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https://www.readbyqxmd.com/read/29025973/dynamic-multi-site-phosphorylation-by-fyn-and-abl-drives-the-interaction-between-crkl-and-the-novel-scaffolding-receptors-dcbld1-and-dcbld2
#1
Anna M Schmoker, Jaye L Weinert, Kyle J Kellett, Hannah E Johnson, Ryan M Joy, Marion E Weir, Alicia M Ebert, Bryan A Ballif
Discoidin, CUB, and LCCL Domain-containing (DCBLD) 2 is a neuropilin-like transmembrane scaffolding receptor with known and anticipated roles in vascular remodeling and neuronal positioning. DCBLD2 is also upregulated in several cancers and can drive glioblastomas downstream of activated Epidermal Growth Factor Receptor. While a few studies have shown either a positive or negative role for DCBLD2 in regulating growth factor receptor signaling, little is known about the conserved signaling features of DCBLD family members that drive their molecular activities...
October 12, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29022003/data-on-the-effect-of-knockout-of-cytohesin-1-in-myelination-related-protein-kinase-signaling
#2
Ruri Tsuneishi, Naoto Matsumoto, Misa Itaoka, Yuri Urai, Minami Kaneko, Natsumi Watanabe, Shou Takashima, Yoichi Seki, Takako Morimoto, Hiroyuki Sakagami, Yuki Miyamoto, Junji Yamauchi
Cytohesin-1 is the guanine-nucleotide exchange factor of Arf6, a small GTPase of Arf family, and participates in cellular morphological changes. Knockout mice of cytohesin-1 exhibit decreased myelination of neuronal axons in the peripheral nervous system (PNS) "Phosphorylation of cytohesin-1 by Fyn is required for initiation of myelination and the extent of myelination during development (Yamauchi et al., 2012) [1]". Herein we provide the data regarding decreased phosphorylation levels of protein kinases involved in two major myelination-related kinase cascades in cytohesin-1 knockout mice...
December 2017: Data in Brief
https://www.readbyqxmd.com/read/29021832/pharmacogenomics-in-the-treatment-of-mood-disorders-strategies-and-opportunities-for-personalized-psychiatry
#3
REVIEW
Azmeraw T Amare, Klaus Oliver Schubert, Bernhard T Baune
Personalized medicine (personalized psychiatry in a specific setting) is a new model towards individualized care, in which knowledge from genomics and other omic pillars (microbiome, epigenomes, proteome, and metabolome) will be combined with clinical data to guide efforts to new drug development and targeted prescription of the existing treatment options. In this review, we summarize pharmacogenomic studies in mood disorders that may lay the foundation towards personalized psychiatry. In addition, we have discussed the possible strategies to integrate data from omic pillars as a future path to personalized psychiatry...
September 2017: EPMA Journal
https://www.readbyqxmd.com/read/28993142/ghrelin-upregulates-the-phosphorylation-of-the-glun2b-subunit-of-the-nmda-receptor-by-activating-ghsr1a-and-fyn-in-the-rat-hippocampus
#4
Liza Berrout, Masako Isokawa
Ghrelin and its receptor GHSR1a have been shown to exert numerous physiological functions in the brain, in addition to the well-established orexigenic role in the hypothalamus. Earlier work indicated that ghrelin stimulated the phosphorylation of the GluN1 subunit of the NMDA receptor (NMDAR) and enhanced synaptic transmission in the hippocampus. In the present study, we report that the exogenous application of ghrelin increased GluN2B phosphorylation. This increase was independent of GluN2B subunit activity or NMDAR channel activity...
October 6, 2017: Brain Research
https://www.readbyqxmd.com/read/28990106/identification-of-key-genes-for-diabetic-kidney-disease-using-biological-informatics-methods
#5
Fuzhe Ma, Tao Sun, Meiyan Wu, Wanning Wang, Zhonggao Xu
Diabetic kidney disease (DKD) is a common complication of diabetes, which is characterized by albuminuria, impaired glomerular filtration rate or a combination of the two. The aim of the present study was to identify the potential key genes involved in DKD progression and to subsequently investigate the underlying mechanism involved in DKD development. The array data of GSE30528 including 9 DKD and 13 control samples was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) in DKD glomerular and tubular kidney biopsy tissues were compared with normal tissues, and were analyzed using the limma package...
