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Leucine rich repeate kinase

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https://www.readbyqxmd.com/read/29137139/deduction-of-novel-genes-potentially-involved-in-osteoblasts-of-rheumatoid-arthritis-using-next-generation-sequencing-and-bioinformatic-approaches
#1
Yi-Jen Chen, Wei-An Chang, Ya-Ling Hsu, Chia-Hsin Chen, Po-Lin Kuo
The role of osteoblasts in peri-articular bone loss and bone erosion in rheumatoid arthritis (RA) has gained much attention, and microRNAs are hypothesized to play critical roles in the regulation of osteoblast function in RA. The aim of this study is to explore novel microRNAs differentially expressed in RA osteoblasts and to identify genes potentially involved in the dysregulated bone homeostasis in RA. RNAs were extracted from cultured normal and RA osteoblasts for sequencing. Using the next generation sequencing and bioinformatics approaches, we identified 35 differentially expressed microRNAs and 13 differentially expressed genes with potential microRNA-mRNA interactions in RA osteoblasts...
November 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29129681/decreased-sirtuin-deacetylase-activity-in-lrrk2-g2019s-ipsc-derived-dopaminergic-neurons
#2
Andrew J Schwab, Samantha L Sison, Michael R Meade, Katarzyna A Broniowska, John A Corbett, Allison D Ebert
Mitochondrial changes have long been implicated in the pathogenesis of Parkinson's disease (PD). The glycine to serine mutation (G2019S) in leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause for PD and has been shown to impair mitochondrial function and morphology in multiple model systems. We analyzed mitochondrial function in LRRK2 G2019S induced pluripotent stem cell (iPSC)-derived neurons to determine whether the G2019S mutation elicits similar mitochondrial deficits among central and peripheral nervous system neuron subtypes...
October 31, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29127874/generation-of-induced-pluripotent-stem-cells-from-a-patient-with-parkinson-s-disease-carrying-lrrk2-p-i2012t-mutation
#3
Chin-Hsien Lin, Yu-Che Cheng, Han-I Lin, Ming-Ching Ho, Yu-Hung Hsu, Cheng-Hao Wen, Hui-Wen Ko, Huai-En Lu, Ching-Ying Huang, Patrick C H Hsieh
Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by interactions between genetic and environmental factors. Leucine rich repeat kinase (LRRK2) is the most prevalent mutation in autosomal-dominant inheritance of PD. Here, we generated induced pluripotent stem cells (iPSCs) from the peripheral blood mononuclear cells of a female patient with p.I2012T mutation in LRRK2 gene by using the Sendai-virus delivery system. The resulting iPSCs had a normal karyotype. The iPSCs also showed pluripotency confirmed by immunofluorescent staining and differentiated into the 3 germ layers in vivo...
October 31, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29116064/-identification-and-expression-analysis-of-receptor-like-kinase-gene-erecta-in-mycoheterotrophic-plant-monotropa-hypopitys
#4
A V Shchennikova, E Z Kochieva, A V Beletsky, M A Filyushin, O A Shulga, N V Ravin, K G Skryabin
The precise spatial-temporal coordination of cell division and differentiation is necessary for the correct formation of tissues, organs, and the organism as a whole. This coordination has been implemented by the intercellular communication mediated by signaling molecules and receptors that selectively recognize them. Membrane receptor kinases of ERECTA family regulate inflorescence and flower structure, the formation of root epidermis and adaptation responses. The characterization of the ERECTA genes of flowering plant pinesap Monotropa hypopitys with unique development features can enrich the knowledge about the kinase ERECTA functions and conserved development processes with their participation...
September 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/29109411/structural-basis-for-receptor-recognition-of-pollen-tube-attraction-peptides
#5
Xiaoxiao Zhang, Weijia Liu, Takuya T Nagae, Hidenori Takeuchi, Heqiao Zhang, Zhifu Han, Tetsuya Higashiyama, Jijie Chai
Transportation of the immobile sperms directed by pollen tubes to the ovule-enclosed female gametophytes is important for plant sexual reproduction. The defensin-like (DEFL) cysteine-rich peptides (CRPs) LUREs play an essential role in pollen tube attraction to the ovule, though their receptors still remain controversial. Here we provide several lines of biochemical evidence showing that the extracellular domain of the leucine-rich repeat receptor kinase (LRR-RK) PRK6 from Arabidopsis thaliana directly interacts with AtLURE1 peptides...
