinoma:Current and future

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World Journal of Gastroenterology 2013年第37期19卷 6144-6155页

作者： Jung Woo shin Young-hwa Chung Department of Internal Medicine University of Ulsan College of Medicine Ulsan University Hospital Department of Internal Medicine University of Ulsan College of MedicineAsan Medical Center

Hepatocellular carcinoma(HCC)is one of the most frequent tumors *** majority of HCC cases occur in patients with chronic liver *** regular surveillance to detect small HCC in these patients,HCC is often diagnosed at an advanced *** HCC is highly resistant to conventional systemic therapies,the prognosis for advanced HCC patients remains *** introduction of sorafenib as the standard systemic therapy has unveiled a new direction for future research regarding HCC ***,given the limited efficacy of the drug,a need exists to look beyond *** molecular targeted agents that inhibit different pathways involved in hepatocarcinogenesis are under various phases of clinical development,and novel targets are being assessed in *** review aims to summarize the efforts to target molecular components of the signaling pathways that are responsible for the development and progression of HCC and to discuss perspectives on the future direction of research.

关键词： Hepatocellular carcinoma Targeted therapy Molecular agents Sorafenib

Evaluation of leaching characteristic and kinetic study of lithium from lithium aluminum silicate glass-ceramics by NaOH

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Journal of Environmental Sciences 2021年第9期33卷 98-110页

作者： Dongseok Lee sung-Ho Joo Dong Ju shin Shun Myung shin Resources Recovery Research Center Korea Institute of Geoscience and Mineral Resources(KIGAM)124 Gwahak-roYuseong-guDaejeon 34132Republic of Korea Department of Resources Recycling University of Science and Technology(UST)217Gajeong-roYuseong-guDaejeon 34113Republic of Korea

The behavior and mechanism of Li leaching from lithium aluminum silicate glass-ceramics which can be used as a secondary source of Li using aqueous NaOH solution was *** Li leaching efficiency is increased with increasing concentration of NaOH, specific surface area, and reaction *** leached under optimum conditions, 2 mol/L NaOH, 53 μm particle undersize, 1:10 solid/liquid ratio, 250 r/min stirring speed, 100℃ reaction temperature, 12 hr, the Li leaching efficiency was approximately 70%.However, when the leaching experiment was performed for 48 hr, the concentration of Li+ ions contained in the leach liquor decreased from 1160 to 236 mg/*** investigate the origin of this phenomenon, the obtained leach residue was analyzed by X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray *** analyses show that zeolite was formed around the lithium aluminum silicate glass-ceramics, which affected the leaching of by adsorbing Li+ *** addition, using the shrinking-core model and the Arrhenius equation, the leaching reaction with NaOH was found to depends on the chemical reaction of the two reactants, with a higher than 41.84 kJ/mol of the activation energy.

关键词： Lithium aluminum silicate glass-ceramics NaOH Lithium Leaching

Effects of ambiguity on innovation strategies

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Financial Innovation 2023年第1期9卷 1813-1839页

作者： hwa‑sung Kim School of Management Kyung Hee University26 Kyungheedae‑RoDongdaemun‑GuSeoul 130‑701Korea

Technological innovations significantly influence individual firms and other innova-tions,such as financial *** future of a firm depends on its innovation investment *** to the literature,innovation investments are affected by *** study examines how ambiguity affects the innovation strategies of *** show that the innovation strategies of ambiguity-averse managers differ from those of ambiguity-neutral *** ambiguity-neutral managers,ambiguity-averse managers consider a broader variety of innovation strategies for a wider range of future innovation arrival *** the profitability of a future innovation,ambiguity-averse managers delay the investment decision until the profit-ability of the innovation is less ***,we examine innovation strategies under various conditions,including the risk of innovation outdatedness,management disputes,and the varying volatility of innovations.

关键词： Technological innovation Ambiguity Innovation strategy