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Search Results: 1 - 10 of 7655 matches for " Jongsun Park "
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Contribution of Natural Inhibitors to the Understanding of the PI3K/PDK1/PKB Pathway in the Insulin-mediated Intracellular Signaling Cascade
Jae Youl Cho,Jongsun Park
International Journal of Molecular Sciences , 2008, DOI: 10.3390/ijms9112217
Abstract: The critical initial steps in insulin action include phosphorylation of adapter proteins and activation of phosphatidylinositol 3-kinase (PI3K). One of important components in this process is a protein called Akt/protein kinase B (PKB). The work of numerous different researchers indicates a role of PKB in regulating insulin-stimulated glucose uptake. The crucial role of lipid second messengers in PKB activation has been dissected through the use of the PI3K-specific inhibitors wortmannin and LY294002. Receptor-activated PI3K synthesizes the lipid second messenger PtdIns[3,4,5]-trisphosphate, leading to the recruitment of PKB to the membrane. Membrane attachment of PKB is mediated by its pleckstrin homology domain binding to PtdIns[3,4,5]-trisphosphate or PtdIns[3,4]-bisphosphate with high affinity. Activation of PKB alpha is then achieved at the plasma membrane by phosphorylation of Thr308 in the activation-loop of the kinase domain and Ser473 in the carboxy-terminal regulatory region, respectively. 3-Phosphoinositide-dependent protein kinase-1 (PDK1) is responsible for T308 phosphorylation. The usage of specific inhibitors and natural compound has significantly contributed to investigate the molecular mechanism of PI3K/PDK1/PKB signaling pathway, leading to the putative therapeutics benefits of patients. This review focuses on the contribution of natural inhibitor or compound in our understanding of the mechanism by which insulin induces, especially in PI3K/ PDK1/PKB signaling.
Whole transcriptome analyses of six thoroughbred horses before and after exercise using RNA-Seq
Park Kyung-Do,Park Jongsun,Ko Junsu,Kim Byung
BMC Genomics , 2012, DOI: 10.1186/1471-2164-13-473
Abstract: Background Thoroughbred horses are the most expensive domestic animals, and their running ability and knowledge about their muscle-related diseases are important in animal genetics. While the horse reference genome is available, there has been no large-scale functional annotation of the genome using expressed genes derived from transcriptomes. Results We present a large-scale analysis of whole transcriptome data. We sequenced the whole mRNA from the blood and muscle tissues of six thoroughbred horses before and after exercise. By comparing current genome annotations, we identified 32,361 unigene clusters spanning 51.83 Mb that contained 11,933 (36.87%) annotated genes. More than 60% (20,428) of the unigene clusters did not match any current equine gene model. We also identified 189,973 single nucleotide variations (SNVs) from the sequences aligned against the horse reference genome. Most SNVs (171,558 SNVs; 90.31%) were novel when compared with over 1.1 million equine SNPs from two SNP databases. Using differential expression analysis, we further identified a number of exercise-regulated genes: 62 up-regulated and 80 down-regulated genes in the blood, and 878 up-regulated and 285 down-regulated genes in the muscle. Six of 28 previously-known exercise-related genes were over-expressed in the muscle after exercise. Among the differentially expressed genes, there were 91 transcription factor-encoding genes, which included 56 functionally unknown transcription factor candidates that are probably associated with an early regulatory exercise mechanism. In addition, we found interesting RNA expression patterns where different alternative splicing forms of the same gene showed reversed expressions before and after exercising. Conclusion The first sequencing-based horse transcriptome data, extensive analyses results, deferentially expressed genes before and after exercise, and candidate genes that are related to the exercise are provided in this study.
Multiple implications of 3-phosphoinositide-dependent protein kinase 1 in human cancer
Yuwen Li,Keum-Jin Yang,Jongsun Park
World Journal of Biological Chemistry , 2010,
Abstract: 3-phosphoinositide-dependent protein kinase-1 (PDK1) is a central mediator of cellular signaling between phosphoinositide-3 kinase and various intracellular serine/threonine kinases, including protein kinase B, p70 ribosomal S6 kinase, serum and glucocorticoid-inducible kinase, and protein kinase C. PDK1 activates members of the AGC family of protein kinases by phosphorylating serine/threonine residues in the activation loop. Here, we review the regulatory mechanisms of PDK1 and its roles in cancer. PDK1 is activated by autophosphorylation in the activation loop and other serine residues, as well as by phosphorylation of Tyr-9 and Tyr-373/376. Src appears to recognize PDK1 following tyrosine phosphorylation. The role of heat shock protein 90 in regulating PDK1 stability and PDK1-Src complex formation are also discussed. Furthermore, we summarize the subcellular distribution of PDK1. Finally, an important role for PDK1 in cancer chemotherapy is proposed. In conclusion, a better understanding of its molecular regulatory mechanisms in various signaling pathways will help to explain how PDK1 acts as an oncogenic kinase in various cancers, and will contribute to the development of novel cancer chemotherapies.
