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https://www.readbyqxmd.com/read/27913425/cd36-mediates-h2o2-induced-calcium-influx-in-lung-microvascular-endothelial-cells
#1
Karthik Suresh, Laura Servinsky, Jose Reyes, Clark Undem, Joel Zaldumbide, Otgonchimeg Rentsendorj, Sruti Modekurty, Jeffrey M Dodd-O, Alan L Scott, David B Pearse, Larissa A Shimoda
Elevated levels of reactive oxygen species (ROS) and intracellular Ca2+ play a key role in endothelial barrier dysfunction in acute lung injury (ALI). We previously showed that H2O2-induced increases in intracellular calcium concentrations ([Ca2+]i) in LMVECs involve the membrane Ca2+ channel, transient receptor potential vanilloid-4 (TRPV4), and that inhibiting this channel attenuated H2O2-induced barrier disruption in vitro. We also showed that phosphorylation of TRPV4 by the Src family kinase, Fyn, contributes to H2O2-induced Ca2+ influx in LMVEC...
December 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27906494/alcohol-dependent-molecular-adaptations-of-the-nmda-receptor-system
#2
REVIEW
Nadege Morisot, Dorit Ron
Phenotypes such as motivation to consume alcohol, goal-directed alcohol seeking and habit formation contribute to the mechanisms underlying heavy alcohol use. Learning and memory processes greatly contribute to the establishment and maintenance of these behavioral phenotypes. The N-Methyl-D-Aspartate receptor (NMDAR) is a driving force of synaptic plasticity, a key cellular hallmark of learning and memory. Here, we describe data in rodents and humans linking signaling molecules that center around the NMDARs and behaviors associated with the development and/or maintenance of alcohol abuse...
December 1, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27898263/genetic-alterations-affecting-gtpases-and-t-cell-receptor-signaling-in-peripheral-t-cell-lymphomas
#3
Rebecca L Boddicker, Gina L Razidlo, Andrew L Feldman
Peripheral T-cell lymphomas (PTCLs) are rare, heterogeneous tumors with poor response to standard therapy and few targeted treatments available. The identification of mutations in the T-cell receptor (TCR) signaling pathway that either directly or indirectly affect Ras- and Rho-family GTPases is an emerging theme across PTCL subtypes. This review summarizes the role of GTPases in TCR signaling and highlights the constellation of mutations in this pathway among PTCLs. In particular, focus is given to the functional impact of the mutations and opportunities for targeted therapy...
November 29, 2016: Small GTPases
https://www.readbyqxmd.com/read/27876060/20-year-follow-up-study-of-danish-hht-patients-survival-and-causes-of-death
#4
Anette Kjeldsen, Katrine Saldern Aagaard, Pernille Mathiesen Tørring, Sören Möller, Anders Green
BACKGROUND: Hereditary Haemorrhagic Telangiectasia (HHT) is a dominantly inheritable disorder, with a wide variety of clinical manifestations due to presence of multiple arteriovenous manifestations. The most common mutations are found in HHT1 (ENG) and HHT2 (ACVRL1) patients, causing alterations in the TGF-β pathway which is responsible for angiogenesis. Modulations of angiogenesis may influence cancer rates. The objective of the study was to evaluate 20-year survival according to HHT subtype, as well as to evaluate differences in causes of death comparing HHT patients and controls...
November 22, 2016: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/27872592/a-pyrazolo-3-4-d-pyrimidine-compound-reduces-cell-viability-and-induces-apoptosis-in-different-hematological-malignancies
#5
Ilaria Laurenzana, Antonella Caivano, Francesco La Rocca, Stefania Trino, Luciana De Luca, Francesca D'Alessio, Silvia Schenone, Geppino Falco, Maurizio Botta, Luigi Del Vecchio, Pellegrino Musto
Molecular targeted therapies are based upon drugs acting on tumors by interfering with specific targets involved in growth and spread of cancer. Many targeted therapies were approved by Food and Drug Administration as standard treatment, others were introduced into preclinical or clinical studies on hematological malignancies (HMs). The development of drug-resistance in some HMs and the lack of effective treatments in other ones emphasized the need for searching new molecular targets and therapeutic agents...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27859601/the-protein-tyrosine-phosphatase-dep-1-promotes-migration-and-phagocytic-activity-of-microglial-cells-in-part-through-negative-regulation-of-fyn-tyrosine-kinase
#6
Nadine Schneble, Julia Müller, Stefanie Kliche, Reinhard Bauer, Reinhard Wetzker, Frank-D Böhmer, Zhao-Qi Wang, Jörg P Müller
Microglia cells are brain macrophages whose proper functioning is essential for maintenance and repair processes of the central nervous system (CNS). Migration and phagocytosis are critical aspects of microglial activity. By using genetically modified cell lines and knockout mice we demonstrate here that the receptor protein-tyrosine phosphatase (PTP) DEP-1 (also known as PTPRJ or CD148) acts as a positive regulator of both processes in vitro and in vivo. Notably, reduced microglial migration was detectable in brains of Ptprj(-/-) mice using a wounding assay...
