• Title/Summary/Keyword: signal pathways

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In silico analysis of candidate genes involved in light sensing and signal transduction pathways in soybean

  • Quecini, V.;Zucchi, M.I.;Pinheiro, J.B.;Vello, N.A.
    • Plant Biotechnology Reports
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    • v.2 no.1
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    • pp.59-73
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    • 2008
  • Several aspects of photoperception and light signal transduction have been elucidated by studies with model plants. However, the information available for economically important crops, such as Fabaceae species, is scarce. In order to incorporate the existing genomic tools into a strategy to advance soybean research, we have investigated publicly available expressed sequence tag (EST) sequence databases in order to identify Glycine max sequences related to genes involved in light-regulated developmental control in model plants. Approximately 38,000 sequences from open-access databases were investigated, and all bona fide and putative photoreceptor gene families were found in soybean sequence databases. We have identified G. max orthologs for several families of transcriptional regulators and cytoplasmic proteins mediating photoreceptor-induced responses, although some important Arabidopsis phytochrome-signaling components are absent. Moreover, soybean and Arabidopsis genefamily homologs appear to have undergone a distinct expansion process in some cases. We propose a working model of light perception, signal transduction and response-eliciting in G. max, based on the identified key components from Arabidopsis. These results demonstrate the power of comparative genomics between model systems and crop species to elucidate several aspects of plant physiology and metabolism.

A systematic mRNA control mechanism for germline stem cell homeostasis and cell fate specification

  • Lee, Myon-Hee;Mamillapalli, Srivalli Swathi;Keiper, Brett D.;Cha, Dong Seok
    • BMB Reports
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    • v.49 no.2
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    • pp.93-98
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    • 2016
  • Germline stem cells (GSCs) are the best understood adult stem cell types in the nematode Caenorhabditis elegans, and have provided an important model system for studying stem cells and their cell fate in vivo, in mammals. In this review, we propose a mechanism that controls GSCs and their cell fate through selective activation, repression and mobilization of the specific mRNAs. This mechanism is acutely controlled by known signal transduction pathways (e.g., Notch signaling and Ras-ERK MAPK signaling pathways) and P granule (analogous to mammalian germ granule)-associated mRNA regulators (FBF-1, FBF-2, GLD-1, GLD-2, GLD-3, RNP-8 and IFE-1). Importantly, all regulators are highly conserved in many multi-cellular animals. Therefore, GSCs from a simple animal may provide broad insight into vertebrate stem cells (e.g., hematopoietic stem cells) and their cell fate specification.

Therapeutic potential of targeting kinase inhibition in patients with idiopathic pulmonary fibrosis

  • Kim, Suji;Lim, Jae Hyang;Woo, Chang-Hoon
    • Journal of Yeungnam Medical Science
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    • v.37 no.4
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    • pp.269-276
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    • 2020
  • Fibrosis is characterized by excessive accumulation of extracellular matrix components. The fibrotic process ultimately leads to organ dysfunction and failure in chronic inflammatory and metabolic diseases such as pulmonary fibrosis, advanced kidney disease, and liver cirrhosis. Idiopathic pulmonary fibrosis (IPF) is a common form of progressive and chronic interstitial lung disease of unknown etiology. Pathophysiologically, the parenchyma of the lung alveoli, interstitium, and capillary endothelium becomes scarred and stiff, which makes breathing difficult because the lungs have to work harder to transfer oxygen and carbon dioxide between the alveolar space and bloodstream. The transforming growth factor beta (TGF-β) signaling pathway plays an important role in the pathogenesis of pulmonary fibrosis and scarring of the lung tissue. Recent clinical trials focused on the development of pharmacological agents that either directly or indirectly target kinases for the treatment of IPF. Therefore, to develop therapeutic targets for pulmonary fibrosis, it is essential to understand the key factors involved in the pathogenesis of pulmonary fibrosis and the underlying signaling pathway. The objective of this review is to discuss the role of kinase signaling cascades in the regulation of either TGF-β-dependent or other signaling pathways, including Rho-associated coiled-coil kinase, c-jun N-terminal kinase, extracellular signal-regulated kinase 5, and p90 ribosomal S6 kinase pathways, and potential therapeutic targets in IPF.