Identification and analysis of in planta expressed genes of Magnaporthe oryzae
Soonok Kim, Jongsun Park, Sook-Young Park, Thomas K Mitchell, Yong-Hwan Lee
BMC Genomics , 2010, DOI: 10.1186/1471-2164-11-104
Abstract: A cDNA library was constructed with RNA from rice leaves (Oryza sativa cv. Hwacheong) infected with M. oryzae strain KJ201. To enrich for fungal genes, subtraction library using PCR-based suppression subtractive hybridization was constructed with RNA from infected rice leaves as a tester and that from uninfected rice leaves as the driver. A total of 4,148 clones from two libraries were sequenced to generate 2,302 non-redundant ESTs. Of these, 712 and 1,562 ESTs could be identified to encode fungal and rice genes, respectively. To predict gene function, Gene Ontology (GO) analysis was applied, with 31% and 32% of rice and fungal ESTs being assigned to GO terms, respectively. One hundred uniESTs were found to be specific to fungal infection EST. More than 80 full-length fungal cDNA sequences were used to validate ab initio annotated gene model of M. oryzae genome sequence.This study shows the power of ESTs to refine genome annotation and functional characterization. Results of this work have advanced our understanding of the molecular mechanisms underpinning fungal-plant interactions and formed the basis for new hypothesis.Rice blast, caused by Magnaporthe oryzae, is one of the most devastating diseases in rice growing regions worldwide, causing 11-15% yield loss annually [1]. Genetic tractability as well as economic importance makes this disease a model pathosystem to understand plant-microbe interactions. The genome sequences of both organisms are available [2-4], and both forward and reverse genomic studies to understand molecular mechanisms for pathogenesis on a genome scale have been undertaken [5]. Understanding the precise molecular mechanisms of infection will facilitate design of novel control strategies.The process of M. oryzae infection starts when a conidium lands on the rice leaf surface. After germination by hydration, an appressorium develops at the tip of the germ tube, from which a penetration peg emerges to penetrate the cuticle layer into the rice c
Systematic and searchable classification of cytochrome P450 proteins encoded by fungal and oomycete genomes
Moktali Venkatesh,Park Jongsun,Fedorova-Abrams Natalie D,Park Bongsoo
BMC Genomics , 2012, DOI: 10.1186/1471-2164-13-525
Abstract: Background Cytochrome P450 proteins (CYPs) play diverse and pivotal roles in fungal metabolism and adaptation to specific ecological niches. Fungal genomes encode extremely variable “CYPomes” ranging from one to more than 300 CYPs. Despite the rapid growth of sequenced fungal and oomycete genomes and the resulting influx of predicted CYPs, the vast majority of CYPs remain functionally uncharacterized. To facilitate the curation and functional and evolutionary studies of CYPs, we previously developed Fungal Cytochrome P450 Database (FCPD), which included CYPs from 70 fungal and oomycete species. Here we present a new version of FCPD (1.2) with more data and an improved classification scheme. Results The new database contains 22,940 CYPs from 213 species divided into 2,579 clusters and 115 clans. By optimizing the clustering pipeline, we were able to uncover 36 novel clans and to assign 153 orphan CYP families to specific clans. To augment their functional annotation, CYP clusters were mapped to David Nelson’s P450 databases, which archive a total of 12,500 manually curated CYPs. Additionally, over 150 clusters were functionally classified based on sequence similarity to experimentally characterized CYPs. Comparative analysis of fungal and oomycete CYPomes revealed cases of both extreme expansion and contraction. The most dramatic expansions in fungi were observed in clans CYP58 and CYP68 (Pezizomycotina), clans CYP5150 and CYP63 (Agaricomycotina), and family CYP509 (Mucoromycotina). Although much of the extraordinary diversity of the pan-fungal CYPome can be attributed to gene duplication and adaptive divergence, our analysis also suggests a few potential horizontal gene transfer events. Updated families and clans can be accessed through the new version of the FCPD database. Conclusions FCPD version 1.2 provides a systematic and searchable catalogue of 9,550 fungal CYP sequences (292 families) encoded by 108 fungal species and 147 CYP sequences (9 families) encoded by five oomycete species. In comparison to the first version, it offers a more comprehensive clan classification, is fully compatible with Nelson’s P450 databases, and has expanded functional categorization. These features will facilitate functional annotation and classification of CYPs encoded by newly sequenced fungal and oomycete genomes. Additionally, the classification system will aid in studying the roles of CYPs in the evolution of fungal adaptation to specific ecological niches.
