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https://www.readbyqxmd.com/read/28736554/differential-requirements-for-src-family-kinases-in-syk-or-zap70-mediated-slp-76-phosphorylation-in-lymphocytes
#1
Frank Fasbender, Maren Claus, Sabine Wingert, Mina Sandusky, Carsten Watzl
In a synthetic biology approach using Schneider (S2) cells, we show that SLP-76 is directly phosphorylated at tyrosines Y113 and Y128 by SYK in the presence of ITAM-containing adapters such as CD3ζ, DAP12, or FcεRγ. This phosphorylation was dependent on at least one functional ITAM and a functional SH2 domain within SYK. Inhibition of Src-kinases by inhibitors PP1 and PP2 did not reduce SLP-76 phosphorylation in S2 cells, suggesting an ITAM and SYK dependent, but Src-kinase independent signaling pathway...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28729437/estradiol-induced-regulation-of-glut4-in-3t3-l1-cells-involvement-of-esr1-and-akt-activation
#2
Raquel Campello, Luciana Fátima, João Barreto-Andrade, Thais Fg Lucas, Rosana Cristina Tieko Mori, Catarina Segreti Porto, Ubiratan Fabres Machado
Impaired insulin-stimulated glucose uptake involves reduced expression of the GLUT4 (solute carrier family 2 facilitated glucose transporter member 4, SLC2A4 gene). 17β-estradiol (E2) modulates SLC2A4/GLUT4 expression, but the involved mechanisms are unclear. Although E2 exerts its biological effects by binding to estrogen receptors 1/2 (ESR1/2), which are nuclear transcriptional factors; extranuclear effects have also been proposed. We hypothesize that E2 regulates GLUT4 through a mechanism related to extranuclear ESR1...
July 20, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28673614/ros-dependent-activation-of-rhoa-rho-kinase-in-pulmonary-artery-role-of-src-family-kinases-and-arhgef1
#3
Charles E MacKay, Yasin Shaifta, Vladimir V Snetkov, Asvi A Francois, Jeremy P T Ward, Greg A Knock
The role of reactive oxygen species (ROS) in smooth muscle contraction is poorly understood. We hypothesised that G-protein coupled receptor (GPCR) activation and hypoxia induce Rho-kinase activity and contraction in rat intra-pulmonary artery (IPA) via stimulation of ROS production and subsequent Src-family kinase (SrcFK) activation. The T-type prostanoid receptor agonist U46619 induced ROS production in pulmonary artery smooth muscle cells (PASMC). U46619 also induced c-Src cysteine oxidation, SrcFK auto-phosphorylation, MYPT-1 and MLC20 phosphorylation and contraction in IPA, and all these responses were inhibited by antioxidants (ebselen, Tempol)...
July 1, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28670375/lyn-kinase-enhanced-hepatic-fibrosis-by-modulating-the-activation-of-hepatic-stellate-cells
#4
Yin Li, Lin Xiong, Jianping Gong
The non-selectivity of tyrosine kinase inhibitors is the leading cause of drug withdrawals, and limits their application in anti-fibrosis. The role of Src tyrosine kinase Lyn in hepatic fibrosis remains elusive. In this study, we aimed to elucidate the role of Lyn kinase in the pathogenesis of hepatic fibrosis. Through examining Lyn-transgenic (Lyn TG) mice treated with CCl4 (carbon tetrachloride), we determined whether Lyn kinase is involved in the pathogenesis of hepatic fibrosis. On top of that, we also investigated the role of Lyn in the activation of hepatic stellate cells (HSCs) in vitro...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28658050/effects-of-src-kinase-inhibition-on-expression-of-pro-caspase-2-after-brain-hypoxia-in-a-piglet-animal-model
#5
Dimitrios Angelis, Maria Delivoria-Papadopoulos
Caspase-2 has features of both initiator and effector caspases. Previously, we have shown that brain hypoxia-induced production of caspases 1, 3, 8, and 9 is Src kinase mediated, a nonreceptor intracellular family of kinases. The present study tests the hypothesis that hypoxia results in increased expression of caspase-2 and this effect is mediated by Src kinase. Two to three days old newborn piglets were subjected to normoxia, hypoxia (Hx, FiO2 7%), and Src kinase inhibition (using PP2, 1 mg/kg, intravenous), followed by 30 min of acute hypoxia (Hx+PP2)...
