Read by QxMD icon Read

Phospholipase C gamma 2 tyrosine

Ana Saavedra, Mar Puigdellívol, Shiraz Tyebji, Pradeep Kurup, Jian Xu, Silvia Ginés, Jordi Alberch, Paul J Lombroso, Esther Pérez-Navarro
Brain-derived neurotrophic factor (BDNF) promotes synaptic strengthening through the regulation of kinase and phosphatase activity. Conversely, striatal-enriched protein tyrosine phosphatase (STEP) opposes synaptic strengthening through inactivation or internalization of signaling molecules. Here, we investigated whether BDNF regulates STEP levels/activity. BDNF induced a reduction of STEP61 levels in primary cortical neurons, an effect that was prevented by inhibition of tyrosine kinases, phospholipase C gamma, or the ubiquitin-proteasome system (UPS)...
August 2016: Molecular Neurobiology
Ta-Ming Liu, Jennifer A Woyach, Yiming Zhong, Arletta Lozanski, Gerard Lozanski, Shuai Dong, Ethan Strattan, Amy Lehman, Xiaoli Zhang, Jeffrey A Jones, Joseph Flynn, Leslie A Andritsos, Kami Maddocks, Samantha M Jaglowski, Kristie A Blum, John C Byrd, Jason A Dubovsky, Amy J Johnson
Ibrutinib has significantly improved the outcome of patients with relapsed chronic lymphocytic leukemia (CLL). Recent reports attribute ibrutinib resistance to acquired mutations in Bruton agammaglobulinemia tyrosine kinase (BTK), the target of ibrutinib, as well as the immediate downstream effector phospholipase C, γ2 (PLCG2). Although the C481S mutation found in BTK has been shown to disable ibrutinib's capacity to irreversibly bind this primary target, the detailed mechanisms of mutations in PLCG2 have yet to be established...
July 2, 2015: Blood
T M Schnöder, P Arreba-Tutusaus, I Griehl, L Bullinger, M Buschbeck, S W Lane, K Döhner, C Plass, D B Lipka, F H Heidel, T Fischer
Erythropoiesis is a tightly regulated process. Development of red blood cells occurs through differentiation of hematopoietic stem cells (HSCs) into more committed progenitors and finally into erythrocytes. Binding of erythropoietin (Epo) to its receptor (EpoR) is required for erythropoiesis as it promotes survival and late maturation of erythroid progenitors. In vivo and in vitro studies have highlighted the requirement of EpoR signaling through Janus kinase 2 (Jak2) tyrosine kinase and Stat5a/b as a central pathway...
June 2015: Cell Death and Differentiation
Susan Li, Christine H Miller, Eugenia Giannopoulou, Xiaoyu Hu, Lionel B Ivashkiv, Baohong Zhao
Osteoclastogenesis requires activation of RANK signaling as well as costimulatory signals from immunoreceptor tyrosine-based activation motif-containing (ITAM-containing) receptors/adaptors, predominantly tyrosine kinase-binding proteins DAP12 and FcRγ, in osteoclast precursors. It is not well understood how costimulatory signals are regulated and integrated with RANK signaling. Here, we found that osteopetrotic bone phenotypes in mice lacking DAP12 or DAP12 and FcRγ are mediated by the transcription factor RBP-J, as deletion of Rbpj in these mice substantially rescued the defects of bone remodeling...
November 2014: Journal of Clinical Investigation
Corinna Lehnert, Maxi Weiswange, Irmela Jeremias, Carina Bayer, Michaela Grunert, Klaus-Michael Debatin, Gudrun Strauss
The TRAIL-receptor/TRAIL system originally described to induce apoptosis preferentially in malignant cells is also known to be involved in T cell homeostasis and the response to viral infections and autoimmune diseases. Whereas the expression of TRAIL on activated NK and T cells increases their cytotoxicity, induction of TRAIL on APCs can turn them into apoptosis inducers but might also change their immunostimulatory capacity. Therefore, we analyzed how TRAIL-receptor (TRAIL-R) costimulation is modulating TCR-mediated activation of human T cells...
