• 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.

• Molecules and Cells
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• v.42 no.9
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• pp.646-660
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• 2019

Abscisic acid (ABA) is a phytohormone essential for seed development and seedling growth under unfavorable environmental conditions. The signaling pathway leading to ABA response has been established, but relatively little is known about the functional regulation of the constituent signaling components. Here, we present several lines of evidence that Arabidopsis Raf-like kinase Raf10 modulates the core ABA signaling downstream of signal perception step. In particular, Raf10 phosphorylates subclass III SnRK2s (SnRK2.2, SnRK2.3, and SnRK2.6), which are key positive regulators, and our study focused on SnRK2.3 indicates that Raf10 enhances its kinase activity and may facilitate its release from negative regulators. Raf10 also phosphorylates transcription factors (ABI5, ABF2, and ABI3) critical for ABA-regulted gene expression. Furthermore, Raf10 was found to be essential for the in vivo functions of SnRK2s and ABI5. Collectively, our data demonstrate that Raf10 is a novel regulatory component of core ABA signaling.

• Journal of the korean academy of Pediatric Dentistry
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• v.26 no.4
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• pp.652-663
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• 1999

Craniosynostosis, the premature fusion of cranial sutures, presumably involves disturbance of the interactions between different tissues within the cranial sutures. Interestingly, point mutaions in the genes encoding for the fibroblast growth factor receptors(FGFRs), especially FGFR2, cause various types of human craniosynostosis syndromes. To elucidate the function of these genes in the early morphogenesis of mouse cranial sutures, we first analyzed by in situ hybridization the expression of FGFR2(BEK) and osteopontin, an early marker of osteogenic differentiation, in the sagittal suture of calvaria during embryonic(E15-E18) and postnatal stage(P1-P3). FGFR2(BEK) was intensely expressed in the osteogenic fronts, whose cells undergo differentiation into osteoprogenitor cells that ultimately lay down the bone matrix. Osteopontin was expressed throughout the parietal bones excluding the osteogenic fronts, the periphery of the parietal bones. To further examine the role of FGF-mediated FGFR signaling in cranial suture, we did in vitro experiments in E15.5 mouse calvarial explants. Interestingly, implantation of FGF2 soaked beads onto both the osteogenic fronts and mid-mesenchyme of sagittal suture after 36 hours organ culture resulted in the increase of the tissue thickness and cell number around FGF2 beads, moreover FGF4-soaked beads implanted onto the osteogenic fronts stimulated suture closure due to an accelerated bone growth, compared to FGF4 beads placed onto mid-mesenchyme of sagittal suture and BSA control beads. In addition FGF2 induced the ectopic expression of osteopontin and Msx1 genes. Taken together, these data indicate that FGF-mediated FGFR signaling has a important role in regulating the cranial bone growth and maintenance of cranial suture, and suggest that FGF-mediated FGFR signaling is involved in regulating the balance between the cell proliferation and differentiation through inducing the expression of osteopontin and Msx1 genes.

• Journal of Microbiology and Biotechnology
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• v.21 no.7
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• pp.686-696
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• 2011

To deal with pathogens, plants have evolved sophisticated mechanisms including constitutive and induced defense mechanisms. Phytohormones play important roles in plant growth and development, as well as in the systemic response induced by beneficial and pathogen microorganisms. In this work, we identified an Aspergillus ustus isolate that promotes growth and induces developmental changes in Solanum tuberosum and Arabidopsis thaliana. A. ustus inoculation on A. thaliana and S. tuberosum roots induced an increase in shoot and root growth, and lateral root and root hair numbers. Assays performed on Arabidopsis lines to measure reporter gene expression of auxin-induced/ repressed or cell cycle controlled genes (DR5 and CycB1, respectively) showed enhanced GUS activity, when compared with mock-inoculated seedlings. To determine the contribution of phytohormone signaling pathways in the effect elicited by A. ustus, we evaluated the response of a collection of hormone mutants of Arabidopsis defective in auxin, ethylene, cytokinin, or abscisic acid signaling to the inoculation with this fungus. All mutant lines inoculated with A. ustus showed increased biomass production, suggesting that these genes are not required to respond to this fungus. Moreover, we demonstrated that A. ustus synthesizes auxins and gibberellins in liquid cultures. In addition, A. ustus induced systemic resistance against the necrotrophic fungus Botrytis cinerea and the hemibiotrophic bacterium Pseudomonas syringae DC3000, probably through the induction of the expression of salicylic acid, jasmonic acid/ethylene, and camalexin defense-related genes in Arabidopsis.

