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https://www.readbyqxmd.com/read/28526038/phosphorylation-of-tau-at-y18-but-not-tau-fyn-binding-is-required-for-tau-to-modulate-nmda-receptor-dependent-excitotoxicity-in-primary-neuronal-culture
#1
Takashi Miyamoto, Liana Stein, Reuben Thomas, Biljana Djukic, Praveen Taneja, Joseph Knox, Keith Vossel, Lennart Mucke
BACKGROUND: Hyperexcitability of neuronal networks can lead to excessive release of the excitatory neurotransmitter glutamate, which in turn can cause neuronal damage by overactivating NMDA-type glutamate receptors and related signaling pathways. This process (excitotoxicity) has been implicated in the pathogenesis of many neurological conditions, ranging from childhood epilepsies to stroke and neurodegenerative disorders such as Alzheimer's disease (AD). Reducing neuronal levels of the microtubule-associated protein tau counteracts network hyperexcitability of diverse causes, but whether this strategy can also diminish downstream excitotoxicity is less clear...
May 19, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28498896/inhibition-of-prdm14-expression-in-pancreatic-cancer-suppresses-cancer-stem-like-properties-and-liver-metastasis-in-mice
#2
Chiharu Moriya, Hiroaki Taniguchi, Kanjiro Miyata, Nobuhiro Nishiyama, Kazunori Kataoka, Kohzoh Imai
Pancreatic cancer is one of the most lethal types of cancer, with aggressive properties characterized by metastasis, recurrence, and drug resistance. Cancer stem cells are considered to be responsible for these properties. PRDM14, a transcriptional regulator that maintains pluripotency in embryonic stem cells, is overexpressed in some cancers. Here, we assessed PRDM14 expression and the effects of PRDM14 knockdown on cancer stem-like phenotypes in pancreatic cancer. We observed that PRDM14 protein was overexpressed in pancreatic cancer tissues compared with normal pancreatic tissues...
May 12, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28497343/bdnf-contributes-to-spinal-long-term-potentiation-and-mechanical-hypersensitivity-via-fyn-mediated-phosphorylation-of-nmda-receptor-glun2b-subunit-at-tyrosine-1472-in-rats-following-spinal-nerve-ligation
#3
Song Li, Jie Cai, Zhi-Bo Feng, Zi-Run Jin, Bo-Heng Liu, Hong-Yan Zhao, Hong-Bo Jing, Tian-Jiao Wei, Guan-Nan Yang, Ling-Yu Liu, Yan-Jun Cui, Guo-Gang Xing
Previously we have demonstrated that brain-derived neurotrophic factor (BDNF) contributes to spinal long-term potentiation (LTP) and pain hypersensitivity through activation of GluN2B-containing N-methyl-D-aspartate (GluN2B-NMDA) receptors in rats following spinal nerve ligation (SNL). However, the molecular mechanisms by which BDNF impacts upon GluN2B-NMDA receptors and spinal LTP still remain unclear. In this study, we first documented that Fyn kinase-mediated phosphorylation of GluN2B subunit at tyrosine 1472 (pGluN2B(Y1472)) was involved in BDNF-induced spinal LTP and pain hypersensitivity in intact rats...
May 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28473753/mechanical-strain-promotes-oligodendrocyte-differentiation-by-global-changes-of-gene-expression
#4
Anna Jagielska, Alexis L Lowe, Ekta Makhija, Liliana Wroblewska, Jochen Guck, Robin J M Franklin, G V Shivashankar, Krystyn J Van Vliet
Differentiation of oligodendrocyte progenitor cells (OPC) to oligodendrocytes and subsequent axon myelination are critical steps in vertebrate central nervous system (CNS) development and regeneration. Growing evidence supports the significance of mechanical factors in oligodendrocyte biology. Here, we explore the effect of mechanical strains within physiological range on OPC proliferation and differentiation, and strain-associated changes in chromatin structure, epigenetics, and gene expression. Sustained tensile strain of 10-15% inhibited OPC proliferation and promoted differentiation into oligodendrocytes...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28456200/microscopic-insight-into-thermodynamics-of-conformational-changes-of-sap-slam-complex-in-signal-transduction-cascade
#5
Sudipta Samanta, Sanchita Mukherjee
The signalling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, associate with SLAM-associated protein (SAP)-related molecules, composed of single SH2 domain architecture. SAP activates Src-family kinase Fyn after SLAM ligation, resulting in a SLAM-SAP-Fyn complex, where, SAP binds the Fyn SH3 domain that does not involve canonical SH3 or SH2 interactions. This demands insight into this SAP mediated signalling cascade. Thermodynamics of the conformational changes are extracted from the histograms of dihedral angles obtained from the all-atom molecular dynamics simulations of this structurally well characterized SAP-SLAM complex...
