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https://www.readbyqxmd.com/read/27381982/protein-kinase-b-akt-regulates-syk-activity-and-shuttling-through-14-3-3-and-importin-7
#1
Dara K Mohammad, Beston F Nore, Manuela O Gustafsson, Abdalla J Mohamed, C I Edvard Smith
The Protein kinase B (AKT) regulates a plethora of intracellular signaling proteins to fine-tune signaling of multiple pathways. Here, we found that following B-cell receptor (BCR)-induced tyrosine phosphorylation of the cytoplasmic tyrosine kinase SYK and the adaptor BLNK, the AKT/PKB enzyme strongly induced BLNK (>100-fold) and SYK (>100-fold) serine/threonine phosphorylation (pS/pT). Increased phosphorylation promoted 14-3-3 binding to BLNK (37-fold) and SYK (2.5-fold) in a pS/pT-concentration dependent manner...
September 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27258042/dual-role-of-the-tyrosine-kinase-syk-in-regulation-of-toll-like-receptor-signaling-in-plasmacytoid-dendritic-cells
#2
Besma Aouar, Denisa Kovarova, Sebastien Letard, Albert Font-Haro, Jonathan Florentin, Jan Weber, David Durantel, Laurence Chaperot, Joel Plumas, Katerina Trejbalova, Jiri Hejnar, Jacques A Nunès, Daniel Olive, Patrice Dubreuil, Ivan Hirsch, Ruzena Stranska
Crosslinking of regulatory immunoreceptors (RR), such as BDCA-2 (CD303) or ILT7 (CD85g), of plasmacytoid dendritic cells (pDCs) efficiently suppresses production of type-I interferon (IFN)-α/β and other cytokines in response to Toll-like receptor (TLR) 7/9 ligands. This cytokine-inhibitory pathway is mediated by spleen tyrosine kinase (Syk) associated with the ITAM-containing adapter of RR. Here we demonstrate by pharmacological targeting of Syk that in addition to the negative regulation of TLR7/9 signaling via RR, Syk also positively regulates the TLR7/9 pathway in human pDCs...
2016: PloS One
https://www.readbyqxmd.com/read/27177528/therapeutic-benefits-of-spleen-tyrosine-kinase-inhibitor-administration-on-binge-drinking-induced-alcoholic-liver-injury-steatosis-and-inflammation-in-mice
#3
Terence N Bukong, Arvin Iracheta-Vellve, Benedek Gyongyosi, Aditya Ambade, Donna Catalano, Karen Kodys, Gyongyi Szabo
BACKGROUND: Binge drinking is increasingly recognized as an important cause of liver disease with limited therapeutic options for patients. Binge alcohol use, similar to chronic alcohol consumption, induces numerous deregulated signaling events that drive liver damage, steatosis, and inflammation. In this article, we evaluated the role of spleen tyrosine kinase (SYK), which modulates numerous signaling events previously identified linked in the development alcohol-induced liver pathology...
July 2016: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/26251216/myeloid-cell-mediated-renal-injury-in-rapidly-progressive-glomerulonephritis-depends-upon-spleen-tyrosine-kinase
#4
Jessica Ryan, Frank Y Ma, Yingjie Han, Elyce Ozols, John Kanellis, Greg H Tesch, David J Nikolic-Paterson
Antibody-dependent activation of myeloid cells within the glomerulus plays a central role in rapidly progressive forms of glomerulonephritis. The spleen tyrosine kinase (Syk) is expressed by all leukocytes, except mature T cells, and is required for signalling via the B-cell receptor, Fc receptors, and some integrins. Syk has been proposed as a therapeutic target in glomerulonephritis. However, little is known of Syk activation in human kidney disease, while studies in experimental glomerulonephritis using non-selective Syk inhibitors require validation via conditional gene deletion...