August 16, 2017: Neuroreport
https://www.readbyqxmd.com/read/28626342/effects-of-src-kinase-inhibition-on-expression-of-protein-tyrosine-phosphatase-1b-after-brain-hypoxia-in-a-piglet-animal-model
#6
Dimitrios Angelis, Maria Delivoria-Papadopoulos
BACKGROUND: Protein tyrosine phosphatases (PTPs) in conjunction with protein tyrosine kinases (PTKs) regulate cellular processes by posttranslational modifications of signal transduction proteins. PTP nonreceptor type 1B (PTP-1B) is an enzyme of the PTP family. We have previously shown that hypoxia induces an increase in activation of a class of nonreceptor PTK, the Src kinases. In the present study, we investigated the changes that occur in the expression of PTP-1B in the cytosolic component of the brain of newborn piglets acutely after hypoxia as well as long term for up to 2 weeks...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28597397/protein-kinase-c%C3%AE-gene-depletion-protects-against-methamphetamine-induced-impairments-in-recognition-memory-and-erk1-2-signaling-via-upregulation-of-glutathione-peroxidase-1-gene
#7
The-Vinh Tran, Eun-Joo Shin, Lan Thuy Ty Nguyen, Youngho Lee, Dae-Joong Kim, Ji Hoon Jeong, Choon-Gon Jang, Seung-Yeol Nah, Kazuya Toriumi, Toshitaka Nabeshima, Kiyofumi Yamada, Hyoung-Chun Kim
Accumulating evidence has suggested that repeated treatment with methamphetamine (MA) resulted in cognitive impairments. Importantly, we show that selective upregulation of protein kinase Cδ (PKCδ) in the prefrontal cortex (PFC) of wild-type mice persisted for 28 days post withdrawal of MA. On day 28, the MA-induced increase in phospho-PKCδ expression and decrease in phospho-ERK1/2 expression were significantly attenuated by both the Src inhibitor PP2 and the dopamine D1 receptor antagonist SCH 23390. However, neither protein kinase A inhibitor H89 nor calmodulin-dependent protein kinase II inhibitor KN93 attenuated MA-induced alterations in phospho-PKCδ expression and phospho-ERK1/2 expression...
June 9, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28592949/development-of-multiplex-pcr-for-simultaneous-detection-of-citrus-viruses-and-the-incidence-of-citrus-viral-diseases-in-late-maturity-citrus-trees-in-jeju-island
#8
Jae Wook Hyun, Rok Yeon Hwang, Kyung Eun Jung
Satsuma dwarf virus (SDV) or Citrus mosaic sadwavirus (CiMV) were not consistently detected in RT-PCR assay with the primer sets based on gene of Japan isolates. SDV and CiMV isolates were distinctively divided into two groups based on phylogenetic analysis of PP2 gene cloned from 22 Korean isolates, and the Korean CiMV and SDV isolates shared 95.5-96.2% and 97.1-97.7% sequence identity with Japanese isolate, respectively. We developed PP2-1 primer set based on the PP2 gene sequence of Korean isolates to simultaneously and effectively detect SDV and CiMV...
June 2017: Plant Pathology Journal
https://www.readbyqxmd.com/read/28592413/recruitment-of-endosomal-signaling-mediates-the-forskolin-modulation-of-guinea-pig-cardiac-neuron-excitability
#9
Jean C Hardwick, Todd A Clason, John D Tompkins, Beatrice M Girard, Caitlin N Baran, Laura A Merriam, Victor May, Rodney L Parsons
Forskolin, a selective activator of adenylyl cyclase (AC), commonly is used to establish actions of G protein coupled receptors (GPCRs) that are initiated primarily through activation of AC/cAMP signaling pathways. In the present study, forskolin was used to evaluate the potential role of AC/cAMP, which is a major signaling mechanism for the pituitary adenylate cyclase-activating polypeptide (PACAP)-selective PAC1 receptor, in the regulation of guinea pig cardiac neuronal excitability. Forskolin (5-10 µM) increases excitability in ~60 % of the cardiac neurons...
June 7, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28585567/role-of-src-family-kinases-in-bdnf-mediated-suppression-of-cocaine-seeking-and-prevention-of-cocaine-induced-erk-glun2a-and-glun2b-dephosphorylation-in-the-prelimbic-cortex
#10
Sarah M Barry, Jacqueline F McGinty
Models of relapse have demonstrated that neuroadaptations in reward circuits following cocaine self-administration (SA) underlie reinstatement of drug-seeking. Dysregulation of the pathway from the prelimbic (PrL) cortex to the nucleus accumbens is implicated in reinstatement. A single BDNF infusion into the PrL cortex following a final cocaine SA session results in attenuation of reinstatement of cocaine-seeking. Inhibiting BDNF's receptor, TrkB, ERK/MAP kinase activation, or NMDA receptors blocks this attenuating effect, indicating that the interaction between glutamate-mediated synaptic activity and TrkB signaling is imperative to BDNF's suppressive effect on drug-seeking...