Activation of CREB by PKA Promotes the Chondrogeneic Differentiation of Chick Limb Bud Mesenchymal Cells

  • Kim, Kook-Hee;Lee, Young-Sup
    • Animal cells and systems
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    • v.13 no.3
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    • pp.289-295
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    • 2009
  • Cyclic AMP-mediated signaling pathways regulate a number of cellular functions. In this study, we examined the regulatory role of cAMP signaling pathways in chondrogenesis of chick limb bud mesenchymal cells in vitro. Forskolin, which increases cellular cAMP levels by the activation of adenylate cyclase, enhanced chondrogenic differentiation. Inhibition of PKA with specific inhibitors (H89 or KT5720) blocked pre-cartilage condensation stage, indicating that chondrogenesis is regulated by the increase in cellular cAMP level and subsequent activation of PKA. Downstream signaling pathway of PKA leading to gene expression was investigated by examination of several nuclear transcription factors. Forskolin treatment increased transcription level for a cartilage-specific marker gene Sox9. However, inhibition of PKA with H89 led to restore expression of Sox9, indicating PKA activity was required to regulate the expression of Sox9 in chondrogenesis. In addition, CREB was highly phosphorylated at early stage of mesenchyme culture, and followed by progressive dephosphorylation. CBP and ATF, another CRE related proteins were transiently expressed at the early stage of chondrogenesis with a pattern similar to CREB phosphorylation. Electrophoretic mobility shift assays confirmed that the binding activity of CREB to the CRE is closely correlated to the phosphorylation pattern of CREB. Therefore, cAMP-mediated signal transduction to nuclear events for the induction of genes appeared to be required at the early stage of chick limb bud chondrogenesis.

BIOLOGY ORIENTED TARGET SPECIFIC LITERATURE MINING FOR GPCR PATHWAY EXTRACTION (GPCR 경로 추출을 위한 생물학 기반의 목적지향 텍스트 마이닝 시스템)

  • KIm, Eun-Ju;Jung, Seol-Kyoung;Yi, Eun-Ji;Lee, Gary-Geunbae;Park, Soo-Jun
    • Proceedings of the Korean Society for Bioinformatics Conference
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    • 2003.10a
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    • pp.86-94
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    • 2003
  • Electronically available biological literature has been accumulated exponentially in the course of time. So, researches on automatically acquiring knowledge from these tremendous data by text mining technology become more and more prosperous. However, most of the previous researches are technology oriented and are not well focused in practical extraction target, hence result in low performance and inconvenience for the bio-researchers to actually use. In this paper, we propose a more biology oriented target domain specific text mining system, that is, POSTECH bio-text mining system (POSBIOTM), for signal transduction pathway extraction, especially for G protein-coupled receptor (GPCR) pathway. To reflect more domain knowledge, we specify the concrete target for pathway extraction and define the minimal pathway domain ontology. Under this conceptual model, POSBIOTM extracts interactions and entities of pathways from the full biological articles using a machine learning oriented extraction method and visualizes the pathways using JDesigner module provided in the system biology workbench (SBW) [14]

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Proliferative and Synthetic Responses of Airway Smooth Muscle in Asthma (천식에서 기도평활근의 증식과 합성 반응에 대한 최신지견)

  • Shim, Jung Yeon
    • Clinical and Experimental Pediatrics
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    • v.48 no.6
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    • pp.580-587
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    • 2005
  • New evidence is emerging that airway smooth muscle(ASM) may act as an immunomodulatory cell by providing pro-inflammatory cytokines and chemokines, polypeptide growth factors, extracellular matrix proteins, cell adhesion receptors and co-stimulatory molecules. ASM can promote the formation of the interstitial extracellular matrix, and potentially contribute to the alterations within the extracellular matrix in asthma. In addition, extracellular matrix components can alter the proliferative, survival, and cytoskeletal synthetic function of ASM cells through integrin-directed signaling. Increased ASM mass is one of the most important features of the airway wall remodeling process in asthma. Three different mechanisms may contribute to the increased ASM mass : cell proliferation, increased migration and decreased rate of apoptosis. The major signaling pathways of cell proliferation activated by ASM mitogens are those dependent on extracellular signal-regulated kinase and phosphoinositide 3'-kinase. The key signaling mechanisms of cell migration have been identified as the p38 mitogen-activated protein kinase and the p21-activated kinase 1 pathways. ASM cells contain ${\beta}2$-adrenergic receptors and glucocorticoid receptors. They may represent a key target for ${\beta}2$-adrenergic receptor agonist/corticosteroid interactions which have antiproliferative activity against a broad spectrum of mitogens.

The pepsinolytic hydrolysate from Johnius belengerii frame inhibited LPS-stimulated production of pro-inflammatory mediators via the inactivating of JNK and NF-κB pathways in RAW 264.7 macrophages

  • Heo, Seong-Yeong;Ko, Seok-Chun;Jung, Won-Kyo
    • Fisheries and Aquatic Sciences
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    • v.21 no.5
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    • pp.14.1-14.8
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    • 2018
  • The objective of this study was to investigate the anti-inflammatory effects of the pepsinolytic hydrolysate from the fish frame, Johnius belengerii, on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The J. belengerii frame hydrolysate (JFH) significantly suppressed nitric oxide (NO) secretion on LPS-stimulated RAW264.7 macrophages. Moreover, the JFH markedly inhibited the levels of protein and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, the LPS-stimulated mRNA expression of pro-inflammatory cytokines, including tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 was downregulated when cells were cultured with the JFH. The JFH significantly reduced the phosphorylation of c-Jun N-terminal kinase (JNK) and the translocation of nuclear factor-kappa B ($NF-{\kappa}B$) in macrophages. As the result, the JFH has the potential anti-inflammatory activity via blocking the JNK and $NF-{\kappa}B$ signal pathways.