September 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28978570/enhancer-profiling-identifies-critical-cancer-genes-and-characterizes-cell-identity-in-adult-t-cell-leukemia
#6
Regina Wan Ju Wong, Phuong Cao Thi Ngoc, Wei Zhong Leong, Alice Wei Yee Yam, Tinghu Zhang, Kaori Asamitsu, Shinsuke Iida, Takashi Okamoto, Ryuzo Ueda, Nathanael S Gray, Takashi Ishida, Takaomi Sanda
A number of studies have recently demonstrated that "super-enhancers", which are large cluster of enhancers typically marked by a high level of acetylation of histone H3 lysine 27 and mediator bindings, are frequently associated with genes that control and define cell identity during normal development. Super-enhancers are also often enriched at cancer genes in various malignancies. Identification of such enhancers would pinpoint critical factors that directly contribute to pathogenesis. Here, we performed enhancer profiling using primary leukemia samples from adult T-cell leukemia/lymphoma (ATL), which is a genetically heterogeneous intractable cancer...
October 4, 2017: Blood
https://www.readbyqxmd.com/read/28955330/perturbation-of-b-cell-gene-expression-persists-in-hiv-infected-children-despite-effective-antiretroviral-therapy-and-predicts-h1n1-response
#7
Nicola Cotugno, Lesley De Armas, Suresh Pallikkuth, Stefano Rinaldi, Biju Issac, Alberto Cagigi, Paolo Rossi, Paolo Palma, Savita Pahwa
Despite effective antiretroviral therapy (ART), HIV-infected individuals with apparently similar clinical and immunological characteristics can vary in responsiveness to vaccinations. However, molecular mechanisms responsible for such impairment, as well as biomarkers able to predict vaccine responsiveness in HIV-infected children, remain unknown. Following the hypothesis that a B cell qualitative impairment persists in HIV-infected children (HIV) despite effective ART and phenotypic B cell immune reconstitution, the aim of the current study was to investigate B cell gene expression of HIV compared to age-matched healthy controls (HCs) and to determine whether distinct gene expression patterns could predict the ability to respond to influenza vaccine...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28951880/chinese-herbal-formula-modified-danggui-buxue-tang-attenuates-apoptosis-of-hematopoietic-stem-cells-in-immune-mediated-aplastic-anemia-mouse-model
#8
Jingwei Zhou, Xue Li, Peiying Deng, Yi Wei, Juan Liu, Meng Chen, Yamei Xu, Dongmei Zhang, Lingqun Zhu, Lixia Lou, Bin Dong, Qiushuo Jin, Limin Chai
A derivative formula, DGBX, which is composed of three herbs (Radix astragali, Radix Angelicae sinensis, and Coptis chinensis Franch), is derived from a famous Chinese herbal formula, Danggui Buxue Tang (DBT) (Radix astragali and Radix Angelicae sinensis). We aimed to investigate the effects of DGBX on the regulation of the balance between proliferation and apoptosis of hematopoietic stem cells (HSCs) due to the aberrant immune response in a mouse model of aplastic anemia (AA). Cyclosporine (CsA), an immunosuppressor, was used as the positive control...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28948209/an-essential-role-of-fyn-in-the-modulation-of-metabotropic-glutamate-receptor-1-in-neurons
#9
Dao-Zhong Jin, Li-Min Mao, John Q Wang
Fyn is a member of the Src family of nonreceptor tyrosine kinases and is broadly expressed in the CNS. As a synapse-enriched kinase, Fyn interacts with and phosphorylates local substrates to regulate synaptic transmission and plasticity, although our knowledge of specific targets of Fyn at synaptic sites remains incomplete and the accurate role of Fyn in regulating synaptic proteins is poorly understood. In this study, we initiated an effort to explore the interaction of Fyn with a metabotropic glutamate receptor (mGluR)...
July 2017: ENeuro
https://www.readbyqxmd.com/read/28945221/%C3%AE-synuclein-interacts-with-prp-c-to-induce-cognitive-impairment-through-mglur5-and-nmdar2b
#10
Diana G Ferreira, Mariana Temido-Ferreira, Hugo Vicente Miranda, Vânia L Batalha, Joana E Coelho, Éva M Szegö, Inês Marques-Morgado, Sandra H Vaz, Jeong Seop Rhee, Matthias Schmitz, Inga Zerr, Luísa V Lopes, Tiago F Outeiro
Synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies, are neurodegenerative disorders that are characterized by the accumulation of α-synuclein (aSyn) in intracellular inclusions known as Lewy bodies. Prefibrillar soluble aSyn oligomers, rather than larger inclusions, are currently considered to be crucial species underlying synaptic dysfunction. We identified the cellular prion protein (PrP(C)) as a key mediator in aSyn-induced synaptic impairment. The aSyn-associated impairment of long-term potentiation was blocked in Prnp null mice and rescued following PrP(C) blockade...