November 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29093216/the-coiled-coil-and-nucleotide-binding-domains-of-brown-planthopper-resistance14-function-in-signaling-and-resistance-against-planthopper-in-rice
#6
Liang Hu, Yan Wu, Di Wu, Weiwei Rao, Jianping Guo, Yinhua Ma, Zhizheng Wang, Xinxin Shangguan, Huiying Wang, Chunxue Xu, Jin Huang, Shaojie Shi, Rongzhi Chen, Bo Du, Lili Zhu, Guangcun He
BROWN PLANTHOPPER RESISTANCE14 (BPH14), the first planthopper-resistance gene isolated via map-based cloning in rice (Oryza sativa), encodes a coiled-coil-, nucleotide-binding site-, leucine-rich repeat (CC-NB-LRR) protein. Several planthopper and aphid resistance genes encoding proteins with similar structures have recently been identified. Here, we analyzed the functions of the domains of BPH14 to identify molecular mechanisms underpinning BPH14-mediated planthopper resistance. The CC or NB domains alone or in combination (CC-NB [CN]) conferred a similar level of brown planthopper resistance to that of full-length (FL) BPH14...
November 1, 2017: Plant Cell
https://www.readbyqxmd.com/read/29038245/mitochondrial-calcium-dysregulation-contributes-to-dendrite-degeneration-mediated-by-pd-lbd-associated-lrrk2-mutants
#7
Manish Verma, Jason Callio, P Anthony Otero, Israel Sekler, Zachary P Wills, Charleen T Chu
Mutations in leucine-rich repeat kinase 2 (LRRK2) contribute to development of late-onset familial Parkinson's disease (PD), with clinical features of motor and cognitive dysfunction indistinguishable from sporadic PD. Calcium dysregulation plays an important role in PD pathogenesis, but the mechanisms of neurodegeneration remain unclear. Recent reports indicate enhanced excitatory neurotransmission in cortical neurons expressing mutant LRRK2, which occurs prior to the well-characterized phenotype of dendritic shortening...
October 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29037452/balancing-immunity-and-yield-in-crop-plants
#8
REVIEW
Yuese Ning, Wende Liu, Guo-Liang Wang
Crop diseases cause enormous yield losses and threaten global food[ED1] security. The use of highly resistant cultivars can effectively control plant diseases, but in crops, genetic immunity to disease often comes with an unintended reduction in growth and yield. Here, we review recent advances in understanding how nucleotide-binding domain, leucine-rich repeat (NLR) receptors and cell wall-associated kinase (WAK) proteins function in balancing immunity and yield. We also discuss the role of plant hormones and transcription factors in regulating the trade-offs between plant growth and immunity...
October 13, 2017: Trends in Plant Science
https://www.readbyqxmd.com/read/29033963/convergent-evolution-of-pathogen-effectors-toward-reactive-oxygen-species-signaling-networks-in-plants
#9
REVIEW
Nam-Soo Jwa, Byung Kook Hwang
Microbial pathogens have evolved protein effectors to promote virulence and cause disease in host plants. Pathogen effectors delivered into plant cells suppress plant immune responses and modulate host metabolism to support the infection processes of pathogens. Reactive oxygen species (ROS) act as cellular signaling molecules to trigger plant immune responses, such as pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity. In this review, we discuss recent insights into the molecular functions of pathogen effectors that target multiple steps in the ROS signaling pathway in plants...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29023112/design-of-leucine-rich-repeat-kinase-2-lrrk2-inhibitors-using-a-crystallographic-surrogate-derived-from-checkpoint-kinase-1-chk1
#10
Douglas S Williamson, Garrick P Smith, Pamela Acheson-Dossang, Simon T Bedford, Victoria Chell, I-Jen Chen, Justus C A Daechsel, Zoe Daniels, Laurent David, Pawel Dokurno, Morten Hentzer, Martin C Herzig, Roderick E Hubbard, Jonathan D Moore, James B Murray, Samantha Newland, Stuart C Ray, Terry Shaw, Allan E Surgenor, Lindsey Terry, Kenneth Thirstrup, Yikang Wang, Kenneth V Christensen
Mutations in leucine-rich repeat kinase 2 (LRRK2), such as G2019S, are associated with an increased risk of developing Parkinson's disease. Surrogates for the LRRK2 kinase domain based on checkpoint kinase 1 (CHK1) mutants were designed, expressed in insect cells infected with baculovirus, purified, and crystallized. X-ray structures of the surrogates complexed with known LRRK2 inhibitors rationalized compound potency and selectivity. The CHK1 10-point mutant was preferred, following assessment of surrogate binding affinity with LRRK2 inhibitors...