June 6, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28535499/the-role-of-5-htr6-in-mossy-fiber-sprouting-activating-fyn-and-p-erk1-2-in-pilocarpine-induced-chronic-epileptic-rats
#11
Wanhui Lin, Wenli Huang, Shenggen Chen, Mingxing Lin, Qingyu Huang, Huapin Huang
OBJECTIVE: Our primary objective is to verify whether 5-HTR6 is involved in the development of mossy fiber sprouting (MFS), and to determine how the progression of MFS is affected by 5-HTR6. METHODS: A total of 90 male adult Sprague-Dawley rats were allocated into either the control group (n=36) or the epileptic group (n=54). Status epilepticus (SE) of rats was induced by the intraperitoneal (i.p.) injection of LiCl-pilocarpine. We conducted our experiments in two stages...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28506997/the-phosphatase-pgam5-antagonizes-wnt-%C3%AE-catenin-signaling-in-embryonic-anterior-posterior-axis-patterning
#12
Verena Rauschenberger, Dominic B Bernkopf, Sabrina Krenn, Kowcee Jalal, Jens Heller, Jürgen Behrens, Marc Gentzel, Alexandra Schambony
The scaffold protein Dishevelled is a central intracellular component of Wnt signaling pathways. Various kinases have been described that regulate and modulate Wnt signaling through phosphorylation of Dishevelled. However, besides general protein phosphatases 1 and 2 (PP1 and PP2), no specific protein phosphatases have been identified. Here, we report on the identification and functional characterization of the protein phosphatase Pgam5 in vitro and in vivo in Xenopus Pgam5 is a novel antagonist of Wnt/β-Catenin signaling in human cells and Xenopus embryogenesis...
June 15, 2017: Development
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
#13
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/28478994/emerging-paradigms-of-g-protein-coupled-receptor-dephosphorylation
#14
REVIEW
Andrea Kliewer, Rainer K Reinscheid, Stefan Schulz
Elucidation of the molecular mechanisms underlying G protein-coupled receptor (GPCR) dephosphorylation remains a major challenge. While specific GPCR phosphatases (GRPs) have eluded identification, prevailing models propose that receptors must first internalize into acidic endosomes to become dephosphorylated in a housekeeping-like process. Recently, phosphosite-specific antibodies, combined with siRNAs targeting specific phosphatase transcripts, have facilitated the identification of distinct protein phosphatase 1 (PP1) and PP2 catalytic subunits as bona fide GRPs...
May 4, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28470937/endothelial-cell-derived-matrix-promotes-the-metabolic-functional-maturation-of-hepatocyte-via-integrin-src-signalling
#15
Xinyue Guo, Weihong Li, Minghui Ma, Xin Lu, Haiyan Zhang
The extracellular matrix (ECM) microenvironment is involved in the regulation of hepatocyte phenotype and function. Recently, the cell-derived extracellular matrix has been proposed to represent the bioactive and biocompatible materials of the native ECM. Here, we show that the endothelial cell-derived matrix (EC matrix) promotes the metabolic maturation of human adipose stem cell-derived hepatocyte-like cells (hASC-HLCs) through the activation of the transcription factor forkhead box protein A2 (FOXA2) and the nuclear receptors hepatocyte nuclear factor 4 alpha (HNF4α) and pregnane X receptor (PXR)...