November 17, 2016: Glia
https://www.readbyqxmd.com/read/27857754/protective-effect-of-tetrahydroxy-stilbene-glucoside-on-learning-and-memory-by-regulating-synaptic-plasticity
#7
Hong-Bo Luo, Yun Li, Zun-Jing Liu, Li Cao, Zhi-Qiang Zhang, Yong Wang, Xiao-Yan Zhang, Zhao Liu, Xiang-Qun Shi
Damage to synaptic plasticity induced by neurotoxicity of amyloid-beta is regarded to be one of the pathological mechanisms of learning and memory disabilities in Alzheimer's disease patients. This study assumed that the damage of amyloid-beta to learning and memory abilities was strongly associated with the changes in the Fyn/N-methyl-D-aspartate receptor 2B (NR2B) expression. An APP695V7171 transgenic mouse model of Alzheimer's disease was used and treatment with tetrahydroxy-stilbene glucoside was administered intragastrically...
September 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27837109/characterization-of-the-syk-dependent-t-cell-signaling-response-to-an-altered-peptide
#8
Jeoung-Eun Park, Jeffrey A Rotondo, David L Cullins, David D Brand, Ae-Kyung Yi, John M Stuart, Andrew H Kang, Linda K Myers
Rheumatoid arthritis is an autoimmune disorder characterized by T cell dysregulation. We have shown that an altered peptide ligand (A9) activates T cells to use an alternate signaling pathway that is dependent on FcRγ and spleen tyrosine kinase, resulting in downregulation of inflammation. In the experiments described in this study, we have attempted to determine the molecular basis of this paradox. Three major Src family kinases found in T cells (Lck, Fyn, and Lyn) were tested for activation following stimulation by A9/I-A(q) Unexpectedly we found they are not required for T cell functions induced by A9/I-A(q), nor are they required for APL stimulation of cytokines...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27784625/nicotine-induced-neuroplasticity-counteracts-the-effect-of-schizophrenia-linked-neuregulin-1-signaling-on-nmdar-function-in-the-rat-hippocampus
#9
Yoshihiko Yamazaki, Katumi Sumikawa
A high rate of heavy tobacco smoking among people with schizophrenia has been suggested to reflect self-medication and amelioration of cognitive dysfunction, a core feature of schizophrenia. NMDAR hypofunction is hypothesized to be a mechanism of cognitive dysfunction, and excessive schizophrenia-linked neuregulin 1 (NRG1) signaling through its receptor ErbB4 can suppress NMDAR function by preventing Src-mediated enhancement of NMDAR responses. Here we investigated whether chronic nicotine exposure in rats by subcutaneous injection of nicotine (0...
October 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27752082/inhibition-of-step61-ameliorates-deficits-in-mouse-and-hipsc-based-schizophrenia-models
#10
J Xu, B J Hartley, P Kurup, A Phillips, A Topol, M Xu, C Ononenyi, E Foscue, S-M Ho, T D Baguley, N Carty, C S Barros, U Müller, S Gupta, P Gochman, J Rapoport, J A Ellman, C Pittenger, B Aronow, A C Nairn, M W Nestor, P J Lombroso, K J Brennand
The brain-specific tyrosine phosphatase, STEP (STriatal-Enriched protein tyrosine Phosphatase) is an important regulator of synaptic function. STEP normally opposes synaptic strengthening by increasing N-methyl D-aspartate glutamate receptor (NMDAR) internalization through dephosphorylation of GluN2B and inactivation of the kinases extracellular signal-regulated kinase 1/2 and Fyn. Here we show that STEP61 is elevated in the cortex in the Nrg1(+/-) knockout mouse model of schizophrenia (SZ). Genetic reduction or pharmacological inhibition of STEP prevents the loss of NMDARs from synaptic membranes and reverses behavioral deficits in Nrg1(+/-) mice...