January 2016: Journal of Pathology
https://www.readbyqxmd.com/read/25462818/c-type-lectin-like-receptor-2-clec-2-signals-independently-of-lipid-raft-microdomains-in-platelets
#5
Bhanu Kanth Manne, Rachit Badolia, Carol A Dangelmaier, Satya P Kunapuli
C-type lectin like receptor 2 (CLEC-2) has been reported to activate platelets through a lipid raft-dependent manner. Secreted ADP potentiates CLEC-2-mediated platelet aggregation. We have investigated whether the decrease in CLEC-2-mediated platelet aggregation, previously reported in platelets with disrupted rafts, is a result of the loss of agonist potentiation by ADP. We disrupted platelet lipid rafts with methyl-β-cyclodextrin (MβCD) and measured signaling events downstream of CLEC-2 activation. Lipid raft disruption decreases platelet aggregation induced by CLEC-2 agonists...
January 15, 2015: Biochemical Pharmacology
https://www.readbyqxmd.com/read/23960082/tyrosine-phosphorylation-on-spleen-tyrosine-kinase-syk-is-differentially-regulated-in-human-and-murine-platelets-by-protein-kinase-c-isoforms
#6
Lorena Buitrago, Dheeraj Bhavanasi, Carol Dangelmaier, Bhanu Kanth Manne, Rachit Badolia, Alessandra Borgognone, Alexander Y Tsygankov, Steven E McKenzie, Satya P Kunapuli
Protein kinase C (PKC) isoforms differentially regulate platelet functional responses downstream of glycoprotein VI (GPVI) signaling, but the role of PKCs regulating upstream effectors such as Syk is not known. We investigated the role of PKC on Syk tyrosine phosphorylation using the pan-PKC inhibitor GF109203X (GFX). GPVI-mediated phosphorylation on Syk Tyr-323, Tyr-352, and Tyr-525/526 was rapidly dephosphorylated, but GFX treatment inhibited this dephosphorylation on Tyr-525/526 in human platelets but not in wild type murine platelets...
October 4, 2013: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/23696510/population-based-data-from-the-swedish-colon-cancer-registry
#7
K Kodeda, L Nathanaelsson, B Jung, H Olsson, P Jestin, A Sjövall, B Glimelius, L Påhlman, I Syk
BACKGROUND: Evaluating the external validity of clinical trials requires knowledge not only of the study population but also of a relevant reference population. The main aim of this study was to present data from a large, contemporary, population-based cohort of patients with colonic cancer. METHODS: Data on patients diagnosed between 2007 and 2011 were extracted from the Swedish Colon Cancer Registry. The data, registered prospectively in a national population of almost 10 million, included over 99 per cent of all diagnosed adenocarcinomas of the colon...
July 2013: British Journal of Surgery
https://www.readbyqxmd.com/read/23149425/tula-2-a-novel-histidine-phosphatase-regulates-bone-remodeling-by-modulating-osteoclast-function
#8
Steven H Back, Naga Suresh Adapala, Mary F Barbe, Nick C Carpino, Alexander Y Tsygankov, Archana Sanjay
Bone is a dynamic tissue that depends on the intricate relationship between protein tyrosine kinases (PTK) and protein tyrosine phosphatases (PTP) for maintaining homeostasis. PTKs and PTPs act like molecular on and off switches and help modulate differentiation and the attachment of osteoclasts to bone matrix regulating bone resorption. The protein T cell ubiquitin ligand-2 (TULA-2), which is abundantly expressed in osteoclasts, is a novel histidine phosphatase. Our results show that of the two family members, only TULA-2 is expressed in osteoclasts and that its expression is sustained throughout the course of osteoclast differentiation, suggesting that TULA-2 may play a role during early as well late stages of osteoclast differentiation...
