• Title/Summary/Keyword: signal transduction network

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A Metabolic Pathway Drawing Algorithm for Reducing the Number of Edge Crossings

  • Song Eun-Ha;Kim Min-Kyung;Lee Sang-Ho
    • Genomics & Informatics
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    • v.4 no.3
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    • pp.118-124
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    • 2006
  • For the direct understanding of flow, pathway data are usually represented as directed graphs in biological journals and texts. Databases of metabolic pathways or signal transduction pathways inevitably contain these kinds of graphs to show the flow. KEGG, one of the representative pathway databases, uses the manually drawn figure which can not be easily maintained. Graph layout algorithms are applied for visualizing metabolic pathways in some databases, such as EcoCyc. Although these can express any changes of data in the real time, it exponentially increases the edge crossings according to the increase of nodes. For the understanding of genome scale flow of metabolism, it is very important to reduce the unnecessary edge crossings which exist in the automatic graph layout. We propose a metabolic pathway drawing algorithm for reducing the number of edge crossings by considering the fact that metabolic pathway graph is scale-free network. The experimental results show that the number of edge crossings is reduced about $37{\sim}40%$ by the consideration of scale-free network in contrast with non-considering scale-free network. And also we found that the increase of nodes do not always mean that there is an increase of edge crossings.

WEHI-231 cells are defective in the ligand-induced internalization of B cell antigen receptor

  • Yoon, Sang Soon;Kim, Tae Jin
    • IMMUNE NETWORK
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    • v.1 no.3
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    • pp.196-202
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    • 2001
  • Backgorund: WEHI-231 B cell line is a representative model for $IgM^+$ mature B cells. To understand the signaling differences between mature and immature B cells, we compared the responsiveness of WEHI-231 and Bal 17 B cell lines to BCR cross-linking. Methods: The extents of tyrosine phosphorylation, ligand-induced internalization, and activation-induced cell death upon BCR cross-linking were compared in two cell lines. Results: Despite a higher expression of BCR, cross-linking of BCR on WEHI-231 cell evoked a weaker level of tyrosine phosphorylation and BCR endocytosis than Bal 17 cells. Furthermore, the endocytosed BCR could not enter the lysosomal compartment and stayed as peripheral spots in WEHI-231 cells. Conclusion: WEHI-231 cell showed preferred BCR-mediated signaling pathways leading to a reduced capability of antigen presentation as well as the enhanced apoptosis in comparision with Bal 17 cells. These results might reflect the signaling differences between mature and immature B cells.

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Molecular Mechanisms Governing IL-24 Gene Expression

  • Sahoo, Anupama;Im, Sin-Hyeog
    • IMMUNE NETWORK
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    • v.12 no.1
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    • pp.1-7
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    • 2012
  • Interleukin-24 (IL-24) belongs to the IL-10 family of cytokines and is well known for its tumor suppressor activity. This cytokine is released by both immune and nonimmune cells and acts on non-hematopoietic tissues such as skin, lung and reproductive tissues. Apart from its ubiquitous tumor suppressor function, IL-24 is also known to be involved in the immunopathology of autoimmune diseases like psoriasis and rheumatoid arthritis. Although the cellular sources and functions of IL-24 are being increasingly investigated, the molecular mechanisms of IL-24 gene expression at the levels of signal transduction, epigenetics and transcription factor binding are still unclear. Understanding the specific molecular events that regulate the production of IL-24 will help to answer the remaining questions that are important for the design of new strategies of immune intervention involving IL-24. Herein, we briefly review the signaling pathways and transcription factors that facilitate, induce, or repress production of this cytokine along with the cellular sources and functions of IL-24.

A System To Integrate The Biochemical Network Data Efficiently (생화학적 네트워크 데이터의 효율적인 통합을 위한 시스템)

  • Jung, Tae-Sung;Ahn, Myung-Sang;Cho, Wan-Sup
    • Proceedings of the Korean Information Science Society Conference
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    • 2005.07b
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    • pp.238-240
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    • 2005
  • 유전자의 생물학적 기능을 밝히고 세포 내 상호작용을 이해하는 것은 post-genome era의 가장 중요한 작업 중 하나이다. 세포는 서로 다른 컴포넌트들의 상호작용에 의해 아주 복잡한 네트워크를 구성한다. 생화학적 네트워크에는 metabolic, regulatory, signal transduction과 같은 세포의 프로세스를 포함한다. 이러한 생화학적 네트워크들은 서로 다른 정보체계를 가지고 각기 다른 데이터베이스에 분산되어 저장관리 되고 있다. 따라서 생화학적 네트워크 데이터를 체계적으로 효율적으로 저장, 관리하기 위한 데이터베이스에 대한 필요성이 증대되고 있다. 본 논문에서는 기존의 생화학적 네트워크 데이터베이스의 장.단점을 분석하고 객체지향 방식에 입각한 새로운 생화학적 네트워크 데이터의 통합을 위한 시스템 모델을 제시한다. 제안된 시스템 모델은 생화학적 네트워크 데이터에 대한 생물학전 관계를 자연스럽게 표현할 수 있는 객체지향 모델을 사용하였다. 또한 생화학적 네트워크 모델을 묘사하기 위한 응용프로그램 사이의 데이터 교환의 표준언어인 SBML[2]스키마를 기반으로 하고 있다.