October 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29021806/erecta-regulates-cell-elongation-by-activating-auxin-biosynthesis-in-arabidopsis-thaliana
#11
Xiaoya Qu, Zhong Zhao, Zhaoxia Tian
The ERECTA family genes, ERECTA (ER), ERECTA-LIKE1 (ERL1), and ERECTA-LIKE2 (ERL2), encode leucine-rich repeat receptor-like kinases in Arabidopsis thaliana. Knocking out these three genes can cause severe phenotypes, which indicates that they play significant roles in plant growth and development. However, the molecular mechanism within remains unclear. Here we show that the short hypocotyl phenotypes of er erl1 erl2 mutants are mainly due to the defects of cell elongation rather than the cell division. In contrast, in the ERECTA overexpression transgenic plants, the hypocotyl length is increased with elongated cells...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29017442/genome-wide-characterization-evolution-and-expression-analysis-of-the-leucine-rich-repeat-receptor-like-protein-kinase-lrr-rlk-gene-family-in-rosaceae-genomes
#12
Jiangmei Sun, Leiting Li, Peng Wang, Shaoling Zhang, Juyou Wu
BACKGROUND: Leucine-rich repeat receptor-like protein kinase (LRR-RLK) is the largest gene family of receptor-like protein kinases (RLKs) and actively participates in regulating the growth, development, signal transduction, immunity, and stress responses of plants. However, the patterns of LRR-RLK gene family evolution in the five main Rosaceae species for which genome sequences are available have not yet been reported. In this study, we performed a comprehensive analysis of LRR-RLK genes for five Rosaceae species: Fragaria vesca (strawberry), Malus domestica (apple), Pyrus bretschneideri (Chinese white pear), Prunus mume (mei), and Prunus persica (peach), which contained 201, 244, 427, 267, and 258 LRR-RLK genes, respectively...
October 10, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28985749/correction-to-leucine-rich-repeat-kinase-2-lrrk2-phosphorylates-p53-and-induces-p21-waf1-cip1-expression
#13
Dong Hwan Ho, Hyejung Kim, Jisun Kim, Hyuna Sim, Hyunjun Ahn, Janghwan Kim, Hyemyung Seo, Kwang Chul Chung, Bum-Joon Park, Ilhong Son, Wongi Seol
No abstract text is available yet for this article.
October 6, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28973664/lrrk2-g2019s-induced-mitochondrial-dna-damage-is-lrrk2-kinase-dependent-and-inhibition-restores-mtdna-integrity-in-parkinson-s-disease
#14
Evan H Howlett, Nicholas Jensen, Frances Belmonte, Faria Zafar, Xiaoping Hu, Jillian Kluss, Birgitt Schüle, Brett A Kaufman, J T Greenamyre, Laurie H Sanders
Mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with increased risk for developing Parkinson's disease (PD). Previously, we found that LRRK2 G2019S mutation carriers have increased mitochondrial DNA (mtDNA) damage and after zinc finger nuclease-mediated gene mutation correction, mtDNA damage was no longer detectable. While the mtDNA damage phenotype can be unambiguously attributed to the LRRK2 G2019S mutation, the underlying mechanism(s) is unknown. Here, we examine the role of LRRK2 kinase function in LRRK2 G2019S-mediated mtDNA damage, using both genetic and pharmacological approaches in cultured neurons and PD patient-derived cells...
November 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28973420/lrrk2-interacts-with-atm-and-regulates-mdm2-p53-cell-proliferation-axis-in-response-to-genotoxic-stress
#15
Zhongcan Chen, Zhen Cao, Wei Zhang, Minxia Gu, Zhi Dong Zhou, Baojie Li, Jing Li, Eng King Tan, Li Zeng
Pathogenic leucine-rich repeat kinase 2 (LRRK2) mutations are recognized as the most common cause of familial Parkinson's disease in certain populations. Recently, LRRK2 mutations were shown to be associated with a higher risk of hormone-related cancers. However, how LRRK2 itself contributes to cancer risk remains unknown. DNA damage causes cancer, and DNA damage responses are among the most important pathways in cancer biology. To understand the role of LRRK2 in DNA damage response pathway, we induced DNA damage by applying genotoxic stress to the cells with Adriamycin...
November 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28972154/neutrophil-microparticle-production-and-inflammasome-activation-by-hyperglycemia-due-to-cytoskeletal-instability
#16
Stephen R Thom, Veena M Bhopale, Kevin Yu, Weiliang Huang, Maureen A Kane, David J Margolis
Microparticles are lipid bilayer-enclosed vesicles produced by cells under oxidative stress. MP production is elevated in patients with diabetes, but the underlying cellular mechanisms are poorly understood. We hypothesized that raising glucose above the physiological level of 5.5 mm would stimulate leukocytes to produce MPs and activate the nucleotide-binding domain, leucine-rich repeat pyrin domain-containing 3 (NLRP3) inflammasome. We found that when incubated in buffer with up to 20 mm glucose, human and murine neutrophils, but not monocytes, generate progressively more MPs with high interleukin (IL)-1β content...
