• IMMUNE NETWORK
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• v.9 no.3
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• pp.75-83
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• 2009

Recent years have seen an explosion of new knowledge defining the molecular events that are critical for development and activation of immune cells. Much of this new information has come from a careful molecular dissection of key signal transduction pathways that are initiated when immune cell receptors are engaged. In addition to the receptors themselves and critical effector molecules, these signaling pathways depend on adapters, proteins that have no intrinsic effector function but serve instead as scaffolds to nucleate multimolecular complexes. This review summarizes some of what has been learned about one such adapter protein, SH2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76), and how it regulates and integrates signals after engagement of immunoreceptors and integrins on various immune cell lineages.

• Biomolecules & Therapeutics
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• v.30 no.1
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• pp.72-79
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• 2022

Licochalcone H (LCH) is a phenolic compound synthetically derived from licochalcone C (LCC) that exerts anticancer activity. In this study, we investigated the anticancer activity of LCH in human skin cancer A375 and A431 cells. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) cell viability assay was used to evaluate the antiproliferative activity of LCH. Cell cycle distribution and the induction of apoptosis were analyzed by flow cytometry. Western blotting assays were performed to detect the levels of proteins involved in cell cycle progression, apoptosis, and the JAK2/STAT3 signaling pathway. LCH inhibited the growth of cells in dose- and time-dependent manners. The annexin V/propidium iodide double staining assay revealed that LCH induced apoptosis, and the LCH-induced apoptosis was accompanied by cell cycle arrest in the G1 phase. Western blot analysis showed that the phosphorylation of JAK2 and STAT3 was decreased by treatment with LCH. The inhibition of the JAK2/STAT3 signaling pathway by pharmacological inhibitors against JAK2/STAT3 (cryptotanshinone (CTS) and S3I-201) simulated the antiproliferative effect of LCH suggesting that LCH induced apoptosis by modulating JAK2/STAT3 signaling.

• Herbal Formula Science
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• v.25 no.3
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• pp.349-362
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• 2017

Objectives : We investigated whether the components of Ailanthus altissima induced apoptotic cell death in Jurkat acute lymphoblastic leukemia (ALL) cells. Methods : Regulation of cell proliferation is a complex process involving the regulated expression and/or modification of discrete gene products, which control transition between different stages of the cell cycle. Results : Upon treatments with Ailanthus altissima, the concentration-dependent inhibitions of cell viability were observed as compared to untreated control group. The capability of Ailanthus altissima to induce apoptosis was associated with proteolytic cleavage of specific target proteins such as poly(ADP-ribose)polymerase (PARP) and beta-catenin proteins suggesting the possible involvement of caspases. Ailanthus altissima also caused apoptosis as measured by cell morphology and DNA fragmentation. Conclusions : These results indicate that the increase of apoptotic cell death by Ailanthus altissima may be due to the inhibition of cell cycle in human Jurkat lymphocytes. Conclusively, these current and further findings will provide novel approaches to understanding and treating major diseases.

• 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.

• Molecules and Cells
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• v.41 no.2
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• pp.103-109
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• 2018

Calcium ions are involved in the regulation of diverse cellular processes. Fourteen genes encoding calcium binding proteins have been identified in Dictyostelium. CBP7, one of the 14 CBPs, is composed of 169 amino acids and contains four EF-hand motifs. Here, we investigated the roles of CBP7 in the development and cell migration of Dictyostelium cells and found that high levels of CBP7 exerted a negative effect on cells aggregation during development, possibly by inhibiting chemoattractant-directed cell migration. While cells lacking CBP7 exhibited normal development and chemotaxis similar that of wild-type cells, CBP7 overexpressing cells completely lost their chemotactic abilities to move toward increasing cAMP concentrations. This resulted in inhibition of cellular aggregation, a process required for forming multicellular organisms during development. Low levels of cytosolic free calcium were observed in CBP7 overexpressing cells, which was likely the underlying cause of their lack of chemotaxis. Our results demonstrate that CBP7 plays an important role in cell spreading and cell-substrate adhesion. cbp7 null cells showed decreased cell size and cell-substrate adhesion. The present study contributes to further understanding the role of calcium signaling in regulation of cell migration and development.

• Parasites, Hosts and Diseases
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• v.59 no.5
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• pp.501-505
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• 2021

The pathogenic free-living amoeba Naegleria fowleri causes primary amoebic meningoencephalitis, a fatal infection, by penetrating the nasal mucosa and migrating to the brain via the olfactory nerves. N. fowleri can induce host cell death via lytic necrosis. Similar to phosphorylation, O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) is involved in various cell-signaling processes, including apoptosis and proliferation, with O-GlcNAc addition and removal regulated by O-GlcNAc transferase and O-GlcNAcase (OGA), respectively. However, the detailed mechanism of host cell death induced by N. fowleri is unknown. In this study, we investigated whether N. fowleri can induce the modulation of O-GlcNAcylated proteins during cell death in Jurkat T cells. Co-incubation with live N. fowleri trophozoites increased DNA fragmentation. In addition, incubation with N. fowleri induced a dramatic reduction in O-GlcNAcylated protein levels in 30 min. Moreover, pretreatment of Jurkat T cells with the OGA inhibitor PUGNAc prevented N. fowleri-induced O-deGlcNAcylation and DNA fragmentation. These results suggest that O-deGlcNAcylation is an important signaling process that occurs during Jurkat T cell death induced by N. fowleri.

