• Title/Summary/Keyword: Regulator Activity

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Protein tyrosine phosphatase PTPRT as a regulator of synaptic formation and neuronal development

  • Lee, Jae-Ran
    • BMB Reports
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    • v.48 no.5
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    • pp.249-255
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    • 2015
  • PTPRT/RPTPρ is the most recently isolated member of the type IIB receptor-type protein tyrosine phosphatase family and its expression is restricted to the nervous system. PTPRT plays a critical role in regulation of synaptic formation and neuronal development. When PTPRT was overexpressed in hippocampal neurons, synaptic formation and dendritic arborization were induced. On the other hand, knockdown of PTPRT decreased neuronal transmission and attenuated neuronal development. PTPRT strengthened neuronal synapses by forming homophilic trans dimers with each other and heterophilic cis complexes with neuronal adhesion molecules. Fyn tyrosine kinase regulated PTPRT activity through phosphorylation of tyrosine 912 within the membrane-proximal catalytic domain of PTPRT. Phosphorylation induced homophilic cis dimerization of PTPRT and resulted in the inhibition of phosphatase activity. BCR-Rac1 GAP and Syntaxin-binding protein were found as new endogenous substrates of PTPRT in rat brain. PTPRT induced polymerization of actin cytoskeleton that determined the morphologies of dendrites and spines by inhibiting BCR-Rac1 GAP activity. Additionally, PTPRT appeared to regulate neurotransmitter release through reinforcement of interactions between Syntaxin-binding protein and Syntaxin, a SNARE protein. In conclusion, PTPRT regulates synaptic function and neuronal development through interactions with neuronal adhesion molecules and the dephosphorylation of synaptic molecules. [BMB Reports 2015; 48(5): 249-255]

A Role of Plasminogen Activators in Animal Reproductive Cells and Organs

  • HwangBo, Yong;Cheong, Hee-Tae;Yang, Boo-Keun;Park, Choon-Keun
    • Reproductive and Developmental Biology
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    • v.38 no.2
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    • pp.63-70
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    • 2014
  • Plasminogen activators (PAs) are serine proteases that convert plasminogen to plasmin. Two type of PAs are urokinase-type PA (uPA) and tissue-type PA (tPA). Plasminogen is present in most extracellular fluids. PAs play in various reproductive processes including implantation, ovulation and fertilization. In the spermatozoa, PAs and PAIs play a role in sperm motility and fertilization. PAs in the sertoli cell are stimulated spermatozoa maturation and sperm activation through the phospholipase A2. The oocyte maturation is the process for fertilization and implantation. PAs in cumulus-oocyte complexes (COCs) are related to oocyte maturation by protein kinase A and C. In the ovulatory process, PAs activity are changed and it are related to reducing the tensile strength of ovarian follicle wall. The uterine environment is important for reproduction and the uterus undergo tissue remodeling. In the uterus and oviduct of mammals, expression and activity of PAs are changed during estrous cycle. Thus, expression and activity of PAs are concerned to many reproductive functions. Therefore, PAs seem to important factor of regulator in reproductive events.

Upregulation of NF-κB upon differentiation of mouse embryonic stem cells

  • Kim, Young-Eun;Kang, Ho-Bum;Park, Jeong-A;Nam, Ki-Hoan;Kwon, Hyung-Joo;Lee, Young-Hee
    • BMB Reports
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    • v.41 no.10
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    • pp.705-709
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    • 2008
  • NF-${\kappa}B$ is a transcriptional regulator involved in many biological processes including proliferation, survival, and differentiation. Recently, we reported that expression and activity of NF-${\kappa}B$ is comparatively low in undifferentiated human embryonic stem (ES) cells, but increases during differentiation. Here, we found a lower expression of NF-${\kappa}B$ p65 protein in mouse ES cells when compared with mouse embryonic fibroblast cells. Protein levels of NF-${\kappa}B$ p65 and relB were clearly enhanced during retinoic acid-induced differentiation. Furthermore, increased DNA binding activity of NF-${\kappa}B$ in response to TNF-$\alpha$, an agonist of NF-${\kappa}B$ signaling, was seen in differentiated but not undifferentiated mouse ES cells. Taken together with our previous data in human ES cells, it is likely that NF-${\kappa}B$ expression and activity of the NF-${\kappa}B$ signaling pathway is comparatively low in undifferentiated ES cells, but increases during differentiation of ES cells in general.