• Archives of Plastic Surgery
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• v.42 no.1
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• pp.11-19
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• 2015

Background Wound healing is an interaction of a complex signaling cascade of cellular events, including inflammation, proliferation, and maturation. $K^+$ channels modulate the mitogen-activated protein kinase (MAPK) signaling pathway. Here, we investigated whether $K^+$ channel-activated MAPK signaling directs collagen synthesis and angiogenesis in wound healing. Methods The human skin fibroblast HS27 cell line was used to examine cell viability and collagen synthesis after potassium chloride (KCl) treatment by Cell Counting Kit-8 (CCK-8) and western blotting. To investigate whether $K^+$ ion channels function upstream of MAPK signaling, thus affecting collagen synthesis and angiogenesis, we examined alteration of MAPK expression after treatment with KCl (channel inhibitor), NS1619 (channel activator), or kinase inhibitors. To research the effect of KCl on angiogenesis, angiogenesis-related proteins such as thrombospondin 1 (TSP1), anti-angiogenic factor, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), pro-angiogenic factor were assayed by western blot. Results The viability of HS27 cells was not affected by 25 mM KCl. Collagen synthesis increased dependent on time and concentration of KCl exposure. The phosphorylations of MAPK proteins such as extracellular-signal-regulated kinase (ERK) and p38 increased about 2.5-3 fold in the KCl treatment cells and were inhibited by treatment of NS1619. TSP1 expression increased by 100%, bFGF expression decreased by 40%, and there is no significant differences in the VEGF level by KCl treatment, TSP1 was inhibited by NS1619 or kinase inhibitors. Conclusions Our results suggest that KCl may function as a therapeutic agent for wound healing in the skin through MAPK signaling mediated by the $K^+$ ion channel.

• Asia-Pacific Journal of Business Venturing and Entrepreneurship
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• v.13 no.3
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• pp.113-124
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• 2018

The objective of this study is to examine the effectiveness of signals and advancing our understanding of the relationship between ratings and audience decisions based on the signaling theory. Though many studies argue that information asymmetry affects decision making, few studies have examined two key signaling factors: its potential to have multiple sources and the effect of time on its effectiveness. This study examined how experts' and the general audience's ratings affect decision making. We also considered change patterns in ratings to explore how time effect on ratings affect selection behavior. We tested our hypotheses using the latent growth model based on signaling theory and behavior approaches. The results show that a general audience's ratings is perceived as more credible than are those of experts and that audience members are significantly affected by upward patterns in ratings. The findings suggest that general audiences play a critical role as signal providers. Thus, market participants such as producers should pay more attention to the general audience's ratings in order to increase revenues. They should also consider the time effect of signaling, such as upward trends in ratings.

• Journal of Plant Biotechnology
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• v.44 no.3
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• pp.264-270
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• 2017

Brassinosteroid (BR), a plant steroid hormone, plays a critical role in the growth and developmental processes through its canonical signaling and crosstalk with various internal and external signaling pathways. Recent studies have revealed the essential interplay mechanisms between BR and ABA during seed germination and early seedling establishment. However, molecular mechanisms for this important signaling crosstalk are largely unknown. To understand the crosstalk between BR-mediated signaling pathways and ABA functions during early seedling development, we carried out a comparative genome-wide transcriptome analysis with an Agilent Arabidopsis $4{\times}44K$ oligo chip. We selected and compared the expression patterns of ABA response genes in ABA-insensitive bes1-D mutant with wild type seedlings on which ABA was exogenously applied. As a result, we identified 2,353 significant differentially expressed genes (DEGs) in ABA-treated bes1-D and wild type seedlings. GO enrichment analysis revealed that ABA signaling, response, and metabolism were critically down-regulated by BR-activated signaling pathways. In addition, the genome-wide transcriptome analysis data revealed that BR-regulated signaling pathways were tightly connected to diverse signal cues including abiotic/biotic stress, auxin, ROS etc. In this study, we newly identified the molecular mechanisms of BR-mediated repression of ABA signaling outputs. Also, our data suggest that interplay among diverse signaling pathways is critical for the adaptive response of the plant to various environmental factors.