October 18, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27733622/the-residue-at-position-5-of-the-n-terminal-region-of-src-and-fyn-modulates-their-myristoylation-palmitoylation-and-membrane-interactions
#11
Efrat Gottlieb-Abraham, Orit Gutman, Govind M Pai, Ignacio Rubio, Yoav I Henis
The interactions of Src family kinases (SFKs) with the plasma membrane are crucial for their activity. They depend on their fatty-acylated N-termini, containing N-myristate and either a polybasic cluster (in Src) or palmitoylation sites (e.g., Fyn). To investigate the roles of these moieties in SFK membrane association, we used fluorescence recovery after photobleaching beam-size analysis to study the membrane interactions of c-Src-GFP (green fluorescent protein) or Fyn-GFP fatty-acylation mutants. Our studies showed for the first time that the membrane association of Fyn is more stable than that of Src, an effect lost in a Fyn mutant lacking the palmitoylation sites...
December 1, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27699828/high-content-screening-identifies-src-family-kinases-as-potential-regulators-of-ar-v7-expression-and-androgen-independent-cell-growth
#12
Adam T Szafran, Cliff Stephan, Michael Bolt, Maureen G Mancini, Marco Marcelli, Michael A Mancini
BACKGROUND: AR-V7 is an androgen receptor (AR) splice variant that lacks the ligand-binding domain and is isolated from prostate cancer cell lines. Increased expression of AR-V7 is associated with the transition from hormone-sensitive prostate cancer to more advanced castration-resistant prostate cancer (CRPC). Due to the loss of the ligand-binding domain, AR-V7 is not responsive to traditional AR-targeted therapies, and the mechanisms that regulate AR-V7 are still incompletely understood...
October 4, 2016: Prostate
https://www.readbyqxmd.com/read/27698077/src-family-kinases-are-regulated-in-multiple-myeloma-cells-by-phosphatase-of-regenerating-liver-3
#13
Pegah Abdollahi, Esten Nymoen Vandsemb, Magnus Aassved Hjort, Kristine Misund, Toril Holien, Anne-Marit Sponaas, Torstein B Ro, Tobias S Slordahl, Magne Borset
: Phosphatase of regenerating liver-3 (PTP4A3/PRL-3) is a dual specificity phosphatase that is up-regulated in various types of cancers and is related to poor prognosis and aggressive tumor behavior. The expression level of PRL-3 is elevated in response to several anti-apoptotic cytokines, including interleukin-6 (IL6), in cancer cells from patients with multiple myeloma (MM) and can promote survival and migration. Here it is demonstrated that PRL-3 activates Src kinase in the IL6-dependent MM cell line INA-6...
October 3, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27697866/shp-1-acts-as-a-key-regulator-of-alloresponses-by-modulating-lfa-1-mediated-adhesion-in-primary-murine-t-cells
#14
Martin G Sauer, Jessica Herbst, Ulf Diekmann, Christopher E Rudd, Christian Kardinal
The clinical potential of transplantation is often reduced by T cell-mediated alloresponses that cause graft rejection or graft-versus-host disease. Integrin-mediated adhesion between alloreactive T cells and antigen-presenting cells is essential for allorejection. The identity of the signaling events needed for the activation of integrins such as LFA-1 is poorly understood. Here, we identified a novel role of the protein tyrosine phosphatase SHP-1 in the regulation of murine LFA-1-mediated adhesion in an allograft setting...
December 15, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27694211/ligand-induced-growth-and-compaction-of-cd36-nanoclusters-enriched-in-fyn-induces-fyn-signaling
#15
John Maringa Githaka, Anthony R Vega, Michelle A Baird, Michael W Davidson, Khuloud Jaqaman, Nicolas Touret
Nanoclustering is an emerging organizational principle for membrane-associated proteins. The functional consequences of nanoclustering for receptor signaling remain largely unknown. Here, we applied quantitative multi-channel high- and super-resolution imaging to analyze the endothelial cell surface receptor CD36, the clustering of which upon binding to multivalent ligands, such as the anti-angiogenic factor thrombospondin-1 (TSP-1), is thought to be crucial for signaling. We found that a substantial fraction of unligated CD36 exists in nanoclusters, which not only promote TSP-1 binding but are also enriched with the downstream effector Fyn...