Screening of the Inhibitory Activity of Medicinal Plants against Protein Tyrosine Phosphatase 1B (생약의 Protein Tyrosine Phosphatase 1B (PTP1B) 저해활성 검색)

  • Hong, Jung-Hyun;Lee, Myung-Sun;Bae, Eun-Young;Kim, Young-Ho;Oh, Hyun-Cheol;Oh, Won-Keun;Kim, Bo-Yeon;Ahn, Jong-Seog
    • Korean Journal of Pharmacognosy
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    • v.35 no.1 s.136
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    • pp.16-21
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    • 2004
  • Protein tyrosine phosphatase 1B(PTP1B) is thought to be a negative regulator in insulin signal-transduction pathway. Insulin-resistance by the activation of PTP1B is a hallmark of both type 2 diabetes and obesity. Thus, the compounds inhibiting PTP1B can improve insulin resistance and can be effective in treating type 2 diabetes and obesity. The methanol extracts of 160 herbal medicines were screened for the inhibitory activity against PTP1B. Among the tested extracts, methanol extracts of Amsonia elliptica, Areca catechu, Benincasa hispida, Morus alba, Salvia miltiorrhiza, Siegesbeckia orientalis, and Trichosanthes kirilowii showed relatively strong inhibitory activity against PTP1B.

Antaroide, a Novel Natural Nine-Membered Macrolide, Inhibits Melanin Biosynthesis in B16F10 Murine Melanoma Cells

  • Ryu, Min-Ji;Baek, Eun-Ki;Kim, Soyeon;Seong, Chi Nam;Yang, Inho;Lim, Kyung-Min;Nam, Sang-Jip
    • Biomolecules & Therapeutics
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    • v.29 no.1
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    • pp.98-103
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    • 2021
  • The demand for natural substances with anti-melanogenic activity is increasing due to the recent interest in skin whitening. Intensive investigation on the culture broth of Streptomyces sp. SCO-736, a marine bacterium from the Antarctica coast, has led to the isolation of a new natural product named antaroide (1). The chemical structure was established through the interpretation of MS, UV, and NMR spectroscopic data. Antaroide is a nine-membered macrolide with lactone and lactam moieties. To investigate its applicability in skin whitening cosmetics, its anti-melanogenic activity in B16F10 murine melanoma cells was examined. As a result, antaroide displayed strong inhibitory activities against melanin synthesis and also attenuated the dendrite formation induced by the α-melanocyte stimulating hormone (α-MSH). Antaroide suppressed the mRNA expression of the melanogenic enzymes such as tyrosinase, TRP-1 and TRP-2. This suggests that it may serve as a transcriptional regulator of melanogenesis. Collectively, the discovery of this novel natural nine-membered macrolide and its anti-melanogenic activity could give new insights for the development of skin whitening agents.

Inhibitory Effects of Epigallocatechin-3-Gallate on Microsomal Cyclooxygenase-1 Activity in Platelets

  • Lee, Dong-Ha;Kim, Yun-Jung;Kim, Hyun-Hong;Cho, Hyun-Jeong;Ryu, Jin-Hyeob;Rhee, Man Hee;Park, Hwa-Jin
    • Biomolecules & Therapeutics
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    • v.21 no.1
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    • pp.54-59
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    • 2013
  • In this study, we investigated the effect of (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea catechins from green tea leaves, on activities of cyclooxygenase (COX)-1 and thromboxane synthase (TXAS), thromboxane $A_2$ ($TXA_2$) production associated microsomal enzymes. EGCG inhibited COX-1 activity to 96.9%, and TXAS activity to 20% in platelet microsomal fraction having cytochrome c reductase (an endoplasmic reticulum marker enzyme) activity and expressing COX-1 (70 kDa) and TXAS (58 kDa) proteins. The inhibitory ratio of COX-1 to TXAS by EGCG was 4.8. These results mean that EGCG has a stronger selectivity in COX-1 inhibition than TXAS inhibition. In special, a nonsteroid anti-inflammatory drug aspirin, a COX-1 inhibitor, inhibited COX-1 activity by 11.3% at the same concentration ($50{\mu}M$) as EGCG that inhibited COX-1 activity to 96.9% as compared with that of control. This suggests that EGCG has a stronger effect than that of aspirin on inhibition of COX-1 activity. Accordingly, we demonstrate that EGCG might be used as a crucial tool for a strong negative regulator of COX-1/$TXA_2$ signaling pathway to inhibit thrombotic disease-associated platelet aggregation.