November 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28972042/transmembrane-and-coiled-coil-domain-1-impairs-the-akt-signaling-pathway-in-urinary-bladder-urothelial-carcinoma-a-characterization-of-a-tumor-suppressor
#17
Chien-Feng Li, Wen-Ren Wu, Ti-Chun Chan, Yu-Hui Wang, Lih-Ren Chen, Wen-Jeng Wu, Bi-Wen Yeh, Shih-Shin Liang, Yow-Ling Shiue
PURPOSE: Urinary bladder urothelial carcinoma (UBUC) is a common malignant disease in developed countries. Cell cycle dysregulation resulting in uncontrolled cell proliferation has been associated with UBUC development. This study aimed to explore the roles of TMCO1 in UBUCs. EXPERIMENTAL DESIGN: Data mining, branched DNA assay, immunohistochemistry, xenograft, cell culture, quantitative RT-PCR, immunoblotting, stable and transient transfection, lentivirus production and stable knockdown, cell cycle, cell viability and proliferation, soft agar, wound healing, transwell migration and invasion, co-immunoprecipitation, immunocytochemistry, AKT serine/threonine kinase (AKT) activity assays and site-directed mutagenesis were used to study TMCO1 involvement in vivo and in vitro...
September 29, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28967880/nlrx1-promotes-immediate-irf1-directed-antiviral-responses-by-limiting-dsrna-activated-translational-inhibition-mediated-by-pkr
#18
Hui Feng, Erik M Lenarcic, Daisuke Yamane, Eliane Wauthier, Jinyao Mo, Haitao Guo, David R McGivern, Olga González-López, Ichiro Misumi, Lola M Reid, Jason K Whitmire, Jenny P-Y Ting, Joseph A Duncan, Nathaniel J Moorman, Stanley M Lemon
NLRX1 is unique among the nucleotide-binding-domain and leucine-rich-repeat (NLR) proteins in its mitochondrial localization and ability to negatively regulate antiviral innate immunity dependent on the adaptors MAVS and STING. However, some studies have suggested a positive regulatory role for NLRX1 in inducing antiviral responses. We found that NLRX1 exerted opposing regulatory effects on viral activation of the transcription factors IRF1 and IRF3, which might potentially explain such contradictory results...
October 2, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28958936/suppression-of-neuroinflammation-by-matrix-metalloproteinase-8-inhibitor-in-aged-normal-and-lrrk2-g2019s-parkinson-s-disease-model-mice-challenged-with-lipopolysaccharide
#19
Jisun Kim, Yeon-Hui Jeong, Eun-Jung Lee, Jin-Sun Park, Hyemyung Seo, Hee-Sun Kim
Microglial priming is caused by aging and neurodegenerative diseases, and is characterized by an exaggerated microglial inflammatory response to secondary and sub-threshold challenges. In the present study, we examined the effects of the matrix metalloproteinase-8 (MMP-8) inhibitor (M8I) on the brain of aged normal and leucine-rich repeat kinase 2 (LRRK2) G2019S Parkinson's disease (PD) model mice systemically stimulated with lipopolysaccharide (LPS). The results indicated that Iba-1 positive microglia and GFAP-positive astrocytes, which were increased by LPS, significantly decreased by M8I in aged normal and PD model mice...
November 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28941828/fatigue-correlates-with-lrrk2-g2385r-variant-in-chinese-parkinson-s-disease-patients
#20
Rao Fu, Shi-Shuang Cui, Juan-Juan Du, Ya-Chao He, Chao Gao, Pei Huang, Yi-Wei Qian, Xiao-Guang Luo, Sheng-Di Chen
INTRODUCTION: Fatigue is common in patients with Parkinson's disease (PD). The leucine-rich repeat kinase 2 (LRRK2) G2385R variant predisposes individuals to develop PD in China. The aim of this study was to evaluate whether the LRRK2 G2385R variant is associated with fatigue in patients with PD. METHODS: Fatigue was evaluated by the Parkinson Fatigue Scale (PFS) in 329 PD patients and 180 controls, a cut-off score of ≥3.3 was used to define the presence of fatigue...
September 18, 2017: Parkinsonism & related Disorders
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