Fungal cytochrome P450 database
Jongsun Park, Seungmin Lee, Jaeyoung Choi, Kyohun Ahn, Bongsoo Park, Jaejin Park, Seogchan Kang, Yong-Hwan Lee
BMC Genomics , 2008, DOI: 10.1186/1471-2164-9-402
Abstract: The Fungal Cytochrome P450 Database (FCPD) archives genes encoding P450s in the genomes of 66 fungal and 4 oomycete species (4,538 in total) and supports analyses of their sequences, chromosomal distribution pattern, and evolutionary histories and relationships. The archived P450s were classified into 16 classes based on InterPro terms and clustered into 141 groups using tribe-MCL. The proportion of P450s in the total proteome and class distribution in individual species exhibited certain taxon-specific characteristics.The FCPD will facilitate systematic identification and multifaceted analyses of P450s at multiple taxon levels via the web. All data and functions are available at the web site http://p450.riceblast.snu.ac.kr/ webcite.Cytochrome P450 is the collective name for a super family of heme-containing monooxygenases. P450 enzymes not only participate in the production of diverse metabolites but also play critical roles in organism's adaptation to specific ecological and/or nutritional niches by modifying potentially harmful environmental chemicals. In fungi, P450 enzymes have contributed to exploration of and adaptation to diverse ecological niches [1,2].Rapidly accumulating genome sequences from diverse fungal species, including more than 80 species with more currently being sequenced [3], offer opportunities to study the genetic and evolutionary mechanisms underpinning different fungal life styles at the genome level [4-7]. To support such studies with the focus on cytochrome P450s, we constructed a new platform named as the Fungal Cytochrome P450 Database (FCPD), which archives P450s in most sequenced fungal and oomycetes species and allows comparison of the archived data with previously published datasets, such as the Cytochrome P450 Engineering Database [8], a manually curated P450 database at http://drnelson.utmem.edu/CytochromeP450.html webcite (referred as the Nelson's P450 database herein), and P450 datasets derived from extensive phylogenetic analys
Fungal Secretome Database: Integrated platform for annotation of fungal secretomes
Jaeyoung Choi, Jongsun Park, Donghan Kim, Kyongyong Jung, Seogchan Kang, Yong-Hwan Lee
BMC Genomics , 2010, DOI: 10.1186/1471-2164-11-105
Abstract: A three-layer hierarchical identification rule based on nine prediction programs was used to identify putative secretory proteins in 158 fungal/oomycete genomes (208,883 proteins, 15.21% of the total proteome). The presence of putative effectors containing known host targeting signals such as RXLX [EDQ] and RXLR was investigated, presenting the degree of bias along with the species. The FSD's user-friendly interface provides summaries of prediction results and diverse web-based analysis functions through Favorite, a personalized repository.The FSD can serve as an integrated platform supporting researches on secretory proteins in the fungal kingdom. All data and functions described in this study can be accessed on the FSD web site at http://fsd.snu.ac.kr/ webcite.The "secretome" refers to the collection of proteins that contain a signal peptide and are processed via the endoplasmic reticulum and Golgi apparatus before secretion [1]. In organisms from bacteria to humans, secretory proteins are common and perform diverse functions. These functions include immune system [2], roles as neurotransmitters in the nervous system [3], roles as hormones/pheromones [4], acquisition of nutrients [5-7], building and remodeling of cell walls [8], signaling and environmental sensing [9], and competition with other organisms [10-13]. Some secretory proteins in pathogens function as effectors that manipulate and/or destroy host cells with special signatures. In Plasmodium and Phytophthora species, effectors carry the RXLX [EDQ] or RXLR motifs as host targeting signals [11-13].With the aid of advanced genome sequencing technologies [14], the rapid increase of sequenced fungal genomes offers many opportunities to study the function and evolution of secretory proteins at the genome level [15,16]. The Comparative Fungal Genomics Platform (CFGP; http://cfgp.snu.ac.kr/ webcite) [16] now archives 235 genomes from 120 fungal/oomycete species. The accurate prediction of secretory proteins in s
Silver nanoparticles inhibit VEGF-and IL-1β-induced vascular permeability via Src dependent pathway in porcine retinal endothelial cells
Sardarpasha Sheikpranbabu, Kalimuthu Kalishwaralal, Deepak Venkataraman, Soo Eom, Jongsun Park, Sangiliyandi Gurunathan
Journal of Nanobiotechnology , 2009, DOI: 10.1186/1477-3155-7-8
