• Journal of Microbiology and Biotechnology
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• v.25 no.5
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• pp.637-647
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• 2015

In this study, we attempted to understand signaling pathways behind lipid biosynthesis by employing a chemical genetics approach based on small molecule inhibitors. Specific signaling inhibitors of MAP kinase or modulators of cAMP signaling were selected to evaluate the functional roles of each of the key signaling pathways in three different microalgal species: Chlamydomonas reinhardtii, Chlorella vulgaris, and Haematococcus pluvialis. Our results clearly indicate that cAMP signaling pathways are indeed positively associated with microalgal lipid biosynthesis. In contrast, MAP kinase pathways in three microalgal species are all negatively implicated in both lipid and carotenoid biosynthesis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7245-7249
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• 2014

Glucose regulated protein 78 (GRP78) is usually recognized as a chaperone in the endoplasmic reticulum. However, increasing evidence indicates that GRP78 can be translocated to the cell surface, acting as a signaling receptor for a variety of ligands. Since little is known about the secretion of GRP78 and its role in the progression of colon cancer we here focused on GRP78 from colon cancer cells, and purified GRP78 protein mimicking the secreted GRP78 was able to utilize cell surface GRP78 as its receptor, activating downstream PI3K/Akt and Wnt/${\beta}$-catenin signaling and promote colon cancer cell proliferation. Our study revealed a new mode of action of autocrine GRP78 in cancer progression: secreted GRP78 binds to cell surface GRP78 as its receptor and activates intracellular proliferation signaling.

• Bulletin of the Korean Chemical Society
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• v.34 no.4
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• pp.1269-1271
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• 2013

• Bulletin of the Korean Chemical Society
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• v.32 no.11
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• pp.4083-4085
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• 2011

• Korean Journal of Environmental Biology
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• v.22 no.4
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• pp.479-486
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• 2004

Phytoestrogens display estrogen-like activity because of their structural similarity to human estrogens and exhibit high affinity binding for the estrogen receptors (ERs). The prevalence of phytoestrogens in our diets and the biological effects that they may cause need to be fully examined. ER is the ancestral receptor from which all other steroid receptors have evolved. Although phytoestrogens serve specific signaling functions between the plants and insects, fungi, and bacteria, many chemical signals are often misinterpreted as estrogenic signals in non-target organisms such as vertebrates. There are no ERs in plants or in their most common partners, insects. However, Rhizobium soil bacteria have NodD proteins which is an intended target of phytoestrogen signaling and share genetic homology with the ER. These two evolutionarily distant receptors both recognize and respond to a shared group of chemical signals and ligands, including both agonists and antagonists. This review briefly summarizes estrogen and estrogen receptors, kinds of important phytoestrogens, their health effects as well as some of the evolutionary aspects of mechanism by which phytoestrogen mimics the endogenous ER signaling in our body.

• Bulletin of the Korean Chemical Society
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• v.29 no.3
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• pp.571-574
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• 2008

The well-known Cu2+-selective chemodosimetric behavior of rhodamine B hydrazide was successfully switched to selectivity for Hg2+. The fluorescence signaling is remarkably selective toward Hg2+ ions compared to other common biologically and environmentally important metal ions, including Cu2+ ions. The detection limit was 0.2 mM in an acetate-buffered aqueous 10% methanol solution at pH 5. The OFF-ON type of signaling is due to the selective Hg2+-induced hydrolysis of the lactam ring of the hydrazide as has been reported for the standard Cu2+-signaling process of the same compound. A simple change in medium resulted in clear switching of selective signaling from Cu2+ to Hg2+, which extends the applicability of the easily accessible hydrazide derivative.

• Bulletin of the Korean Chemical Society
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• v.31 no.12
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• pp.3539-3542
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• 2010

Selective mercuration at the 1,6-positions of 2-hydroxy derivative of Nile Red and its application towards $Hg^{2+}$-selective signaling was investigated. The 2-hydroxy Nile Red exhibited a selective UV-vis absorption and fluorescent signaling behavior towards $Hg^{2+}$ ions over common coexisting physiologically important metal ions in aqueous environment. $^1H$ NMR studies revealed that the mercuration was selectively effected at the 1,6-positions of 2-hydroxy Nile Red, which is quite different from that at the 6,8-positions for the parent Nile Red.