April 28, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28448896/differentially-methylated-embryonal-fyn-associated-substrate-efs-gene-as-a-blood-specific-epigenetic-marker-and-its-potential-application-in-forensic-casework
#6
Athina Vidaki, Cecilia Johansson, Federica Giangasparo
DNA methylation patterns have the ability to reveal the activities of genes within a certain tissue at a particular time point. Tissue-specific DNA methylation patterns have been previously investigated for their applicability in the identification of forensically relevant body fluids, however there is still a lack in robust markers. While following a genome-wide scale investigation has a great potential to reveal useful tissue-specific changes, a gene-targeted approach can also lead to significant outcomes, especially in genomic locations not included in the genome-wide experiments...
April 19, 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/28445842/%C3%AE-eta-eudesmol-reduces-stem-cell-factor-induced-mast-cell-migration
#7
Sun-Young Nam, Hee-Yun Kim, Hyung-Min Kim, Hyun-Ja Jeong
Previously, we showed the inhibitory effects of β-eudesmol on mast cell-mediated allergic inflammatory responses. Stem cell factor (SCF) participates in allergic reactions through the differentiation and migration of mast cells. However, the effects of β-eudesmol on SCF-mediated allergic reactions are poorly understood. Herein, we showed that a treatment of rat peritoneal mast cells (RPMCs) with β-eudesmol markedly suppressed SCF-induced mast cell migration and morphological alterations in a concentration-dependent manner...
April 23, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28442050/lonidamine-ethyl-ester-mediated-remodelling-of-the-sertoli-cell-cytoskeleton-induces-phosphorylation-of-plakoglobin-and-promotes-its-interaction-with-%C3%AE-catenin-at-the-blood-testis-barrier
#8
Dolores D Mruk, Michele Bonanomi, Bruno Silvestrini
Several compounds affect male fertility by disrupting the adhesion of germ cells to Sertoli cells, which results in the release of undeveloped germ cells into the seminiferous tubule lumen that are incapable of fertilising the ovum. Indazole carboxylic acids are one class of compounds exhibiting such effects and they have been investigated as non-hormonal contraceptives for potential human use. The aims of this study were to investigate the effects of lonidamine-ethyl ester, an indazole carboxylic acid, on spermatogenesis and cell junctions, in particular, desmosomes...
April 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28440917/atf3-inhibits-the-inflammation-induced-by-mycoplasma-pneumonia-in-vitro-and-in-vivo
#9
Jing Wang, Wei Cheng, Zhen Wang, Lihong Xin, Wen Zhang
OBJECTIVES: Activating transcription factor-3 (ATF3) is a key regulator of inflammatory responses. We aimed to investigate the effects and mechanisms of ATF3 on the inflammatory cytokines are induced by Mycoplasma pneumonia (MP). STUDY DESIGN: RAW264.7 and mouse peritoneal macrophages were exposed to various time with or without MP infection (3, 6, 12, 24, and 48 h), and detect the expression of ATF3. Adenovirus-expression of ATF3 (Ad/ATF3) or Ad/βgal was transfected into cells which were exposed to MP for 48 h, RT-PCR and ELISA was used to evaluate the expression and secretion of TNF-α, IL-1β, IL-6, and IL-18...
April 25, 2017: Pediatric Pulmonology
https://www.readbyqxmd.com/read/28432466/calpain-inhibition-prevents-flotillin-re-ordering-and-src-family-activation-during-capacitation
#10
Deneb Maldonado-García, Monica L Salgado-Lucio, Ana L Roa-Espitia, Tania Reyes-Miguel, Enrique O Hernández-González
Prior to fertilization, mammalian sperm undergo several molecular, biochemical and physiological changes in a process termed capacitation. However, the mechanisms explaining the involvement of cytoskeletal remodeling and membrane re-ordering in each process prior to fertilization remain poorly understood. We found that the migration of both flotillin microdomains and Src family kinases towards the apical ridge of guinea pig sperm occurs under capacitating conditions. This re-ordering is associated with spectrin cleavage by calpain...