Abstract: Vascular endothelial barrier dysfunction occurs in a large number of disease processes including diabetic retinopathy, stroke, pulmonary edema, myocardial infarction, inflammatory bowel disease, nephropathies, rheumatoid arthritis, and tumours. In these diseases, increased vascular permeability is associated with elevated levels of either one or more growth factors or cytokines [1]. Vascular endothelial growth factor (VEGF) has received considerable attention as a tumour-secreted vascular permeability factor [2,3]. VEGF is determined to posses 50,000 times more potency than histamine in inducing vasopermeability in the dermal vasculature. Previous reports indicate the correlation between the increases in permeability in ischemic retinopathies and possibly also in exudative macular degeneration and uveitis and the increased VEGF levels [4-7]. In fact, VEGF antagonists have been successfully used to reduce retinal/macular edema in neovascular eye diseases such as age-related macular degeneration with stabilization or even improvement of visual acuity in a subset of affected patients [8]. Although VEGF is thought to play a major role in stimulating vascular permeability, this process undoubtedly involves multiple other factors as well, including inflammatory cytokines such as interleukin-1beta (IL-1β) [9]. Previously IL-1β was shown to induce the permeability through the vasculature of the blood retinal barrier in rats [10].Now a great deal of research is focused on the development of inhibitors for vascular permeability. In fields like drug delivery, imaging and diagnosis & treatment of cancer various nanoparticles are proposed to function as a tool [11,12]. Furthermore, currently efforts are being made to investigate the use of nanomaterials in various therapeutic applications, where the nanoparticles could be the active component or could just be the physical support for the functional moieties. In addition, the importance of augmenting the performance of convention
The PEX7-Mediated Peroxisomal Import System Is Required for Fungal Development and Pathogenicity in Magnaporthe oryzae
Jaeduk Goh, Junhyun Jeon, Kyoung Su Kim, Jongsun Park, Sook-Young Park, Yong-Hwan Lee
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0028220
Abstract: In eukaryotes, microbodies called peroxisomes play important roles in cellular activities during the life cycle. Previous studies indicate that peroxisomal functions are important for plant infection in many phytopathogenic fungi, but detailed relationships between fungal pathogenicity and peroxisomal function still remain unclear. Here we report the importance of peroxisomal protein import through PTS2 (Peroxisomal Targeting Signal 2) in fungal development and pathogenicity of Magnaporthe oryzae. Using an Agrobacterium tumefaciens-mediated transformation library, a pathogenicity-defective mutant was isolated from M. oryzae and identified as a T-DNA insert in the PTS2 receptor gene, MoPEX7. Gene disruption of MoPEX7 abolished peroxisomal localization of a thiolase (MoTHL1) containing PTS2, supporting its role in the peroxisomal protein import machinery. ΔMopex7 showed significantly reduced mycelial growth on media containing short-chain fatty acids as a sole carbon source. ΔMopex7 produced fewer conidiophores and conidia, but conidial germination was normal. Conidia of ΔMopex7 were able to develop appressoria, but failed to cause disease in plant cells, except after wound inoculation. Appressoria formed by ΔMopex7 showed a defect in turgor generation due to a delay in lipid degradation and increased cell wall porosity during maturation. Taken together, our results suggest that the MoPEX7-mediated peroxisomal matrix protein import system is required for fungal development and pathogenicity M. oryzae.
Combining ChIP-chip and Expression Profiling to Model the MoCRZ1 Mediated Circuit for Ca2+/Calcineurin Signaling in the Rice Blast Fungus
Soonok Kim,Jinnan Hu,Yeonyee Oh,Jongsun Park,Jinhee Choi,Yong-Hwan Lee,Ralph A. Dean,Thomas K. Mitchell
PLOS Pathogens , 2010, DOI: 10.1371/journal.ppat.1000909
Abstract: Significant progress has been made in defining the central signaling networks in many organisms, but collectively we know little about the downstream targets of these networks and the genes they regulate. To reconstruct the regulatory circuit of calcineurin signal transduction via MoCRZ1, a Magnaporthe oryzae C2H2 transcription factor activated by calcineurin dephosphorylation, we used a combined approach of chromatin immunoprecipitation - chip (ChIP-chip), coupled with microarray expression studies. One hundred forty genes were identified as being both a direct target of MoCRZ1 and having expression concurrently differentially regulated in a calcium/calcineurin/MoCRZ1 dependent manner. Highly represented were genes involved in calcium signaling, small molecule transport, ion homeostasis, cell wall synthesis/maintenance, and fungal virulence. Of particular note, genes involved in vesicle mediated secretion necessary for establishing host associations, were also found. MoCRZ1 itself was a target, suggesting a previously unreported autoregulation control point. The data also implicated a previously unreported feedback regulation mechanism of calcineurin activity. We propose that calcium/calcineurin regulated signal transduction circuits controlling development and pathogenicity manifest through multiple layers of regulation. We present results from the ChIP-chip and expression analysis along with a refined model of calcium/calcineurin signaling in this important plant pathogen.
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