• Bulletin of the Korean Chemical Society
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• v.31 no.1
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• pp.246-249
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• 2010

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.2
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• pp.109-120
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• 2014

The epothilones are a class of microtubule inhibitors that exhibit a strong antitumor activity. UTD2 is a novel epothilone analog generated by genetic manipulation of the polyketide biosynthetic gene cluster. This study investigated the effects of UTD2 on the actin cytoskeleton and its critical regulators, and the signaling pathways which are essential for cell motility, growth and survival in MCF-7 breast cancer cells. Results showed that UTD2 inhibited the cellular functions of actin cytoskeleton, such as wound-closure, migration and invasion, as well as adhesion. Our study further demonstrated that UTD2 suppressed Rac1 GTPase activation and reduced the activity of PAK1, which is a downstream effector of Rac1, while the activity of Cdc42 was not affected. Additionally, the phosphorylation of p38 and ERK were significantly inhibited, but the phosphorylation of JNK remained the same after UTD2 treatment. Moreover, UTD2 inhibited the activity and mRNA expression of MMP-2, which plays a key role in cell motility. UTD2 also reduced the phosphorylation of Akt, which is an important signaling kinase regulating the cell survival through Rac1. Furthermore, UTD2 interrupted the synergy between Rac1 and Raf in focus formation assays. Taken together, these results indicated that UTD2 exerted multiple effects on the actin cytoskeleton and signaling pathways associated with Rac1. This study provided novel insights into the molecular mechanism of the antineoplastic and antimetastatic activities of epothilones. Our findings also suggest that the signaling pathways regulated by Rac1 may be evaluated as biomarkers for the response to therapy in clinical trials of epothilones.

• Journal of Ginseng Research
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• v.43 no.4
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• pp.527-538
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• 2019

Background: Ginsenoside Rg1 was shown to exert ligand-independent activation of estrogen receptor (ER) via mitogen-activated protein kinase-mediated pathway. Our study aimed to delineate the mechanisms by which Rg1 activates the rapid ER signaling pathways. Methods: ER-positive human breast cancer MCF-7 cells and ER-negative human embryonic kidney HEK293 cells were treated with Rg1 ($10^{-12}M$, $10^{-8}M$), $17{\beta}$-estradiol ($10^{-8}M$), or vehicle. Immunoprecipitation was conducted to investigate the interactions between signaling protein and ER in MCF-7 cells. To determine the roles of these signaling proteins in the actions of Rg1, small interfering RNA or their inhibitors were applied. Results: Rg1 rapidly induced $ER{\alpha}$ translocation to plasma membrane via caveolin-1 and the formation of signaling complex involving linker protein (Shc), insulin-like growth factor-I receptor, modulator of nongenomic activity of ER (MNAR), $ER{\alpha}$, and cellular nonreceptor tyrosine kinase (c-Src) in MCF-7 cells. The induction of extracellular signal-regulated protein kinase and mitogen-activated protein kinase kinase (MEK) phosphorylation in MCF-7 cells by Rg1 was suppressed by cotreatment with small interfering RNA against these signaling proteins. The stimulatory effects of Rg1 on MEK phosphorylation in these cells were suppressed by both PP2 (Src kinase inhibitor) and AG1478 [epidermal growth factor receptor (EGFR) inhibitor]. In addition, Rg1-induced estrogenic activities, EGFR and MEK phosphorylation in MCF-7 cells were abolished by cotreatment with G15 (G protein-coupled estrogen receptor-1 antagonist). The increase in intracellular cyclic AMP accumulation, but not Ca mobilization, in MCF-7 cells by Rg1 could be abolished by G15. Conclusion: Ginsenoside Rg1 exerted estrogenic actions by rapidly inducing the formation of ER containing signalosome in MCF-7 cells. Additionally, Rg1 could activate EGFR and c-Src ER-independently and exert estrogenic effects via rapid activation of membrane-associated ER and G protein-coupled estrogen receptor.