• KSBB Journal
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• 제7권4호
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• pp.302-307
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• 1992

protein phosphatase 2A는 bovine brain homogenate의 세포질 fraction에서 얻어졌다. 기질로서 인산화된 histione H1을 이용하여 측정한 phosphatase 의 활성은 dipalmitoyIphophatidylcholine(DPPC) 혹은 phosphatidylserine/DPPC의 혼합물로 구성된 liposome의 존재하에서 저해되었다. Protein phosphatase 2A의 lipid membrane에의 결합은 다중층 지질막의 혼합물 계에서 liposome 의 양이 증가함에 따라서 상등액 중의 phosphatase의 활성이 감소하는 것으로 확인할 수 있었다. 또한 [$^{125}I$]protein phosphatase 2A가 liposome과 동시에 용출되는 것으로도 확인되었다. 그러나 liposome에 대한 protein phosphatase의 친화력은 높지 않았다. 한편, okadaic acid와 liposome은 협동으로 phosphatase의 활성을 감소시켰다. 이것은 okadaic acid가 lipid membrane이나 membrane에 결함한 phosphatase에는 결합하지 않는다는 것을 의미한다. 그러므로 lipid membrane에 의한 protein phosphatase 2A의 활성 저해 효과는 phosphatase 2A와 lipid membrane과의 결합에 의한 것이라고 설명될 수있다.

• Molecules and Cells
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• 제42권7호
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• pp.546-556
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• 2019

Protein phosphatase 4 (PP4) is a crucial protein complex that plays an important role in DNA damage response (DDR), including DNA repair, cell cycle arrest and apoptosis. Despite the significance of PP4, the mechanism by which PP4 is regulated remains to be elucidated. Here, we identified a novel PP4 inhibitor, protein phosphatase 4 inhibitory protein (PP4IP) and elucidated its cellular functions. PP4IP-knockout cells were generated using the CRISPR/Cas9 system, and the phosphorylation status of PP4 substrates (H2AX, KAP1, and RPA2) was analyzed. Then we investigated that how PP4IP affects the cellular functions of PP4 by immunoprecipitation, immunofluorescence, and DNA double-strand break (DSB) repair assays. PP4IP interacts with PP4 complex, which is affected by DNA damage and cell cycle progression and decreases the dephosphorylational activity of PP4. Both overexpression and depletion of PP4IP impairs DSB repairs and sensitizes cells to genotoxic stress, suggesting timely inhibition of PP4 to be indispensable for cells in responding to DNA damage. Our results identify a novel inhibitor of PP4 that inhibits PP4-mediated cellular functions and establish the physiological importance of this regulation. In addition, PP4IP might be developed as potential therapeutic reagents for targeting tumors particularly with high level of PP4C expression.

• Natural Product Sciences
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• 제12권4호
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• pp.205-209
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• 2006

The structures of flavonoids, 2(S)-5,7-dihydroxy-8,2'-dimethoxyflavanone (1), wogonin (2), 2(S)-5,7, 2'-trihydroxy-8-methoxyflavanone (3), and 2(S)-5,2',5'-trihydroxy-7,8-dimethoxyflavanone (4), isolated from Scutellaria indica were revised on the basis of 2D NMR spectroscopy, including to gCOSY, gHSQC, and gHMBC. Compounds 1-4 were tested in vitro protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. Compounds 2 and 4 exhibited weak PTP1B inhibitory activity with $IC_{50}$ values of 208 and $337{\mu}M$, respectively.

• Journal of Applied Biological Chemistry
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• 제50권4호
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• pp.301-303
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• 2007

• Natural Product Sciences
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• 제16권4호
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• pp.239-244
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• 2010

Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin signaling, has served as a potential drug target for the treatment of type 2 diabetes. The MeOH extracts of twenty-nine medicinal plants, traditionally used in Vietnam as anti-diabetes agents, were investigated for PTP1B inhibitory activity in vitro. The results indicated that, most materials showed moderate to strong inhibitory activity with $IC_{50}$ values ranging from $3.4\;{\mu}g/mL$ to $35.1\;{\mu}g/mL$; meanwhile, eleven extracts (37.9%) could demonstrate PTP1B activity with $IC_{50}$ values less than $15.5\;{\mu}g/mL$; sixteen extracts (55.2%) could demonstrate PTP1B activity with $IC_{50}$ values ranging from $15.5\;{\mu}g/mL$ to $35.1\;{\mu}g/mL$. The study may provide a proof, at least in a part, for the ethno-medical use in diabetes disease of these plants.