November 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27692963/dynamically-coupled-residues-within-the-sh2-domain-of-fyn-are-key-to-unlocking-its-activity
#16
Radu Huculeci, Elisa Cilia, Agatha Lyczek, Lieven Buts, Klaartje Houben, Markus A Seeliger, Nico van Nuland, Tom Lenaerts
Src kinase activity is controlled by various mechanisms involving a coordinated movement of kinase and regulatory domains. Notwithstanding the extensive knowledge related to the backbone dynamics, little is known about the more subtle side-chain dynamics within the regulatory domains and their role in the activation process. Here, we show through experimental methyl dynamic results and predicted changes in side-chain conformational couplings that the SH2 structure of Fyn contains a dynamic network capable of propagating binding information...
November 1, 2016: Structure
https://www.readbyqxmd.com/read/27665472/fyn-related-kinase-expression-predicts-favorable-prognosis-in-patients-with-cervical-cancer-and-suppresses-malignant-progression-by-regulating-migration-and-invasion
#17
Xiaofeng Zhang, Fengshuang Li, Prof Linzhong Zhu
AIM: To investigate expression pattern, clinical significance and potential roles of fyn related kinase (FRK) in cervical cancer. METHODS: Expression of FRK protein and mRNA in 100 pairs of cervical cancer and matched non-cancerous tissue samples were detected by Western blot, immunohistochemistry and quantitative PCR, respectively. Statistical analyses were performed to evaluate associations of FRK protein expression with various clinicopathologic features and patients' prognosis...
September 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27639648/cellular-prion-protein-as-a-receptor-for-amyloid-%C3%AE-oligomers-in-alzheimer-s-disease
#18
Santiago V Salazar, Stephen M Strittmatter
Soluble oligomers of amyloid-beta (Aβo) are implicated by biochemical and genetic evidence as a trigger for Alzheimer's disease (AD) pathophysiology. A key step is Aβo interaction with the neuronal surface to initiate a cascade of altered signal transduction leading to synaptic dysfunction and damage. This review discusses neuronal cell surface molecules with high affinity selectively for oligomeric disease-associated states of Aβ, with a particular focus on the role of cellular prion protein (PrP(C)) in this process...
September 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27626315/fyn-phosphorylates-ampk-to-inhibit-ampk-activity-and-amp-dependent-activation-of-autophagy
#19
Eijiro Yamada, Shuichi Okada, Claire C Bastie, Manu Vatish, Yasuyo Nakajima, Ryo Shibusawa, Atsushi Ozawa, Jeffrey E Pessin, Masanobu Yamada
We previously demonstrated that proto-oncogene Fyn decreased energy expenditure and increased metabolic phenotypes. Also Fyn decreased autophagy-mediated muscle mass by directly inhibiting LKB1 and stimulating STAT3 activities, respectively. AMPK, a downstream target of LKB1, was recently identified as a key molecule controlling autophagy. Here we identified that Fyn phosphorylates the α subunit of AMPK on Y436 and inhibits AMPK enzymatic activity without altering the assembly state of the AMPK heterotrimeric complex...
September 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27624844/inhibition-of-src-family-kinases-improves-cognitive-function-after-intraventricular-hemorrhage-or-intraventricular-thrombin
#20
Da Zhi Liu, Ben Waldau, Bradley P Ander, Xinhua Zhan, Boryana Stamova, Glen C Jickling, Bruce G Lyeth, Frank R Sharp
Intraventricular hemorrhage causes spatial memory loss, but the mechanism remains unknown. Our recent studies demonstrated that traumatic brain injury activates Src family kinases, which cause spatial memory loss. To test whether the spatial memory loss was due to blood in the ventricles, which activated Src family kinases, we infused autologous whole blood or thrombin into the lateral ventricles of adult rats to model non-traumatic intraventricular hemorrhage. Hippocampal neuron loss was examined 1 day to 5 weeks later...
September 13, 2016: Journal of Cerebral Blood Flow and Metabolism
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