April 2013: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/22460711/an-osteoclastic-protein-tyrosine-phosphatase-regulates-the-%C3%AE-3-integrin-syk-and-shp1-signaling-through-respective-src-dependent-phosphorylation-in-osteoclasts
#9
K-H William Lau, Virginia Stiffel, Mehran Amoui
This study utilized the glutathione transferase (GST) pull-down assay to identify novel substrates of an osteoclastic protein-tyrosine phosphatase, PTP-oc. Consistent with the previous findings that the phosphorylated tyr-527 (pY527) of Src is a substrate of PTP-oc, the major protein pulled down with the phosphatase-deficient (PD)-PTP-oc-GST trapping mutant in RAW264.7 cells was Src. The GST-PD-PTP-oc also pulled down pY-Syk and pY-β(3)-integrin, but not after PP2 pretreatment. However, PTP-oc transgenic osteoclasts or PTP-oc-overexpressing RAW264...
June 1, 2012: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/22330086/inhibitory-effects-of-an-ellagic-acid-glucoside-okicamelliaside-on-antigen-mediated-degranulation-in-rat-basophilic-leukemia-rbl-2h3-cells-and-passive-cutaneous-anaphylaxis-reaction-in-mice
#10
Megumi Kuba-Miyara, Kengo Agarie, Rina Sakima, Shihoko Imamura, Kazuyo Tsuha, Takeshi Yasumoto, Shinichi Gima, Goro Matsuzaki, Tsuyoshi Ikehara
Degranulation inhibitors in plants are widely used for prevention and treatment of immediate-type allergy. We previously isolated a new ellagic acid glucoside, okicamelliaside (OCS), from Camellia japonica leaves for use as a potent degranulation inhibitor. Crude extracts from leaves also suppressed allergic conjunctivitis in rats. In this study, we evaluated the in vivo effect of OCS using a pure sample and performed in vitro experiments to elucidate the mechanism underlying the extraordinary high potency of OCS and its aglycon...
April 2012: International Immunopharmacology
https://www.readbyqxmd.com/read/21894146/spleen-tyrosine-kinase-promotes-acute-neutrophil-mediated-glomerular-injury-via-activation-of-jnk-and-p38-mapk-in-rat-nephrotoxic-serum-nephritis
#11
Jessica Ryan, Frank Y Ma, John Kanellis, Mercedes Delgado, Kate Blease, David J Nikolic-Paterson
Glomerular antibody deposition induces acute neutrophil-mediated glomerular injury via activation of c-Jun amino terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). However, the link between antibody deposition and activation of JNK/p38 MAPK signalling is unclear. This study tested the postulate that spleen tyrosine kinase (Syk), which is activated via Fcγ-receptor ligation, is required for activation of JNK and p38 signalling and acute neutrophil-mediated glomerular injury. We used a Syk inhibitor (SYKi) in rat nephrotoxic serum nephritis (NTN) in which neutrophil-mediated glomerular injury is dependent upon JNK and p38 signalling...
December 2011: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/20670933/determination-of-the-substrate-specificity-of-protein-tyrosine-phosphatase-tula-2-and-identification-of-syk-as-a-tula-2-substrate
#12
Xianwen Chen, Lige Ren, Soochong Kim, Nicholas Carpino, James L Daniel, Satya P Kunapuli, Alexander Y Tsygankov, Dehua Pei
TULA-1 (UBASH3A/STS-2) and TULA-2 (p70/STS-1) represent a novel class of protein-tyrosine phosphatases. Previous studies suggest that TULA-2 is sequence-selective toward phosphotyrosyl (Tyr(P)) peptides. In this work the substrate specificity of TULA-1 and -2 was systematically evaluated by screening a combinatorial Tyr(P) peptide library. Although TULA-1 showed no detectable activity toward any of the Tyr(P) peptides in the library, TULA-2 recognizes two distinct classes of Tyr(P) substrates. On the N-terminal side of Tyr(P), the class I substrates contain a proline at the Tyr(P)-1 position, a hydrophilic residue at the Tyr(P)-2 position, and aromatic hydrophobic residues at positions Tyr(P)-3 and beyond...