Identification of Genes for Biosynthesis of Antibacterial Compound from Pseudomonas fluorescens Bl6, and Its Activity Against Ralstonia solanacearum

  • Kim, Jin-Woo;Kim, Jung-Gun;Park, Byoung-Keun;Choi, Ok-Hee;Park, Chang-Seuk;Hwang, In-Gyu
    • Journal of Microbiology and Biotechnology
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    • v.13 no.2
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    • pp.292-300
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    • 2003
  • Pseudomonas fluorescens B16 is a plant glowth-prornoting rhizobacterium, which produces an antibacterial compound that is effective against plant root pathogens, such as Agrobacrerium tumefaciens and Raistonia solanacearum. We mutagenized the strain B16 with Omegon-Km and isolated six antibacterial-activity-deficient mutants. Two cosmid clones that hybridized with the mutant clones also were isolated from a genomic library of tile parent strain. Using deletion and complementation analyses, it was found that the biosynthesis genes resided in a 4.3-kb SalI-NarI fragment. When a plasmid clone carrying the fragment was introduced into P. fluorescens strain 1855.344, which does not exhibit any antibacterial activity, the transconjugants exhibited antibacterial activity, indicating that the plasmid clone carried all the genes essential for production of the antibacterial compound. DNA sequence analysis of the fragment identified four putative open reading frames (ORFs): orf1 through orf4 The deduced amino acid sequences of ORF1, ORF2, and ORF4 were similar to cystathionine gamma lyase, pyruvate formate-lyase activating enzyme, and transcriptional regulator, respectively, yet the amino acid sequence of ORF3 showed no similarities to any known proteins. It was also demonstrated that the antibacterial activity was responsible for biological control of the bacterial wilt caused by R. solanacearum.

Vertical Shoot Growth of Korean Lawngrass (Zoysia japonica Steud.) Influenced by Trinexapac-ethyl, Amidochlor, and Mefluidide (Trinexapac-ethyl, Amidochlor 및 Mefluidide가 들잔디 직립생장에 미치는 효과)

  • Kim, Kyoung-Nam;Kim, Yong-Seon
    • Horticultural Science & Technology
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    • v.17 no.5
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    • pp.572-577
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    • 1999
  • Research was initiated to evaluate plant growth regulator effects on the vertical shoot growth of Korean lawngrass and to determine desirable growth regulator and its rate. The experiments were conducted twice at different sites in 1995. All the tested growth regulators inhibited the growth, but the inhibition period was variable among the product in Experiments I and II. During the first week after treatment, there was approximately 10 to 20% growth reduction in most of the treated plots. In the amidochlor-treated plots, growth suppression was effective for 3 to 4 weeks at low to medium rates ($0.60mL{\cdot}m^{-2}$). A Type II growth regulator, trinexapac-ethyl exceeding the medium rate of $0.08mL{\cdot}m^{-2}$ consistently tended to suppress vertical shoot growth for 8 weeks, being above 35% reduction in both experiments. In the plots applied with mefluidide, growth suppression appeared with foliar discoloration 3 or 4 days earlier than the other growth regulators and continued to work till the 8 weeks after treatment. Suppression intensity on vertical shoot growth increased with time after treatment up to a certain period of time, depending on growth regulators. Generally, the higher the application rate, the greater the suppression intensity. Seasonal variation of activity and effectiveness of growth regulators was observed, resulting in lower suppression intensity in July than in June. It is expected to reduce mowing requirements by 30 to up to 60% for a certain period with a specific growth regulator. In low to medium maintenance of Korean lawngrass turf, a long-term suppression may be more effectively accomplished with trinexapac-ethyl rather than mefluidide and amidochlor in terms of vertical shoot growth inhibition. Therefore, turf managers will need to select proper growth regulator and determine optimum rate of application for turfgrass management, based on a defined period of mowing reduction.