October 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Musaed M Alshahrani, Eunice Yang, Jana Yip, Simona S Ghanem, Simon L Abdallah, Anthony M deAngelis, Cindy J O'Malley, Fatemeh Moheimani, Sonia M Najjar, Denise E Jackson
Carcinoembryonic antigen-related cell adhesion molecule-2 (CEACAM2) is a cell-surface glycoprotein expressed on blood, epithelial, and vascular cells. CEACAM2 possesses adhesive and signaling properties mediated by immunoreceptor tyrosine-based inhibitory motifs. In this study, we demonstrate that CEACAM2 is expressed on the surface and in intracellular pools of platelets. Functional studies of platelets from Ceacam2(-/-)-deficient mice (Cc2(-/-)) revealed that CEACAM2 serves to negatively regulate collagen glycoprotein VI (platelet) (GPVI)-FcRγ-chain and the C-type lectinlike receptor 2 (CLEC-2) signaling...
October 9, 2014: Blood
R Wang, P Zhang, Y Wang, L Zhang
OBJECTIVE: This study aimed to examine the mechanism of Tα146-162-iMDC in the pathogenic intervention of mice with experimental autoimmune myasthenia gravis (EAMG) from the perspective of B-cell activation. MATERIALS AND METHODS: The mice were divided into three groups, model (A), intervention (B), and control (C), with the intervention of Tα146-162-iMDC. The expressions of Cbl-b mRNA, Syk, Lyn, Btk, and phospholipase C (PLC)-γ2 proteins and their phosphorylated proteins were detected...
2014: European Review for Medical and Pharmacological Sciences
Jennifer A Woyach, Richard R Furman, Ta-Ming Liu, Hatice Gulcin Ozer, Marc Zapatka, Amy S Ruppert, Ling Xue, Daniel Hsieh-Hsin Li, Susanne M Steggerda, Matthias Versele, Sandeep S Dave, Jenny Zhang, Ayse Selen Yilmaz, Samantha M Jaglowski, Kristie A Blum, Arletta Lozanski, Gerard Lozanski, Danelle F James, Jacqueline C Barrientos, Peter Lichter, Stephan Stilgenbauer, Joseph J Buggy, Betty Y Chang, Amy J Johnson, John C Byrd
BACKGROUND: Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (BTK) and is effective in chronic lymphocytic leukemia (CLL). Resistance to irreversible kinase inhibitors and resistance associated with BTK inhibition have not been characterized. Although only a small proportion of patients have had a relapse during ibrutinib therapy, an understanding of resistance mechanisms is important. We evaluated patients with relapsed disease to identify mutations that may mediate ibrutinib resistance...
June 12, 2014: New England Journal of Medicine
Wei-Zhong Ying, Kristal J Aaron, Paul W Sanders
The amount of Na(+) and K(+) in the diet promotes significant changes in endothelial cell function. In the present study, a series of in vitro and in vivo experiments determined the role of Na(+) and K(+) in the regulation of two pleckstrin homology domain-containing intracellular signaling molecules, phospholipase C (PLC)-γ1 and epithelial and endothelial tyrosine kinase/bone marrow tyrosine kinase on chromosome X (Bmx), and agonist-generated Ca(2+) signaling in the endothelium. Extracellular K(+) concentration regulated the levels of activated PLC-γ1, Bmx, and carbachol-stimulated intracellular Ca(2+) mobilization in human endothelial cells...
July 1, 2014: American Journal of Physiology. Renal Physiology
Wen Liu, Mei-Juan Cai, Chuan-Chuan Zheng, Jin-Xing Wang, Xiao-Fan Zhao
In addition to the classical nuclear receptor pathway, there is a nongenomic pathway in the cell membrane that regulates gene expression in animal steroid hormone signaling; however, this mechanism is unclear. Here, we report that the insect steroid hormone 20-hydroxyecdysone (20E) regulates calcium influx via phospholipase Cγ1 (PLCG1) to modulate the protein kinase C phosphorylation of the transcription factor ultraspiracle (USP1) in the lepidopteran insect Helicoverpa armigera. The PLCG1 mRNA levels are increased during the molting and metamorphic stages...