Src Protein Tyrosine Kinases in Stress Responses

  • Grishin, Anatoly;Corey, Seth J.
    • Animal cells and systems
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    • v.6 no.1
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    • pp.1-12
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    • 2002
  • A role of Src family protein Tyrosine kinases (SFK) as mediators of receptor-ligand initiated responses is well established. Well documented, but less well understood is the role of SFK in cellular reaction to stresses. Evidence from the wide variety of experimental systems indicates that SFK mediate responses to all major classes of stress, including oxidation, DNA damage, mechanical impacts, and protein denaturing. SFK may be activated by stresses directly or via regulatory circuits whose identity is not yet fully understood. Depending on the cell type and the nature of activating stimulus, SFK may activate known downstream signaling cascades leading to cell survival, proliferation, cytoskeletal rearrangement, and apoptosis; the identity of these cascades is discussed. As in the case of receptor-initiated signaling, roles of individual SFK in various stress response may be redundant or non-redundant. Although signals generated by different stresses are generally transduced via distinct SFK pathways, these pathways may overlap or exhibit crosstalk. In some cell types stress-induced activation of SFK promotes survival and inhibits apoptosis, whereas the opposite may be true for other cell types. Stress responses constitute a new and rapidly developing area of SFK-mediated signaling.

Suppression of the TRIF-Dependent Signaling Pathway of Toll-Like Receptors by Isoliquiritigenin in RAW264.7 Macrophages

  • Park, Se-Jeong;Song, Ho-Yeon;Youn, Hyung-Sun
    • Molecules and Cells
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    • v.28 no.4
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    • pp.365-368
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    • 2009
  • Toll-like receptors (TLRs) play an important role in host defense by sensing invading microbial pathogens and initiating innate immune responses. The stimulation of TLRs by microbial components triggers the activation of myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-${\beta}$ (TRIF)-dependent downstream signaling pathways. Isoliquiritigenin (ILG), an active ingredient of Licorice, has been used for centuries to treat many chronic diseases. ILG inhibits the MyD88-dependent pathway by inhibiting the activity of inhibitor-${\kappa}B$ kinase. However, it is not known whether ILG inhibits the TRIF-dependent pathway. To evaluate the therapeutic potential of ILG, we examined its effect on signal transduction via the TRIF-dependent pathway of TLRs induced by several agonists. ILG inhibited nuclear factor-${\kappa}B$ and interferon regulatory factor 3 activation induced by lipopolysaccharide or polyinosinic-polycytidylic acid. ILG inhibited the lipopolysaccharide-induced phosphorylation of interferon regulatory factor 3 as well as interferon-inducible genes such as interferon inducible protein-10, and regulated activation of normal T-cell expressed and secreted (RANTES). These results suggest that ILG can modulate TRIF-dependent signaling pathways of TLRs, leading to decreased inflammatory gene expression.

Molecular Genetics of Emericella nidulans Sexual Development

  • Han, Kap-Hoon
    • Mycobiology
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    • v.37 no.3
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    • pp.171-182
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    • 2009
  • Many aspergilli that belongs to ascomycetes have sexuality. In a homothallic or self-fertile fungus, a number of fruiting bodies or cleistothecia are formed in a thallus grown from a single haploid conidia or ascospores. Genome-sequencing project revealed that two mating genes (MAT) encoding the regulatory proteins that are necessary for controlling partner recognition in heterothallic fungi were conserved in most aspergilli. The MAT gene products in some self-fertile species were not required for recognition of mating partner at pheromone-signaling stage but required at later stages of sexual development. Various environmental factors such as nutritional status, culture conditions and several stresses, influence the decision or progression of sexual reproduction. A large number of genes are expected to be involved in sexual development of Emericella nidulans (anamorph: Aspergillus nidulans), a genetic and biological model organism in aspergilli. The sexual development process can be grouped into several development stages, including the decision of sexual reproductive cycle, mating process, growth of fruiting body, karyogamy followed by meiosis, and sporulation process. Complicated regulatory networks, such as signal transduction pathways and gene expression controls, may work in each stage and stage-to-stage linkages. In this review, the components joining in the regulatory pathways of sexual development, although they constitute only a small part of the whole regulatory networks, are briefly mentioned. Some of them control sexual development positively and some do negatively. Regarding the difficulties for studying sexual differentiation compare to asexual one, recent progresses in molecular genetics of E. nidulans enlarge the boundaries of understanding sexual development in the non-fertile species as well as in fertile fungi.