October 8, 2010: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/20013945/human-spleen-tyrosine-kinase-syk-recombinant-expression-systems-for-high-throughput-assays
#13
COMPARATIVE STUDY
Deepika Singh, Reema Rani, Resmi Rajendran, Namrata Jit Kaur, Abhinav Pandey, Puneet Chopra, Tarun Jain, Manish Kumar Jain, Sonam Grover, Ranjana Arya, Kulvinder Singh Saini
Spleen tyrosine kinase (Syk) is an important non-receptor tyrosine kinase and its aberrant regulation is associated with a variety of allergic disorders and autoimmune diseases. To identify small molecule inhibitors of Syk in high-throughput assays, recombinant Syk protein is needed in bulk quantity. We studied the expression of recombinant human Syk in three heterologous systems: E. coli, baculovirus expression vector system (BEVS), and the cellular slime mold Dictyostelium discoideum (Dd). Syk activity was higher in the BEVS as compared to the Dd expression host, whereas in E...
February 2010: Biotechnology Journal
https://www.readbyqxmd.com/read/19296913/phosphorylation-of-the-activation-loop-tyrosines-is-required-for-sustained-syk-signaling-and-growth-factor-independent-b-cell-proliferation
#14
Laura Carsetti, Luca Laurenti, Stefania Gobessi, Pablo G Longo, Giuseppe Leone, Dimitar G Efremov
The Syk kinase is regarded as a promising target for the treatment of antigen-driven B-cell malignancies, considering its essential role in propagating antigenic stimuli through the B-cell receptor (BCR). In certain common B-cell malignancies Syk is activated even in the absence of BCR engagement, suggesting a wider role for this kinase in lymphomagenesis. In this paper, we have profiled molecular differences between BCR-induced and constitutive Syk activation in terms of phosphorylation of regulatory tyrosine residues, downstream signaling properties and capacity to sustain B-cell proliferation...
July 2009: Cellular Signalling
https://www.readbyqxmd.com/read/19012179/hematopoietic-lineage-cell-specific-protein-1-hs1-regulates-par-mediated-erk-activation-and-thromboxane-generation-in-platelets
#15
Bryan N Kahner, Robert T Dorsam, Soochong Kim, Haripriya Shankar, Daisuke Kitamura, Satya P Kunapuli
Thrombin-induced platelet activation leads to tyrosine phosphorylation of hematopoietic lineage cell-specific protein-1 (HS1), a 75 kDa adapter protein expressed exclusively in cells of hematopoietic lineage. We have shown HS1 to be a functionally important signaling molecule downstream of PAR-4 and GPVI collagen receptor. We have thus begun to elucidate PAR signaling pathway of HS1 phosphorylation, and its functional implications. PAR-1 and PAR-4 activating peptides (SFLLRN and AYPGKF, respectively) induced HS1 phosphorylation in a Gq-dependent manner as shown by incubation with the Gq inhibitor, YM254890...
December 2008: Platelets
https://www.readbyqxmd.com/read/18715989/platelets-undergo-phosphorylation-of-syk-at-y525-526-and-y352-in-response-to-pathophysiological-shear-stress
#16
Henry E Speich, Svetozar Grgurevich, Teddi J Kueter, Angela D Earhart, Steven M Slack, Lisa K Jennings
Atherosclerotic plaques can lead to partial vascular occlusions that produce abnormally high levels of arterial wall shear stress. Such pathophysiological shear stress can promote shear-induced platelet aggregation (SIPA), which has been linked to acute myocardial infarction, unstable angina, and stroke. This study investigated the role of the tyrosine kinase Syk in shear-induced human platelet signaling. The extent of Syk tyrosine phosphorylation induced by pathophysiological levels of shear stress (100 dyn/cm(2)) was significantly greater than that resulting from physiological shear stress (10 dyn/cm(2))...