September 25, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28944885/exploring-the-key-genes-and-pathways-of-osteosarcoma-with-pulmonary-metastasis-using-a-gene-expression-microarray
#11
Zhongju Shi, Hengxing Zhou, Bin Pan, Lu Lu, Zhijian Wei, Linlin Shi, Xue Yao, Yi Kang, Shiqing Feng
Osteosarcoma is a common and highly malignant tumour in children and teenagers that is characterized by drug resistance and high metastatic potential. Patients often develop pulmonary metastasis and have a low survival rate. However, the mechanistic basis for pulmonary metastasis remains unclear. To identify key gene and pathways associated with pulmonary metastasis of osteosarcoma, the authors downloaded the gene expression dataset GSE85537 and obtained the differentially expressed genes (DEGs) by analyzing high‑throughput gene expression in primary tumours and lung metastases...
September 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28935570/molecular-alterations-in-a-mouse-cardiac-model-of-friedreich-s-ataxia-an-impaired-nrf2-response-mediated-via-up-regulation-of-keap1-and-activation-of-the-gsk3%C3%AE-axis
#12
Amy Anzovino, Shannon Chiang, Bronwyn E Brown, Clare L Hawkins, Des R Richardson, Michael L-H Huang
Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a master regulator of the anti-oxidant response. However, studies in models of Friedreich's ataxia (FA), a neuro- and cardio-degenerative disease associated with oxidative stress, reported decreased Nrf2 expression due to unknown mechanisms. Using a mouse conditional frataxin knockout (KO) model in the heart and skeletal muscle, we examined the Nrf2 pathway in these tissues. Frataxin KO results in fatal cardiomyopathy, while skeletal muscle was asymptomatic...
September 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28928455/polydatin-inhibits-mast-cell-mediated-allergic-inflammation-by-targeting-pi3k-akt-mapk-nf-%C3%AE%C2%BAb-and-nrf2-ho-1-pathways
#13
Jing Ye, Hongmei Piao, Jingzhi Jiang, Guangyu Jin, Mingyu Zheng, Jinshi Yang, Xiang Jin, Tianyi Sun, Yun Ho Choi, Liangchang Li, Guanghai Yan
Polydatin(PD) shows anti-allergic inflammatory effect, and this study investigated its underlying mechanisms in in vitro and in vivo models. IgE-mediated passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis (PSA) models were used to confirm PD effect in vivo. Various signaling pathway proteins in mast cell were examined. RT-PCR, ELISA and western blotting were applied when appropriate. Activity of Lyn and Fyn kinases in vitro was measured using the Kinase Enzyme System. PD dose-dependently reduced the pigmentation of Evans blue in the PCA model and decreased the concentration of serum histamine in PSA model, and attenuated the degranulation of mast cells without generating cytotoxicity...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28927418/a-systematic-review-and-integrative-approach-to-decode-the-common-molecular-link-between-levodopa-response-and-parkinson-s-disease
#14
Debleena Guin, Manish Kumar Mishra, Puneet Talwar, Chitra Rawat, Suman S Kushwaha, Shrikant Kukreti, Ritushree Kukreti
BACKGROUND: PD is a progressive neurodegenerative disorder commonly treated by levodopa. The findings from genetic studies on adverse effects (ADRs) and levodopa efficacy are mostly inconclusive. Here, we aim to identify predictive genetic biomarkers for levodopa response (LR) and determine common molecular link with disease susceptibility. A systematic review for LR was conducted for ADR, and drug efficacy, independently. All included articles were assessed for methodological quality on 14 parameters...