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Mitogen-Activated Protein Kinase Kinase 3 Is Required for Regulation during Dark-Light Transition

  • Lee, Horim
    • Molecules and Cells
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    • v.38 no.7
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    • pp.651-656
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    • 2015
  • Plant growth and development are coordinately orchestrated by environmental cues and phytohormones. Light acts as a key environmental factor for fundamental plant growth and physiology through photosensory phytochromes and underlying molecular mechanisms. Although phytochromes are known to possess serine/threonine protein kinase activities, whether they trigger a signal transduction pathway via an intracellular protein kinase network remains unknown. In analyses of mitogen-activated protein kinase kinase (MAPKK, also called MKK) mutants, the mkk3 mutant has shown both a hypersensitive response in plant hormone gibberellin (GA) and a less sensitive response in red light signaling. Surprisingly, light-induced MAPK activation in wild-type (WT) seedlings and constitutive MAPK phosphorylation in dark-grown mkk3 mutant seedlings have also been found, respectively. Therefore, this study suggests that MKK3 acts in negative regulation in darkness and in light-induced MAPK activation during dark-light transition.

A Study on Development of High-speed Data Optical Transmission ADC for Minimization of Time Delay (지연시간 최소화를 위한 고속 데이터 광 전송용 ADC 개발에 관한 연구)

  • Park, Jong-Dae;Park, Chan-Hong;Park, Byeong-Ho;Ahn, Chang-yeop;Seong, Hyeon-Kyeong
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2014.10a
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    • pp.182-185
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    • 2014
  • In this paper, the ADC performs research and development for high speed data transfers to minimize the optical delay. Have more $6{\mu}s$ delay in the data signal converting optical repeater transmission system existing there has been a limit on the high-speed data transmission, and signal conversion. The need to develop a new technique to reduce the delay in time within $2{\mu}s$ data signal converted by using this direct conversion system. It is desired the development of the core technologies necessary for the signal transduction component, such as mobile communications LTE, LTE advanced service transport network is established, the delay time $3{\mu}s$ technology for reducing the delay time in the signal converting a revolutionary step is applied in this paper we have developed an ADC.

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The Human PTK6 Interacts with a 23-kDa Tyrosine-Phosphorylated Protein and is localized in Cytoplasm in Breast Carcinoma T-47D Cells

  • Bae, Joon-Seol;Lee, Seung-Thek
    • BMB Reports
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    • v.34 no.1
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    • pp.33-38
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    • 2001
  • The human PTK6 (also known as Brk) polypeptide, which is deduced from its full-length cDNA, represents a non-receptor protein tyrosine kinase (PTK). It contains SH3, SH2, and tyrosine kinase catalytic domains that are closely related to Src family members. We generated an antihuman PTK6 antibody by immunizing rabbits with a PTK6-specific oligopeptide conjugated to BSA, which corresponds to 11 amino acid residues near the C-terminus. An immunoblot analysis with the antibody detected an expected 52-kDa band in various mammalian transformed cell lines. Immunoprecipitation and immunoblot analyses demonstrated that PTK6 is phosphorylated on the tyrosine residues) and interacts with approximately a 23-kDa tyrosine-phosphorylated polypeptide (most likely a substrate of PTK6) in breast carcinoma T-47D cells. An immunofluorescence analysis demonstrated that PTK6 is localized throughout the cytoplasm of T-47D cells. These results support a possible role for PTK6 in the intracellular signal transduction through tyrosine phosphorylation.

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Systems-level mechanisms of action of Panax ginseng: a network pharmacological approach

  • Park, Sa-Yoon;Park, Ji-Hun;Kim, Hyo-Su;Lee, Choong-Yeol;Lee, Hae-Jeung;Kang, Ki Sung;Kim, Chang-Eop
    • Journal of Ginseng Research
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    • v.42 no.1
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    • pp.98-106
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    • 2018
  • Panax ginseng has been used since ancient times based on the traditional Asian medicine theory and clinical experiences, and currently, is one of the most popular herbs in the world. To date, most of the studies concerning P. ginseng have focused on specific mechanisms of action of individual constituents. However, in spite of many studies on the molecular mechanisms of P. ginseng, it still remains unclear how multiple active ingredients of P. ginseng interact with multiple targets simultaneously, giving the multidimensional effects on various conditions and diseases. In order to decipher the systems-level mechanism of multiple ingredients of P. ginseng, a novel approach is needed beyond conventional reductive analysis. We aim to review the systems-level mechanism of P. ginseng by adopting novel analytical framework-network pharmacology. Here, we constructed a compound-target network of P. ginseng using experimentally validated and machine learning-based prediction results. The targets of the network were analyzed in terms of related biological process, pathways, and diseases. The majority of targets were found to be related with primary metabolic process, signal transduction, nitrogen compound metabolic process, blood circulation, immune system process, cell-cell signaling, biosynthetic process, and neurological system process. In pathway enrichment analysis of targets, mainly the terms related with neural activity showed significant enrichment and formed a cluster. Finally, relative degrees analysis for the target-disease association of P. ginseng revealed several categories of related diseases, including respiratory, psychiatric, and cardiovascular diseases.