• 약학회지
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• 제36권2호
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• pp.129-136
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• 1992

The effects of ginseng saponins, gypsophila saponin, sodium dodecyl sulfate(SDS), and Triton X-100 on membrane $K^+-dependent$ phosphatase activity which is lipid dependent and represents dephosphorylation step of the complete Na+, $K^+-ATPase$ reaction were investigated in this study to elucidate whether the effects of ginseng saponins are due to the detergent action, using sarcolemma enriched preparation isolated from dog ventricle. $Na^+$, $K^+-ATPase$ and $K^+-dependent$ phosphatase activities of cardiac sarcolemma were about $143\;{\mu}mol$ Pi/mg protein/hr and $34\;{\mu}mol$ p-nitrophenol/mg protein/hr, respectively. While ginseng saponins (triol>total>diol) inhibited $K^+-dependent$ phosphatase activity, gypsophila saponin, and low dose of SDS($0.4\;{\mu}g/{\mu}g$ protein), and Triton X-100 ($0.6\;{\mu}g/{\mu}g$ protein) increased the enzyme activity, indicating disruptive effect of detergents on membrane barriers. The activating effect of low doses of Triton X-100 on membrane $K^+-dependent$ phosphatase appeared at concentration decreasing light scattering. However, the inhibitory effect of ginseng saponin appeared before a decrease in light scattering. These results suggest that low concentrations of ginseng saponins inhibit the membrane $K^+-dependent$ phosphatase by interacting directly with enzyme before membrane disruption.

• 한국해양바이오학회지
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• 제2권4호
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• pp.230-233
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• 2007

Protein tyrosine phosphatase 1B (PTP1B) acts as a negative regulator of insulin signaling, and selective inhibition of PTP1B has served as a potential drug target for the treatment of type 2 diabetes. As part of our searching for PTP1B inhibitors from natural products, the extracts of marine microorganisms were screened for the inhibitory effects on the activity of protein tyrosine phosphatase 1B (PTP1B). Among the tested 304 extracts, 29 extracts exhibited inhibition rate ranging 40.1 - 83.6 % against PTP1B at the concentration level of $30{\mu}g/mL$.

• 대한화장품학회지
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• 제34권2호
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• pp.109-115
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• 2008

기질 화합물로써 $3{\beta}$-hydroxy-12-oleanen-28-oic acid 유도체들의 치환기($R_1{\sim}R_4$)가 변화함에 따른 protein tyrosine phosphatase(PTP)-1B의 저해활성에 관한 비교 분자장 분석(CoMFA) 모델을 유도하고 정량적으로 검토하였다. 최적의 CoMFA F1 모델은 가장 높은 예측성과 상관성($r^2_{cv.}=0.654$ 및 $r^2_{ncv.}=0.995$)을 나타내었다. 저해활성에 관한 CoMFA장 기여비율(%)의 순서는 입체장(53.0%), 정전기장(36.2%) 및 소수성장(10.8%) 이었다. 등고도 분석 결과로부터 저해활성은 기질 분자 내 $R_4$-치환기에 의존적이었으며 특히 melanin 저해활성이 높은 새로운 화합물(P1 및 P2)이 예측되었다.

• Natural Product Sciences
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• 제14권2호
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• pp.143-146
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• 2008

Protein tyrosine phosphatase 1B (PTP1B) is emerging as a potential therapeutic target for the treatment of type-2 diabetes and obesity. To search for new types of PTP1B inhibitors, we have undertaken in vitro enzyme assay for some anthraquinones and stilbenes isolated from plants. Of the anthraquinones tested, physcion (1), 1-O-methylemodin (2), and emodin (3) showed high activities, with $IC_{50}$ values of 7.6, 7.0, and $3.8{\mu}g/mL$, respectively, while the anthraquinone glycosides, physcion-8-O-${\beta}$-D-glucopyranoside (4) and emodin-8- O-${\beta}$-D-glucopyranoside (5), were less active than their aglycones. All the stilbenens (6 - 15) slightly inhibited PTP1B activity at high concentration of $30{\mu}g/mL$. Our findings suggest that the hypoglycemic effect of anthraquinones may be associated with their PTP1B inhibitory activity.

• Natural Product Sciences
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• 제13권4호
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• pp.311-316
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• 2007

In this study, the twenty-four ethyl acetate extracts of twenty-two medicinal plants, traditionally used in Vietnam as anti-diabetes agents, were investigated for ${\alpha}$-amylase and protein tyrosine phosphatase 1B (PTP1B) enzymes inhibitory activity in vitro. The results indicated that, twelve materials (50.0%) showed moderate to strong inhibitory activity in ${\alpha}$-amylase inhibitory activity with $IC_{50}$ values ranging from 2.5 to $48.8{\mu}g/mL$; meanwhile, ten extracts (41.6%) could demonstrate PTP1B activity with $IC_{50}$ values less than $30.5{\mu}g/mL$. Some plants presented interesting activities against both of ${\alpha}$-amylase and PTP1B enzymes such as Catharanthus roseus, Carthamus tinctorius, Momordica charantia, Gynostemma pentaphyllum, Glycyrrhiza glabra, Smilax glabra, Psidium guajava (leave), and Rehmannia glutinosa. The study may provide a proof, at least in a part, for the ethno-medical use in diabetes disease of these plants.