April 22, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28424976/the-involvement-of-nr2b-and-tau-protein-in-mg132-induced-creb-dephosphorylation
#11
Min Xie, Yuan Li, Shao-Hui Wang, Qun-Tao Yu, Xin Meng, Xiao-Mei Liao
Transcription factor cAMP response element-binding protein (CREB) plays a critical role in memory formation. Ubiquitin-proteasome system-dependent protein degradation affects the upstream signaling pathways which regulate CREB activity. However, the molecular mechanisms of proteasome inhibition on reductive CREB activity are still unclear. The current study demonstrated that MG132-inhibited proteasome activity resulted in a dose dependence of CREB dephosphorylation at Ser133 as well as decreased phosphorylation of N-methyl-D-aspartate (NMDA) receptor subunit NR2B (Tyr1472) and its tyrosine protein kinase Fyn (Tyr416)...
April 19, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28420443/tau-phosphorylation-induced-by-severe-closed-head-traumatic-brain-injury-is-linked-to-the-cellular-prion-protein
#12
Richard Rubenstein, Binggong Chang, Natalia Grinkina, Eleanor Drummond, Peter Davies, Meir Ruditzky, Deep Sharma, Kevin Wang, Thomas Wisniewski
Studies in vivo and in vitro have suggested that the mechanism underlying Alzheimer's disease (AD) neuropathogenesis is initiated by an interaction between the cellular prion protein (PrP(C)) and amyloid-β oligomers (Aβo). This PrP(C)-Aβo complex activates Fyn kinase which, in turn, hyperphosphorylates tau (P-Tau) resulting in synaptic dysfunction, neuronal loss and cognitive deficits. AD transgenic mice lacking PrP(C) accumulate Aβ, but show normal survival and no loss of spatial learning and memory suggesting that PrP(C) functions downstream of Aβo production but upstream of intracellular toxicity within neurons...
April 18, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28393199/smad4-deletion-in-blood-vessel-endothelial-cells-promotes-ovarian-cancer-metastasis
#13
Jie Yang, Ya Wang, Zhen Zeng, Long Qiao, Liang Zhuang, Qinglei Gao, Ding Ma, Xiaoyuan Huang
SMAD4 is a critical co-smad in signal transduction pathways activated in response to transforming growth factor-β (TGF-β)-related ligands, regulating cell growth and differentiation. The roles played by SMAD4 inactivation in tumors highlighted it as a tumor-suppressor gene. Herein, we report that loss of SMAD4 expression in vascular endothelial cells promotes ovarian cancer invasion. SiRNA transfer of this gene in the HUVEC reduced SMAD4 protein expression and function. Although it reduced the vessel endothelial cell tubule formation in vitro and in vivo, it did not affect the tumor growth significantly in vivo...
May 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28389375/striatal-enriched-phosphatase-61-inhibited-the-nociceptive-plasticity-in-spinal-cord-dorsal-horn-of-rats
#14
Zhan-Wei Suo, Jiang-Ping Liu, Man Xue, Yun-Hui Yang, Xian Yang, Jun Xie, Xiao-Dong Hu
Striatal-enriched phosphatase 61 (STEP61) is a member of intracellular protein tyrosine phosphatases, which is involved in the regulation of synaptic plasticity and a line of neuropsychiatric disorders. This protein tyrosine phosphatase is also abundant in pain-related spinal cord dorsal horn neurons. However, whether and how this tyrosine phosphatase modulates the nociceptive plasticity and behavioral hypersensitivity remain largely unknown. The present study recorded the long-term potentiation (LTP) of primary afferent C fiber-evoked field potentials in vivo in superficial dorsal horn of rats, and tested the possible role of STEP61 in spinal LTP...
June 3, 2017: Neuroscience
https://www.readbyqxmd.com/read/28383553/oxidation-of-kcnb1-potassium-channels-triggers-apoptotic-integrin-signaling-in-the-brain
#15
Wei Yu, Manasa Gowda, Yashsavi Sharad, Surindo A Singh, Federico Sesti
Oxidative modification of the voltage-gated potassium (K(+)) channel KCNB1 promotes apoptosis in the neurons of cortex and hippocampus through a signaling pathway mediated by Src tyrosine kinases. How oxidation of the channel is transduced into Src recruitment and activation, however, was not known. Here we show that the apoptotic signal originates from integrins, which form macromolecular complexes with KCNB1 channels. The initial stimulus is transduced to Fyn and possibly other Src family members by focal adhesion kinase (FAK)...