May 4, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28454278/the-associated-pyrazolopyrimidines-pp1-and-pp2-inhibit-protein-tyrosine-kinase-6-activity-and-suppress-breast-cancer-cell-proliferation
#16
Hyun Jae Shim, Han Ie Kim, Seung-Taek Lee
Protein tyrosine kinase (PTK)6, also known as breast tumor kinase, is a non-receptor tyrosine kinase. It is closely associated with, but evolutionarily distinct from, the Src family members. PTK6 has a role in proliferation, migration and invasion in various cancers, and therefore has been suggested as a potentially valuable therapeutic target. In an attempt to develop PTK6 inhibitors, chemicals known to inhibit various kinases were screened for their ability to inhibit PTK6. Pyrazolopyrimidine (PP)1, PP2 and a lymphocyte-specific protein tyrosine kinase inhibitor strongly inhibited the catalytic activity of PTK6 in vitro...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454121/kr%C3%A3-ppel-like-factor-17-inhibits-urokinase-plasminogen-activator-gene-expression-to-suppress-cell-invasion-through-the-src-p38-mapk-signaling-pathway-in-human-lung-adenocarcionma
#17
Xing-Dong Cai, Li Che, Jia-Xin Lin, Shuai Huang, Jiong Li, Xiao-Yan Liu, Xing-Fei Pan, Qin-Qin Wang, Li Chen, Ming-Juan Lin, Zhi-Hong Huang, Hong-Ming Ma, Yi Wu, Sheng-Ming Liu, Yan-Bin Zhou
Krüppel-like factor 17 (KLF17) has been reported to be involved in invasion and metastasis suppression in lung cancer, but the molecular mechanisms underlying the anti-invasion and anti-metastasis roles of KLF17 in lung cancer are not fully illustrated. Here, we showed that KLF17 inhibited the invasion of A549 and H322 cells; the anti-invasion effect of KLF17 was associated with the suppression of urokinase plasminogen activator (uPA/PLAU) expression. KLF17 can bind with the promoter of uPA and inhibit its expression...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28451751/natriuretic-peptide-activation-of-extracellular-regulated-kinase-1-2-erk1-2-pathway-by-particulate-guanylyl-cyclases-in-gh3-somatolactotropes
#18
Kim C Jonas, Timothy Melrose, Iain R Thompson, Gary F Baxter, Victoria J Lipscomb, Stijn J Niessen, Charlotte Lawson, Craig A McArdle, Mark S Roberson, Imelda M McGonnell, Caroline P Wheeler-Jones, Robert C Fowkes
The natriuretic peptides, Atrial-, B-type and C-type natriuretric peptides (ANP, BNP, CNP), are regulators of many endocrine tissues and exert their effects predominantly through the activation of their specific guanylyl cyclase receptors (GC-A and GC-B) to generate cGMP. Whereas cGMP-independent signalling has been reported in response to natriuretic peptides, this is mediated via either the clearance receptor (Npr-C) or a renal-specific NPR-Bi isoform, which both lack intrinsic guanylyl cyclase activity. Here, we report evidence of GC-B-dependent cGMP-independent signalling in pituitary GH3 cells...
April 27, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28423613/secreted-grp78-activates-egfr-src-stat3-signaling-and-confers-the-resistance-to-sorafeinib-in-hcc-cells
#19
Rui Li, Gu Yanjiao, He Wubin, Wang Yue, Huang Jianhua, Zheng Huachuan, Su Rongjian, Luan Zhidong
Acquired resistance is a common phenomenon for HCC patients who undergone sorafenib treatment, however the mechanism by which acquired resistance develops remains elusive. In this study, we found that GRP78 could be detected in the serum samples of HCC patients and the conditional medium of multiple HCC cell lines, suggesting that GRP78 is secreted by HCC cells. Further studies showed that secreted GRP78 facilitated the proliferation and inhibited the apoptosis induced by sorafenib both in HCC cell lines and in tumor xenografts...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419476/cortactin-a-lyn-substrate-is-a-checkpoint-molecule-at-the-intersection-of-bcr-and-cxcr4-signalling-pathway-in-chronic-lymphocytic-leukaemia-cells
#20
Veronica Martini, Cristina Gattazzo, Federica Frezzato, Valentina Trimarco, Marco Pizzi, Giorgia Chiodin, Filippo Severin, Edoardo Scomazzon, Vincenza Guzzardo, Deborah Saraggi, Flavia Raggi, Leonardo Martinello, Monica Facco, Andrea Visentin, Francesco Piazza, Anna Maria Brunati, Gianpietro Semenzato, Livio Trentin
Cortactin (CTTN) is a substrate of the Src kinase Lyn that is known to play an actin cytoskeletal regulatory role involved in cell migration and cancer progression following its phosphorylation at Y421. We recently demonstrated that Cortactin is overexpressed in patients with chronic lymphocytic leukaemia (CLL). This work was aimed at defining the functional role of Cortactin in these patients. We found that Cortactin is variably expressed in CLL patients both in the peripheral blood and lymph nodes and that its expression correlates with the release of matrix metalloproteinase 9 (MMP-9) and the motility of neoplastic cells...
April 17, 2017: British Journal of Haematology
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