• Title/Summary/Keyword: protein tyrosine phosphatase 1B

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Screening of Medicinal Herbs for Inhibitory Activity against Protein Tyrosine Phosphatase 1B (생약의 Protein Tyrosine Phosphatase 1B 저해활성 검색)

  • Lee, Woo-Jung;Kim, Su-Nam;Yoon, Goo
    • Korean Journal of Pharmacognosy
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    • v.41 no.3
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    • pp.227-231
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    • 2010
  • Protein tyrosine phosphatase 1B (PTP1B) is predicted to be therapeutic target in treatment of type 2 diabetes and obesity. Thus, in order to search for PTP1B inhibitors, we screened the inhibitory activity of PTP1B in the water extracts of 84 medicinal herbs. Among them, the extracts of Pini Folium, Magnoliae Cortex, Artemisiae asiaticae Herba, Schizonepetae Herba, Menthae Herba, Mume Fructus, Cimicifugae Rhizoma, and Amomi Cardamomi Fructus showed relatively significant (58-68%) inhibitory activity against PTP1B. Especially, the methylene chloride fraction of the methanol extract of Menthae Herba (81% inhibition at 30 ${\mu}g$/ml) showed more potent inhibitory activity against PTP1B than others.

Screening of Marine Microbial Extracts for Tyrosine Phosphatase 1B Inhibitors

  • Sohn, Jae-Hak;Park, Sun Jung;Seo, Changon;Chun, Bokyung;Oh, Hyuncheol
    • Journal of Marine Bioscience and Biotechnology
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    • v.2 no.4
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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 $30{\mu}g/mL$.

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Co-Expression of Protein Tyrosine Kinases EGFR-2 and $PDGFR{\beta}$ with Protein Tyrosine Phosphatase 1B in Pichia pastoris

  • Pham, Ngoc Tu;Wang, Yamin;Cai, Menghao;Zhou, Xiangshan;Zhang, Yuanxing
    • Journal of Microbiology and Biotechnology
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    • v.24 no.2
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    • pp.152-159
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    • 2014
  • The regulation of protein tyrosine phosphorylation is mediated by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) and is essential for cellular homeostasis. Co-expression of PTKs with PTPs in Pichia pastoris was used to facilitate the expression of active PTKs by neutralizing their apparent toxicity to cells. In this study, the gene encoding phosphatase PTP1B with or without a blue fluorescent protein or peroxisomal targeting signal 1 was cloned into the expression vector pAG32 to produce four vectors. These vectors were subsequently transformed into P. pastoris GS115. The tyrosine kinases EGFR-2 and $PDGFR{\beta}$ were expressed from vector pPIC3.5K and were fused with a His-tag and green fluorescent protein at the N-terminus. The two plasmids were transformed into P. pastoris with or without PTP1B, resulting in 10 strains. The EGFR-2 and $PDGFR{\beta}$ fusion proteins were purified by $Ni^{2+}$ affinity chromatography. In the recombinant P. pastoris, the PTKs co-expressed with PTP1B exhibited higher kinase catalytic activity than did those expressing the PTKs alone. The highest activities were achieved by targeting the PTKs and PTP1B into peroxisomes. Therefore, the EGFR-2 and $PDGFR{\beta}$ fusion proteins expressed in P. pastoris may be attractive drug screening targets for anticancer therapeutics.