• Research in Plant Disease
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• v.20 no.1
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• pp.1-7
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• 2014

Plant growth is considered the sum of cell proliferation and subsequent elongation of the cells. The continuous proliferation and elongation of plant cells are vital to the production of new organs, which have a significant impact on overall plant growth. Accordingly, the relationship between environmental stimuli, such as temperature, light, wind, and sound waves to plant growth is of great interest in studies of plant development. Sound waves can have negative or positive effects on plant growth. In this review paper we have summarized the relationship between sound waves and plant growth response. Sound waves with specific frequencies and intensities can have positive effects on various plant biological indices including seed germination, root elongation, plant height, callus growth, cell cycling, signaling transduction systems, enzymatic and hormonal activities, and gene expression.

• BMB Reports
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• v.38 no.1
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• pp.1-8
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• 2005

Transforming growth factor-$\beta$ is a pleiotropic growth factor that has enthralled many investigators for approximately two decades. In addition to many reports that have clarified the basic mechanism of transforming growth factor-$\beta$ signal transduction, numerous laboratories have published on the clinical implication/application of transforming growth factor-$\beta$. To name a few, dysregulation of transforming growth factor-$\beta$ signaling plays a role in carcinogenesis, autoimmunity, angiogenesis, and wound healing. In this report, we will review these clinical implications of transforming growth factor-$\beta$.

• Journal of the korean academy of Pediatric Dentistry
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• v.30 no.2
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• pp.217-228
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• 2003

Co-ordinate growth of the brain and skull is achieved through a series of tissue interactions between the developing brain, the growing bones of the skull and the sutures that unite the bones. Craniosynostosis, the premature fusion of cranial sutures, presumably involves disturbance of these interactions. Bmp2, one of bone morphogenetic proteins (Bmps), is involved in the regulation of the shapes of individual bones and the relative proportions of the skeleton. Mutations in the homeobox gene Msx2, known as a downstream gene of Bmp, cause Boston-type human craniosynostosis. The phenotype of Dlx5 homozygote mutant mouse presents craniofacial abnormalities including a delayed ossification of calvarial bone. These facts suggest important roles of Bmp2, Msx2 and Dlx5 genes in the cranial bone growth and suture morphogenesis. To elucidate the function of these molecules in the early morphogenesis of mouse cranial sutures, we first analyzed by in situ hybridization the expression of Bmp2(E15-18), Msx2 and Dlx5 genes in the developing sagittal suture of calvaria during the embryonic stage. Bmp2 mRNA was intensely expressed in the osteogenic fronts and also at the low level in the periosteum of parietal bones during embryonic stage, Msx2 mRNA was intensely expressed in the sutural mesenchyme and mildly expressed in the dura mater during the embryonic stage. Dlx5 mRNA was intensely expressed osteogenic fronts and parietal bones. To further examine the role of Bmp signaling in cranial suture, we did in vitro experiments in E15.5 mouse calvarial explants. Interestingly, implantation of Bmp2-soaked beads onto the osteogenic fronts after 48 hours organ culture resulted in the increase of the tissue thickness and cell number around Bmp2 beads, compared to BSA control beads. In addition Bmp2 induced etopic expressions of Msx2 and Dlx5 genes. On the other hand, overexpression of FGF2 did not induce the expression of Msx2 and Dlx5. Taken together, these data indicate that Bmp2 signaling molecule has a important role in regulating the cranial bone growth and early morphogenesis of cranial suture. We also suggest that Bmp signaling is involved in all the stages of osteogenesis of cranial bones and the maintenance of cranial suture by regulating Msx2 and Dlx5 genes, and that Msx2 and Dlx5 genes are specific transcription factors of Bmp signaling pathway.