• Title/Summary/Keyword: Syndecan-3

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Solution Structure of the Cytoplasmic Domain of Syndecan-3 by Two-dimensional NMR Spectroscopy

  • Yeo, In-Young;Koo, Bon-Kyung;Oh, Eok-Soo;Han, Inn-Oc;Lee, Weon-Tae
    • Bulletin of the Korean Chemical Society
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    • v.29 no.5
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    • pp.1013-1017
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    • 2008
  • Syndecan-3 is a cell-surface heparan sulfate proteoglycan, which performs a variety of functions during cell adhension process. It is also a coreceptor for growth factor, mediating cell-cell and cell-matrix interaction. Syndecan-3 contains a cytoplasmic domain potentially associated with the cytoskeleton. Syndecan-3 is specifically expressed in neuron cell and has related to neuron cell differentiation and development of actin filament in cell migration. Syndecans each have a unique, central, and variable (V) region in their cytoplasmic domains. And that region of syndecan-3 may modulate the interactions of the conserved C1 regions of the cytoplasmic domains by tyrosine phosphorylation. Cytoplasmic domain of syndecan-3 has been synthesized for NMR structural studies. The solution structure of syndecan-3 cytoplasmic domain has been determined by two-dimensional NMR spectroscopy and simulated-annealing calculation. The cytoplasmic domain of the syndecan proteins has a tendency to form a dimmer conformation with a central cavity, however, that of syndecan-3 demonstrated a monomer conformation with a flexible region near C-terminus. The structural information might add knowledge about the structure-function relationships among syndecan proteins.

Syndecan as a Messenger to Link Diabetes and Cancer

  • Kim, Sung-Jin;Raman, Os Sethu
    • Biomolecules & Therapeutics
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    • v.19 no.3
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    • pp.267-273
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    • 2011
  • Syndecans are membrane-anchored proteoglycans and implicated in the pathogenesis of cancer progression and metastasis. Syndecans also play important roles in interacting with growth factors, extracellular matrix and other cell surface molecules such as IGF-1 receptor. In the present review, we discuss about the syndecan structure, their role in signaling with other receptors, in addition to its general biology. The emerging roles of syndecans in the pathophysiology of human diseases, especially insulin resistance, diabetes and cancer is discussed.

Ubiquitin Fusion System for Recombinant Peptide Expression and Purification: Application to the Cytoplasmic Domain of Syndecan-4

  • Chae, Young-Kee;Lee, Ha-Yan;Lee, Weon-Tae
    • Bulletin of the Korean Chemical Society
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    • v.28 no.9
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    • pp.1549-1552
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    • 2007
  • The cytoplasmic domain of syndecan-4, a type I transmembrane heparan sulfate proteoglycan, was overexpressed as a fused form with the ubiquitin molecule in Escherichia coli, and the fusion protein was purified using immobilized metal affinity chromatography (IMAC). The cytoplasmic domain was released from its fusion partner by using yeast ubiquitin hydrolase (YUH), and subsequently purified by reverse phase chromatography. The integrity of the resulting peptide fragment was checked by MALDI-TOF and NMR spectroscopy. The yield of the peptide was 3.0-1.5 mg per liter in LB or minimal medium, respectively. The recombinant expression and purification of this domain will enable us its structural and functional studies using multidimensional NMR spectroscopy.

Structure Determination of Syndecan-4 Transmembrane Domain using PISA Wheel Pattern and Molecular Dynamics simulation

  • Choi, Sung-Sub;Jeong, Ji-Ho;Kim, Ji-Sun;Kim, Yongae
    • Journal of the Korean Magnetic Resonance Society
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    • v.18 no.2
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    • pp.58-62
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    • 2014
  • Human transmembrane proteins (hTMPs) are closely related to transport, channel formation, signaling, cell to cell interaction, so they are the crucial target of modern medicinal drugs. In order to study the structure and function of these hTMPs, it is important to prepare reasonable amounts of proteins. However, their preparation is seriously difficult and time-consuming due to insufficient yields and low solubility of hTMPs. We tried to produce large amounts of Syndecan-4 transmembrane domain (Syd4-TM) that is related to the healing wounds and tumor for a long time. In this study, we performed the structure determination of Syd4-TM combining the Polarity Index at Slanted Angle (PISA) wheel pattern analysis based on $^{15}N-^1H$ 2D SAMPI-4 solid-state NMR of expressed Syd4-TM and Molecular Dynamics (MD) simulation using Discovery Studio 3.1.