Regulation of Interleukin-17 Production in Patients with Rheumatoid Arthritis by Phosphoinositide 3-kinase (PI3K)/Akt and Nuclear Factor KappaB (NF-κB) Dependent Signal Transduction Pathway (류마티스 관절염 환자의 말초혈액 단핵세포에서 Phosphoinositide 3-Kinase (PI3K)/Akt와 Nuclear Factor KappaB (NF-κB) 신호전달을 통한 IL-17 생성조절)

  • Kim, Kyoung-Woon;Cho, Mi-La;Lee, Sang-Heon;Min, So-Youn;Park, Mi Kyung;Park, Sung-Hwan;Jue, Dae-Myung;Kim, Ho-Youn
    • IMMUNE NETWORK
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    • v.3 no.4
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    • pp.310-319
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    • 2003
  • Inflammatory mediators has been recognized as an important role in the pathogenesis of rheumatoid arthritis (RA). IL-17 is increasingly recognized as an important regulator of immune and inflammatory responses, including induction of proinflammatory cytokines and osteoclastic bone resorption. Evidence of the expression and proinflammatory activity of IL-17 has been demonstrated in RA synovium and in animal models of RA. However, the signaling pathways that regulate IL-17 production remain unknown. In the present study, we investigated the role of the phosphatidylinositol 3 kinase (PI3K)-Akt pathway in the regulation of IL-17 production in RA. PBMC were separated from RA (n=24) patients, and stimulated with various agents (anti CD3, anti CD28, PHA, ConA, IL-15). IL-17 levels were determined by sandwich ELISA and RT-PCR. The production of IL-17 was significantly increased in cells treated with anti-CD3 antibody, PHA, IL-15 or MCP-1 (P<0.05). ConA also strongly induced IL-17 production (P<0.001), whereas TNF-alpha, IL-1beta, IL-18 or TGF-beta did not. IL-17 was detected in the PBMC of patients with osteoarthritis (OA) but their expression levels were much lower than those of RA PBMC. Anti-CD3 antibody activated the PI3K-Akt pathway and activation of the PI3K-Akt pathway resulted in a pronounced augmentation of nuclear factor kappaB ($NF-{\kappa}B$). IL-17 production by activated PBMC in RA is completely or partially blocked in the presence of $NF-{\kappa}B$ inhibitor PDTC and PI3K-Akt inhibitor, wortmannin and LY294002, respectively. Whereas the inhibition of AP-1 and extracellular signal-regulated kinase (ERK)1/2 did not affect IL-17 production. These results provide new insight into that PI3K/Akt and $NF-{\kappa}B$ dependent signal transduction pathway could be involved in the overproduction of key inflammatory cytokine, IL-17 in rheumatoid arthritis.

Regulation of Inflammatory Repertoires and NF-${\kappa}B$ Signal Transduction by DDB, an Active Compound from Schizandra Chinensis Baillon (오미자 활성성분 DDB의 NF-${\kappa}B$ 신호 전달 및 염증물질 발현 조절)

  • Joo, Seong-Soo;Yoo, Yeong-Min;Won, Tae-Joon;Kim, Min-Jung;Lee, Seon-Goo;Hwang, Kwang-Woo;Lee, Do-Ik
    • IMMUNE NETWORK
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    • v.6 no.1
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    • pp.27-32
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    • 2006
  • Background: Chronic inflammation in the brain has known to be associated with the development of a various neurological diseases including dementia. In general, the characteristic of neuro-inflammation is the activated microglia over the brain where the pathogenesis occurs. Pro-inflammatory repertoires, interleukin-1${\beta}$ (IL-1${\beta}$) and nitric oxide (NO), are the main causes of neuro-degenerative disease, particularly in Alzheimer's disease (AD) which is caused by neuronal destruction. Those pro-inflammatory repertoires may lead the brain to chronic inflammatory status, and thus we hypothesized that chronic inflammation would be inhibited when pro-inflammatory repertoires are to be well controlled by inactivating the signal transduction associated with inflammation. Methods: In the present study, we examined whether biphenyl dimethyl dicarboxylate (DDB), an active compound from Schizandra chinensis Baillon, inhibits the NO production by a direct method using Griess reagent and by RT-PCR in the gene expression of inducible nitric oxide synthase (iNOS) and IL-1${\beta}$. Western blots were also used for the analysis of NF-${\kappa}B$ and I${\kappa}B$. Results: In the study, we found that DDB effectively inhibited IL-1${\beta}$ as well as NO production in BV-2 microglial cell, and the translocation of NF-${\kappa}B$ was comparably inhibited in the presence of DDB comparing those to the positive control, lipopolysaccharide. Conclusion: The data suggested that the DDB from Schizandra chinensis Baillon may play an effective role in inhibiting the pro-inflammatory repertoires which may cause neurodegeneration and the results imply that the compound suppresses a cue signal of the microglial activation which can induce the brain pathogenesis such as Alzheimer's disease.