• Herbal Formula Science
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• v.31 no.1
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• pp.41-51
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• 2023

Objectives : Raphani Semen (Raphanus sativus L.) is known for the various beneficial effects in Korean medicine. This study aimed to investigate the effect of Raphani Semen extract (RSE) against arachidonic acid (AA)+iron-induced oxidative stress in cells. Methods : Ingredients, their target information, oxidative stress liver injury-related proteins was obtained from various network pharmacology databases and software. A hypergeometric test and enrichment analysis were conducted to evaluate associations between protein targets of RSE. The cell viability was assessed by MTT assay, and immunoblot analysis was used to confirm the molecular mechanisms. Results : A compound-target network of RSE was constructed, which consisted of 336 edges between 18 ingredients and 123 protein targets. PI3K-Akt signaling pathway, ErbB signaling pathway, HIF-1 signaling pathway, PPAR signaling pathway, and AMPK signaling pathway was significantly associated with protein targets of RSE. RSE protected HepG2 cells against AA+iron-induced oxidative stress as mediated with AMPK signaling. Conclusion : RSE was found to protect the cells against oxidative stress via the AMPK signaling pathway.

• International Journal of Oral Biology
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• v.34 no.2
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• pp.53-59
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• 2009

Periodontal ligament (PDL) tissue is a connective tissue that is interposed between the roots of the teeth and the inner wall of the alveolar bone socket. PDL is always exposed to physiologic mechanical force such as masticatory force and PDL cells play important roles during orthodontic tooth movement by synthesizing and secreting different mediators involved in bone remodeling. The Wnt/${\beta}$-catenin signaling pathway was recently shown to play a significant role in the control of bone formation. In the present study, we applied cyclic tensile stress of 20% elongation to cultured human PDL cells and assessed its impact after six days upon components of the Wnt/${\beta}$-catenin signaling pathway. RTPCR analysis showed that Wnt1a, Wnt3a, Wnt10b and the Wnt receptor LRP5 were down-regulated, whereas the Wnt inhibitor DKK1 was up-regulated in response to these stress conditions. In contrast, little change was detected in the mRNA expression of Wnt5a, Wnt7b, Fz1, and LRP6. By western blotting we found decreased expression of the ${\beta}$-catenin and p-GSK-3${\beta}$ proteins. Our results thus show that mechanical stress suppresses the canonical Wnt/${\beta}$-catenin signaling pathway in PDL cells.

• BMB Reports
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• v.34 no.5
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• pp.484-488
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• 2001

STATs are proteins with a dual function: signal transducers in the cytoplasm and transcriptional activators in the nucleus. Among the six known major STATs (STAT1-6), STAT3 has been implicated in the widest range of signaling pathways that regulate cell growth and differentiation. As a part of our on-going investigation on the pleiotropic functions of STAT proteins, we examined the role of STAT3 as a molecular adaptor that links diverse cell growth signaling pathways. We observed that STAT3 can be specifically activated by multiple cytokines, such as IL-3, in transformed fibroblasts and IL-4 or IFN-$\gamma$ in primary immune cells, respectively. The selective activation of STAT3 in H-ras-transformed NIH3T3 cells is associated with an increased expression of phosphoserioe STAT3 in these cells, compared to the parental cells. Notably phosphoresine-STAT3 interacts with oncogenic ras, shown by immunoprecipitation and Western blots. The results suggest the role of STAT3 in rasinduced cellular transformation as a molecular adaptor linking the Jak/STAT and Ras/MAPK pathways. In primary immune cells, IL-4 and IFN-$\gamma$ each induced (in addition to the characteristic STAT6 and STAT1 homodimers) the formation of STAT3-containing complexes that bind to GAS probes, which correspond to the $Fe{\varepsilon}$ Rll and $Fe{\gamma}$ RI promoter sequences, respectively. Since IL-4 and IFN-$\gamma$ are known to counter-regulate the expression of these genes, the ability of STAT3 to form heterodimeric complexes with STAT6 or STAT1 implies its role in the fine-tuned control of genes that are regulated by IL-4 and IFN-$\gamma$.

• BMB Reports
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• v.51 no.10
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• pp.486-492
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• 2018

The CCN protein family is composed of six matricellular proteins, which serve regulatory roles rather than structural roles in the extracellular matrix. First identified as secreted proteins which are induced by oncogenes, the acronym CCN came from the names of the first three members: CYR61, CTGF, and NOV. All six members of the CCN family consist of four cysteine-rich modular domains. CCN proteins are known to regulate cell adhesion, proliferation, differentiation, and apoptosis. In addition, CCN proteins are associated with cardiovascular and skeletal development, injury repair, inflammation, and cancer. They function either through binding to integrin receptors or by regulating the expression and activity of growth factors and cytokines. Given their diverse roles related to the pathology of certain diseases such as fibrosis, arthritis, atherosclerosis, diabetic nephropathy, retinopathy, and cancer, there are many emerging studies targeting CCN protein signaling pathways in attempts to elucidate their potentials as therapeutic targets.