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Identification of Amino Acids Involved in the Sensory Function of the PrrB Histidine Kinase by Site-directed Mutagenesis (Site-directed mutagenesis에 의한 PrrB histidine kinase의 신호인지 기능에 관련된 아미노산의 발굴)

  • Kim Yong-Jin;Ko In-Jeong;Oh Jeong-Il
    • Journal of Life Science
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    • v.16 no.3 s.76
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    • pp.485-492
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    • 2006
  • The PrrBA two-component system is one of the major regulatory systems that control expression of photosynthesis genes in response to changes in oxygen tension in the anoxygenic photosynthetic bacterium, Rhodobacter sphaeroides. The system consists of the PrrB histidine kinase and the PrrA response regulator. The N-terminal transmembrane domain of PrrB serves as a signal-sensing domain and comprises six transmembrane helices forming three periplasmic loops and two cytoplasmic loops. The $3^{rd}$ and $4^{th}$ transmembrane helices and the $2^{nd}$ periplasmic loop were suggested to play a crucial role in redox-sensory function. In this study we demonstrated that mutations of Asp-90, Gln-93, Leu-94, Leu-98, and Asn-106 in the $2^{nd}$ periplasmic loop and its neighboring region led to severe defects in PrrB sensory function, indicating that these amino acids might be related to the redox-sensing function of PrrB. The mutant forms (D90E, D90N, and D90A) of PrrB were heterologously overexpressed in Escherichia coli, purified by means of affinity chromatography and their autokinase activities were comparatively assessed. The D90N form of PrrB was shown to possess higher autokinase activity than the wild-type form of PrrB, whereas the D90E form of PrrB displayed lower autokinase activity than the wild-type form of PrrB. The D90A mutation led to the loss of PrrB autokinase activity.

EFFECT OF PDGF AND $TGF-{\beta}1$ ON CELL ACTIVITY OF HUMAN GINGIVAL FIBROBLAST AND PERIODONTAL LIGAM ENT CELL IN VITRO (PDGF와 $TGF-{\beta}1$이 배양 인체 치은 섬유모세포와 치주인대세포의 활성에 미치는 영향)

  • Chung, Soon-Kyu;Nam, Goong-Hyuk;Shin, Hyung-Shik
    • Journal of Periodontal and Implant Science
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    • v.25 no.1
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    • pp.133-145
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    • 1995
  • The migration and proliferation of periodontal ligament cells are desired goal of periodontal regeneration therapy. PDGF and $TGF-{\beta}1$ are well known to regulate the cell activity of mesenchymal origin cell. The purpose of this study was to determine the effects of these growth factors on human gingival fibroblast and periodontal ligament cell actvity, and to identify the regulatory effect of $TGF-{\beta}1$ on the response to PDGF by MIT assay. Human gingival fibroblast and periodontal ligament cells were cultured from extracted teeth for non-periodontal reason. Cultured human gingival fibroblast and periodontal ligament cells in vitro were treated with polyperpetide growth factor PDGF and $TGF-{\beta}1$ in both a dose and time - dependent manner. Cell morphology were determined by inverted microscope and cell acitivity were determined by MIT assay. The result of this study demonstrated that PDGF and $TGF-{\beta}1$ were not changed the morphology of these cell compared with control group. PDGF or $TGF-{\beta}1$ increased cell activity of periodontal ligament cell in dose and time dependent manner but gingival fibroblast were decreased to the level of control group at third day. Additionally, incubation with $TGF-{\beta}1$ addition to PDGF resulted in a enhanced cell activity of PDGF. Therefore, cell acitivty of gingival fibroblast were not changed compared with control group. This stiudy demonstrates that PDGF and $TGF-{\beta}1$ are major mitogens for human periodontal ligament cell in vitro, and $TGF-{\beta}1$ is a regulator of cell activity to PDGF in human gingival fibroblast and periodontal ligament cell.

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