September 19, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28923922/trkb-neurotrophic-activities-are-blocked-by-%C3%AE-synuclein-triggering-dopaminergic-cell-death-in-parkinson-s-disease
#15
Seong Su Kang, Zhentao Zhang, Xia Liu, Fredric P Manfredsson, Matthew J Benskey, Xuebing Cao, Jun Xu, Yi E Sun, Keqiang Ye
BDNF/TrkB neurotrophic signaling is essential for dopaminergic neuronal survival, and the activities are reduced in the substantial nigra (SN) of Parkinson's disease (PD). However, whether α-Syn (alpha-synuclein) aggregation, a hallmark in the remaining SN neurons in PD, accounts for the neurotrophic inhibition remains elusive. Here we show that α-Syn selectively interacts with TrkB receptors and inhibits BDNF/TrkB signaling, leading to dopaminergic neuronal death. α-Syn binds to the kinase domain on TrkB, which is negatively regulated by BDNF or Fyn tyrosine kinase...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28912680/fyn-signaling-is-compartmentalized-to-dopamine-d1-receptor-expressing-neurons-in-the-dorsal-medial-striatum
#16
Khanhky Phamluong, Emmanuel Darcq, Su Wu, Samuel A Sakhai, Dorit Ron
The tyrosine kinase Fyn plays an important role in synaptic plasticity, learning, and memory. Here we report that Fyn is activated in response to 15 min D1 receptor (D1R) but not D2 receptor (D2R) stimulation specifically in the dorsomedial striatum (DMS) of mice but not in the other substriatal regions, the dorsolateral striatum (DLS), and the nucleus accumbens (NAc). Once activated Fyn phosphorylates its substrate GluN2B, and we show that GluN2B is phosphorylated only in the DMS but not in the other striatal regions...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28910325/src-and-fyn-dependent-apical-membrane-trafficking-events-control-endothelial-lumen-formation-during-vascular-tube-morphogenesis
#17
Dae Joong Kim, Pieter R Norden, Jocelynda Salvador, David M Barry, Stephanie L K Bowers, Ondine Cleaver, George E Davis
Here we examine the question of how endothelial cells (ECs) develop their apical membrane surface domain during lumen and tube formation. We demonstrate marked apical membrane targeting of activated Src kinases to this apical domain during early and late stages of this process. Immunostaining for phosphotyrosine or phospho-Src reveals apical membrane staining in intracellular vacuoles initially. This is then followed by vacuole to vacuole fusion events to generate an apical luminal membrane, which is similarly decorated with activated phospho-Src kinases...
2017: PloS One
https://www.readbyqxmd.com/read/28888102/a-new-mechanism-of-resistance-to-abl1-tyrosine-kinase-inhibitors-in-a-bcr-abl1-positive-cell-line
#18
Kelly Airiau, Béatrice Turcq, François-Xavier Mahon, Francis Belloc
Tyrosine kinase inhibitors (TKI) constitute the frontline treatment for chronic myeloid leukemia patients. Dasatinib, a second-generation TKI, was developed to overcome TKI resistances. However, dasatinib resistances are also described but remain less characterized. To mimic in vivo acquired dasatinib resistance, the BCR-ABL1-positive cell line K562 was transiently treated with a pharmacological concentration of dasatinib, for a short time in the presence of stem cell factor. A dasatinib resistant counterpart (K562 RES) was developed...
August 31, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28887403/the-functions-of-reelin-in-membrane-trafficking-and-cytoskeletal-dynamics-implications-for-neuronal-migration-polarization-and-differentiation
#19
REVIEW
Jessica Santana, María-Paz Marzolo
Reelin is a large extracellular matrix protein with relevant roles in mammalian central nervous system including neurogenesis, neuronal polarization and migration during development; and synaptic plasticity with its implications in learning and memory, in the adult. Dysfunctions in reelin signaling are associated with brain lamination defects such as lissencephaly, but also with neuropsychiatric diseases like autism, schizophrenia and depression as well with neurodegeneration. Reelin signaling involves a core pathway that activates upon reelin binding to its receptors, particularly ApoER2 (apolipoprotein E receptor 2)/LRP8 (low-density lipoprotein receptor-related protein 8) and very low-density lipoprotein receptor, followed by Src/Fyn-mediated phosphorylation of the adaptor protein Dab1 (Disabled-1)...
September 7, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28864542/somatodendritic-accumulation-of-tau-in-alzheimer-s-disease-is-promoted-by-fyn-mediated-local-protein-translation
#20
Chuanzhou Li, Jürgen Götz
The cause of protein accumulation in neurodegenerative disease is incompletely understood. In Alzheimer's disease (AD), the axonally enriched protein Tau forms hyperphosphorylated aggregates in the somatodendritic domain. Consequently, a process of subcellular relocalization driven by Tau phosphorylation and detachment from microtubules has been proposed. Here, we reveal an alternative mechanism of de novo protein synthesis of Tau and its hyperphosphorylation in the somatodendritic domain, induced by oligomeric amyloid-β (Aβ) and mediated by the kinase Fyn that activates the ERK/S6 signaling pathway...
September 1, 2017: EMBO Journal
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