Docking Study of Biflavonoids, Allosteric Inhibitors of Protein Tyrosine Phosphatase 1B

  • Lee, Jee-Young;Jung, Ki-Woong;Woo, Eun-Rhan;Kim, Yang-Mee
    • Bulletin of the Korean Chemical Society
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    • v.29 no.8
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    • pp.1479-1484
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    • 2008
  • Protein tyrosine phosphatase (PTP) 1B is the superfamily of PTPs and a negative regulator of multiple receptor tyrosine kinases (RTKs). Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as a strategy for the treatment of type 2 diabetes and obesity. Recently, it has been reported that amentoflavone, a biflavonoid extracted from Selaginella tamariscina, inhibited PTP1B. In the present study, docking model between amentoflavone and PTP1B was determined using automated docking study. Based on this docking model and the interactions between the known inhibitors and PTP1B, we determined multiple pharmacophore maps which consisted of five features, two hydrogen bonding acceptors, two hydrogen bonding donors, and one lipophilic. Using receptor-oriented pharmacophore-based in silico screening, we searched the biflavonoid database including 40 naturally occurring biflavonoids. From these results, it can be proposed that two biflavonoids, sumaflavone and tetrahydroamentoflavone can be potent allosteric inhibitors, and the linkage at 5',8''-position of two flavones and a hydroxyl group at 4'-position are the critical factors for their allosteric inhibition. This study will be helpful to understand the mechanism of allosteric inhibition of PTP1B by biflavonoids and give insights to develop potent inhibitors of PTP1B.

Protein tyrosine phosphatase PTPN21 acts as a negative regulator of ICAM-1 by dephosphorylating IKKβ in TNF-α-stimulated human keratinocytes

  • Cho, Young-Chang;Kim, Ba Reum;Cho, Sayeon
    • BMB Reports
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    • v.50 no.11
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    • pp.584-589
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    • 2017
  • Intercellular adhesion molecule-1 (ICAM-1), which is induced by tumor necrosis factor (TNF)-${\alpha}$, contributes to the entry of immune cells into the site of inflammation in the skin. Here, we show that protein tyrosine phosphatase non-receptor type 21 (PTPN21) negatively regulates ICAM-1 expression in human keratinocytes. PTPN21 expression was transiently induced after stimulation with TNF-${\alpha}$. When overexpressed, PTPN21 inhibited the expression of ICAM-1 in HaCaT cells but PTPN21 C1108S, a phosphatase activity-inactive mutant, failed to inhibit ICAM-1 expression. Nuclear factor-${\kappa}B$ (NF-${\kappa}B$), a key transcription factor of ICAM-1 gene expression, was inhibited by PTPN21, but not by PTPN21 C1108S. PTPN21 directly dephosphorylated phospho-inhibitor of ${\kappa}B$ ($I{\kappa}B$)-kinase ${\beta}$ ($IKK{\beta}$) at Ser177/181. This dephosphorylation led to the stabilization of $I{\kappa}B{\alpha}$ and inhibition of NF-${\kappa}B$ activity. Taken together, our results suggest that PTPN21 could be a valuable molecular target for regulation of inflammation in the skin by dephosphorylating p-$IKK{\beta}$ and inhibiting NF-${\kappa}B$ signaling.

Revision of Structures of Flavanoids from Scutellaria indica and Their Protein Tyrosine Phosphatase 1B Inhibitory Activity

  • Min, Byung-Sun
    • Natural Product Sciences
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    • v.12 no.4
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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.

Screening of Korean Marine Plants Extracts for Inhibitory Activity on Protein Tyrosine Phosphatase 1B

  • Lee, Hee-Jung;Kim, You-Ah;Lee, Jung-Im;Lee, Burm-Jong;Seo, Young-Wan
    • Journal of Applied Biological Chemistry
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    • v.50 no.2
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    • pp.74-77
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    • 2007
  • Crude extracts of 69 marine organisms (27 salt marsh plants and 42 seaweeds) were screened for the inhibitory activity against the protein tyrosine phosphatase 1B (PTP1) in vitro. The most active extracts were methanol extracts from Derbesia marina (80.6% in inhibitory activity) and Symphycladia latiscula (85.6%) at the concentration of $15{\mu}g/mL$. Methanol extracts of Codium adhaerens and Hisikia fuziformis were moderately inhibitory with 71.2 and 69.1% inhibition, respectively. It was peculiar that only the extracts from seaweeds show inhibitory activity where those from salt marsh plants do not show any significant effect.