October 2008: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/18401419/overexpression-of-syk-tyrosine-kinase-in-peripheral-t-cell-lymphomas
#17
A L Feldman, D X Sun, M E Law, A J Novak, A D Attygalle, E C Thorland, S R Fink, J A Vrana, B L Caron, W G Morice, E D Remstein, K L Grogg, P J Kurtin, W R Macon, A Dogan
Peripheral T-cell lymphomas (PTCLs) are fatal in the majority of patients and novel treatments, such as protein tyrosine kinase (PTK) inhibition, are needed. The recent finding of SYK/ITK translocations in rare PTCLs led us to examine the expression of Syk PTK in 141 PTCLs. Syk was positive by immunohistochemistry (IHC) in 133 PTCLs (94%), whereas normal T cells were negative. Western blot on frozen tissue (n=6) and flow cytometry on cell suspensions (n=4) correlated with IHC results in paraffin. Additionally, western blot demonstrated that Syk-positive PTCLs show tyrosine (525/526) phosphorylation, known to be required for Syk activation...
June 2008: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/18362147/activation-of-syk-by-protein-kinase-c-delta-regulates-thrombin-induced-intercellular-adhesion-molecule-1-expression-in-endothelial-cells-via-tyrosine-phosphorylation-of-rela-p65
#18
Kaiser M Bijli, Fabeha Fazal, Mohd Minhajuddin, Arshad Rahman
Protein kinase C-delta (PKC-delta) plays a pivotal role in mediating thrombin-induced NF-kappaB activation and ICAM-1 expression in endothelial cells. However, the downstream mechanisms mediating its function are unclear. In this study, we show that PKC-delta-mediated activation of protein-tyrosine kinase Syk plays an important role in thrombin signaling of NF-kappaB activation and intercellular adhesion molecule-1 (ICAM-1) expression in endothelial cells. Stimulation of human vascular endothelial cells with thrombin resulted in a time-dependent phosphorylation of Syk on tyrosine 525 and 526, an indication of Syk activation...
May 23, 2008: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/18006696/syk-dependent-tonic-b-cell-receptor-signaling-is-a-rational-treatment-target-in-diffuse-large-b-cell-lymphoma
#19
Linfeng Chen, Stefano Monti, Przemyslaw Juszczynski, John Daley, Wen Chen, Thomas E Witzig, Thomas M Habermann, Jeffery L Kutok, Margaret A Shipp
The role of B-cell receptor (BCR)-mediated survival signals in diffuse large B-cell lymphoma (DLBCL) remains undefined. Ligand-induced BCR signaling induces receptor oligomerization, Igalpha/beta immunoreceptor tyrosine-based activation motif (ITAM) phosphorylation, and activation of the spleen tyrosine kinase (SYK), which initiates downstream events and amplifies the initial BCR signal. BCRs also transmit low-level tonic survival signals in the absence of receptor engagement. Herein, we assess the role of SYK-dependent tonic BCR survival signals in DLBCL cell lines and primary tumors and evaluate the efficacy of an ATP-competitive inhibitor of SYK, R406, in vitro...
February 15, 2008: Blood
https://www.readbyqxmd.com/read/15457545/a-cyclic-adenosine-3-5-monophosphate-induced-tyrosine-phosphorylation-of-syk-protein-tyrosine-kinase-in-the-flagella-of-boar-spermatozoa
#20
Hiroshi Harayama, Mai Muroga, Masashi Miyake
A cyclic adenosine 3',5'-monophosphate (cAMP)-dependent protein tyrosine phosphorylation is involved in the expression of fertilizing ability in mammalian spermatozoa. However, there are only limited data concerning the identification of protein tyrosine kinase (PTK) that is activated by the cAMP signaling. In this study, we have shown data supporting that boar sperm flagellum possesses a unique cAMP-protein kinase A (PKA) signaling cascade leading to phosphorylation of Syk PTK at the tyrosine residues of the activation loop...
December 2004: Molecular Reproduction and Development
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