April 6, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28380689/docking-and-molecular-dynamics-simulations-of-the-fyn-sh3-domain-with-free-and-phospholipid-bilayer-associated-18-5-kda-myelin-basic-protein-mbp-insights-into-a-non-canonical-and-fuzzy-interaction
#16
Kyrylo Bessonov, Kenrick A Vassall, George Harauz
The molecular details of the association between the human Fyn-SH3 domain, and the fragment of 18.5-kDa myelin basic protein (MBP) spanning residues S38-S107 (denoted as xα2-peptide, murine sequence numbering), were studied in silico via docking and molecular dynamics over 50-ns trajectories. The results show that interaction between the two proteins is energetically favorable and heavily-dependent on the MBP proline-rich region (P93-P98) in both aqueous and membrane environments. In aqueous conditions, the xα2-peptide/Fyn-SH3 complex adopts a "sandwich"-like structure...
April 5, 2017: Proteins
https://www.readbyqxmd.com/read/28368000/src-family-kinases-fyn-and-lyn-are-constitutively-activated-and-mediate-plasmacytoid-dendritic-cell-responses
#17
S Dallari, M Macal, M E Loureiro, Y Jo, L Swanson, C Hesser, P Ghosh, E I Zuniga
Plasmacytoid dendritic cells (pDC) are type I interferon-producing cells with critical functions in a number of human illnesses; however, their molecular regulation is incompletely understood. Here we show the role of Src family kinases (SFK) in mouse and human pDCs. pDCs express Fyn and Lyn and their activating residues are phosphorylated both before and after Toll-like receptor (TLR) stimulation. Fyn or Lyn genetic ablation as well as treatment with SFK inhibitors ablate pDC (but not conventional DC) responses both in vitro and in vivo...
April 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28363782/fyn-regulates-multipolar-bipolar-transition-and-neurite-morphogenesis-of-migrating-neurons-in-the-developing-neocortex
#18
Yingxue Huang, Guohong Li, Lei An, Yanle Fan, Xinran Cheng, Xuzhao Li, Yupeng Yin, Rihua Cong, Shulin Chen, Shanting Zhao
Fyn is a non-receptor protein tyrosine kinase that belongs to Src family kinases. Fyn plays a critical role in neuronal migration, but the mechanism remains unclear. Here, we reported that suppression of Fyn expression in mouse cerebral cortex led to migration defects of both early-born and late-born neurons. Morphological analysis showed that loss of Fyn function impaired multipolar-bipolar transition of newly generated neurons and neurite formation in the early phase of migration. Moreover, Fyn inhibition increased the length of leading process and decreased the branching number of the migrating cortical neurons...
June 3, 2017: Neuroscience
https://www.readbyqxmd.com/read/28360834/an-aberrant-phosphorylation-of-amyloid-precursor-protein-tyrosine-regulates-its-trafficking-and-the-binding-to-the-clathrin-endocytic-complex-in-neural-stem-cells-of-alzheimer-s-disease-patients
#19
Ebbe T Poulsen, Filomena Iannuzzi, Helle F Rasmussen, Thorsten J Maier, Jan J Enghild, Arne L Jørgensen, Carmela Matrone
Alzheimer's disease (AD) is the most common cause of dementia and is likely caused by defective amyloid precursor protein (APP) trafficking and processing in neurons leading to amyloid plaques containing the amyloid-β (Aβ) APP peptide byproducts. Understanding how APP is targeted to selected destinations inside neurons and identifying the mechanisms responsible for the generation of Aβ are thus the keys for the advancement of new therapies. We previously developed a mouse model with a mutation at tyrosine (Tyr) 682 in the C-terminus of APP...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28347651/selective-targeting-of-sh2-domain-phosphotyrosine-interactions-of-src-family-tyrosine-kinases-with-monobodies
#20
Tim Kükenshöner, Nadine Eliane Schmit, Emilie Bouda, Fern Sha, Florence Pojer, Akiko Koide, Markus Seeliger, Shohei Koide, Oliver Hantschel
The binding of Src-homology 2 (SH2) domains to phosphotyrosine (pY) sites is critical for the autoinhibition and substrate recognition of the eight Src family kinases (SFKs). The high sequence conservation of the 120 human SH2 domains poses a significant challenge to selectively perturb the interactions of even the SFK SH2 family against the rest of the SH2 domains. We have developed synthetic binding proteins, termed monobodies, for six of the SFK SH2 domains with nanomolar affinity. Most of these monobodies competed with pY ligand binding and showed strong selectivity for either the SrcA (Yes, Src, Fyn, Fgr) or SrcB subgroup (Lck, Lyn, Blk, Hck)...
May 5, 2017: Journal of Molecular Biology
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