Inhibitory effects of antithrombin on the expression of secretory group IIA phospholipase A2 in endothelial cells

  • Kim, Tae-Hoon;Bae, Jong-Sup
    • BMB Reports
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    • v.43 no.9
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    • pp.604-608
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    • 2010
  • Tumor necrosis factor-$\alpha$ (TNF-$\alpha$) mediates proinflammatory responses in primary human umbilical vein endothelial cells (HUVECs), and it upregulates the expression of secretory group IIA phospholipase $A_2$ ($sPLA_2$-IIA). $sPLA_2$-IIA plays a pivotal role in inflammation, and antithrombin (AT) possesses properties that are beneficial to endothelial cells. Therefore, we investigated the effects of AT on the expression of $sPLA_2$-IIA in TNF-$\alpha$-stimulated HUVECs. TNF-$\alpha$ potently upregulated the expression of $sPLA_2$-IIA, and prior treatment of cells with AT inhibited the expression of $sPLA_2$-IIA in HUVECs. Also, antibodies or siRNA for syndecan-4 blocked the protective effect of AT. Furthermore, PI3-kinase and the AKT pathway are significantly involved in the AT-mediated inhibition of the expression of $sPLA_2$-IIA. These results show that AT effectively suppresses the upregulated $sPLA_2$-IIA expression, which might contribute to the cytoprotective effects of AT in the treatment of severe inflammatory diseases.

Fine Needle Aspiration Cytology of the Plasmablastic Lymphoma in Human Immunodeficiency Virus (HIV) Negative Patient - A Case Report - (HIV 음성 환자에서 형질모세포종의 세침흡인 세포소견 - 1예 보고 -)

  • Lee, Hyang-Im;Koo, Hyun-Ryung;Han, Eun-Mee;Gong, Gyung-Yub;Suh, Chul-Won;Ryu, Min-Hee;Kang, Yoon-Goo;Park, Chan-Jeong;Huh, Joo-Ryung
    • The Korean Journal of Cytopathology
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    • v.16 no.1
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    • pp.47-51
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    • 2005
  • Plasmablastic lymphoma (PBL) is a recently described aggressive B-cell neoplasm, which usually manifests as a localized disease of the oral mucosa in individuals infected with human immunodeficiency virus (HIV). Recently we encountered a case of plasmablastic lymphoma manifesting in the left maxillary sinus and cervical lymph node of a previously healthy HIV-negative man, 48 years of age. we conducted a fine-needle aspiration smear of the cervical lymph node, and this was found to be highly cellular with numerous large cells exhibiting eccentrically positioned nuclei, prominent nucleoli, and moderate quantities of basophilic cytoplasm. A biopsy of the mass in the maxillary sinus evidenced diffuse growth of similar plasmablastic cells. These tumor cells were negative for the leukocyte common antigens, CD20, CD3, CD30, and EMA. However, the cells tested positive for CD79a and CD138/syndecan-1. The tumor cells also exhibited L-light-chain restriction. The Ki-67 proliferation index was measured at almost 100%. The patient was diagnosed with plasmablastic lymphoma. After three cycles of combination chemotherapy and radiotherapy, the patient went into complete remission, and currently remains in this state.

Low-Level Expression of CD138 Marks Naturally Arising Anergic B Cells

  • Sujin Lee;Jeong In Yang;Joo Hee Lee;Hyun Woo Lee;Tae Jin Kim
    • IMMUNE NETWORK
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    • v.22 no.6
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    • pp.50.1-50.19
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    • 2022
  • Autoreactive B cells are not entirely deleted, but some remain as immunocompetent or anergic B cells. Although the persistence of autoreactive B cells as anergic cells has been shown in transgenic mouse models with the expression of B cell receptor (BCR) reactive to engineered self-antigen, the characterization of naturally occurring anergic B cells is important to identify them and understand their contribution to immune regulation or autoimmune diseases. We report here that a low-level expression of CD138 in the splenic B cells marks naturally arising anergic B cells, not plasma cells. The CD138int B cells consisted of IgMlowIgDhigh follicular (FO) B cells and transitional 3 B cells in homeostatic conditions. The CD138int FO B cells showed an anergic gene expression profile shared with that of monoclonal anergic B cells expressing engineered BCRs and the gene expression profile was different from those of plasma cells, age-associated B cells, or germinal center B cells. The anergic state of the CD138int FO B cells was confirmed by attenuated Ca2+ response and failure to upregulate CD69 upon BCR engagement with anti-IgM, anti-IgD, anti-Igκ, or anti-IgG. The BCR repertoire of the CD138int FO B cells was distinct from that of the CD138- FO B cells and included some class-switched B cells with low-level somatic mutations. These findings demonstrate the presence of polyclonal anergic B cells in the normal mice that are characterized by low-level expression of CD138, IgM downregulation, reduced Ca2+ and CD69 responses upon BCR engagement, and distinct BCR repertoire.

The Effects of Echinacea Extract on the Gene Expression of Monocytes and Monocyte-derived Dendritic Cells (Echinacea 추출물이 단구와 단구유래 수지상세포의 유전자발현에 미치는 효과)

  • Park, Jun Eun;Choi, Kang Duk;Kim, Sung Hwan;Hahm, Dae-Hyun;Seo, Jong Jin
    • Clinical and Experimental Pediatrics
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    • v.48 no.7
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    • pp.779-788
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    • 2005
  • Purpose : Echinacea, a traditional plant medicine has been used as immune-stimulant. Recent studies have revealed that extract of Echinacea has immunostimulatory effects on human blood mononuclear cells. This study was designed for the purpose of screening the genes associated with immunologic effects of Echinacea on monocytes and dendritic cells using a cDNA microarray chip. Methods : $CD14^+$ monocyte cells were cultured for one day with Echinacea extract(final concentration : $50{\mu}g/mL$) in experiment 1, but were cultured without Echinacea in experiment 2. The gene expression of these cultured monocytes was analyzed using the cDNA microarray chip. Dendritic cells produced from $CD14^+$ monocyte were cultured for five days with GM-CSF and IL-4, and then cultured for one day with Echinacea in experiment 3, but were done without Echinacea in experiment 4. Results : In experiments 1 and 2, there were 17 significantly expressed genes with average expression ratios above 2.5, including interferon gamma-inducible protein 30(IFI 30), CDC(cell-division-cylcle)-like kinase 2(CLK 2), syndecan binding protein(syntenin), superoxide dismutase 2, etc. In experiments 3 and 4, there were 24 gene, with significantly expressed genes were 24 genes, which were insulin-like growth factor 2(somatomedin A), methyl-CpG binding domain protein 3, IFI 30, small inducible cytokine subfamily A, member 22, etc. The genes encoding CD44, IFI 30, mannose receptor C type 1(MRC 1), chemokine receptor 7(CCR 7), CLK 2, syntenin and cytochrome C oxidase subunit VIII were significantly expressed in both monocytes and dendritic cells cultured with Echinacea. Conclusion : This study employed a cDNA microarray chip to elicit the immune-associated gene profile; the expression was enhanced by Echinacea in CD14+ monocytes and dendritic cells. Thus we laid the basis for the quantitative and functional analysis of genes induced by Echinacea in monocytes and monocyte-derived dendritic cells.