May 9, 2014: Journal of Biological Chemistry
Luis-Alberto Pérez-Quintero, Romain Roncagalli, Huaijian Guo, Sylvain Latour, Dominique Davidson, André Veillette
Ewing's sarcoma-associated transcript 2 (EAT-2) is an Src homology 2 domain-containing intracellular adaptor related to signaling lymphocytic activation molecule (SLAM)-associated protein (SAP), the X-linked lymphoproliferative gene product. Both EAT-2 and SAP are expressed in natural killer (NK) cells, and their combined expression is essential for NK cells to kill abnormal hematopoietic cells. SAP mediates this function by coupling SLAM family receptors to the protein tyrosine kinase Fyn and the exchange factor Vav, thereby promoting conjugate formation between NK cells and target cells...
April 7, 2014: Journal of Experimental Medicine
Timothy J Wilson, Lee I Garner, Clive Metcalfe, Elliott King, Stefanie Margraf, Marion H Brown
SLAM family receptors regulate activation and inhibition in immunity through recruitment of activating and inhibitory SH2 domain containing proteins to immunoreceptor tyrosine based switch motifs (ITSMs). Binding of the adaptors, SAP and EAT-2 to ITSMs in the cytoplasmic regions of SLAM family receptors is important for activation. We analysed the fine specificity of SLAM family receptor phosphorylated ITSMs and the conserved tyrosine motif in EAT-2 for SH2 domain containing signalling proteins. Consistent with the literature describing dependence of CRACC (SLAMF7) on EAT-2, CRACC bound EAT-2 (KD = 0...
2014: PloS One
M Lia Palomba, Kelly Piersanti, Carly G K Ziegler, Hugo Decker, Jesse W Cotari, Kurt Bantilan, Ivelise Rijo, Jeff R Gardner, Mark Heaney, Debra Bemis, Robert Balderas, Sami N Malek, Erlene Seymour, Andrew D Zelenetz, Marcel R M van den Brink, Grégoire Altan-Bonnet
PURPOSE: Chronic Lymphocytic Leukemia (CLL) is defined by a perturbed B-cell receptor-mediated signaling machinery. We aimed to model differential signaling behavior between B cells from CLL and healthy individuals to pinpoint modes of dysregulation. EXPERIMENTAL DESIGN: We developed an experimental methodology combining immunophenotyping, multiplexed phosphospecific flow cytometry, and multifactorial statistical modeling. Utilizing patterns of signaling network covariance, we modeled BCR signaling in 67 CLL patients using Partial Least Squares Regression (PLSR)...
2014: PloS One
Alejandro Zimman, Bjoern Titz, Evangelia Komisopoulou, Sudipta Biswas, Thomas G Graeber, Eugene A Podrez
Specific oxidized phospholipids (oxPCCD36) promote platelet hyper-reactivity and thrombosis in hyperlipidemia via the scavenger receptor CD36, however the signaling pathway(s) induced in platelets by oxPCCD36 are not well defined. We have employed mass spectrometry-based tyrosine, serine, and threonine phosphoproteomics for the unbiased analysis of platelet signaling pathways induced by oxPCCD36 as well as by the strong physiological agonist thrombin. oxPCCD36 and thrombin induced differential phosphorylation of 115 proteins (162 phosphorylation sites) and 181 proteins (334 phosphorylation sites) respectively...
2014: PloS One
A-Young Choi, Ji Hyun Choi, Keun-Young Hwang, Yeon Ju Jeong, Wonchae Choe, Kyung-Sik Yoon, Joohun Ha, Sung Soo Kim, Jang Hyun Youn, Eui-Ju Yeo, Insug Kang
Licochalcone A (LicA), an estrogenic flavonoid, induces apoptosis in multiple types of cancer cells. In this study, the molecular mechanisms underlying the anti-cancer effects of LicA were investigated in HepG2 human hepatocellular carcinoma cells. LicA induced apoptotic cell death, activation of caspase-4, -9, and -3, and expression of endoplasmic reticulum (ER) stress-associated proteins, including C/EBP homologous protein (CHOP). Inhibition of ER stress by CHOP knockdown or treatment with the ER stress inhibitors, salubrinal and 4-phenylbutyric acid, reduced LicA-induced cell death...
April 2014: Apoptosis: An International Journal on Programmed Cell Death
Ryan C Bates, Colby P Fees, William L Holland, Courtney C Winger, Khulan Batbayar, Rachel Ancar, Todd Bergren, Douglas Petcoff, Bradley J Stith
We report a new step in the fertilization in Xenopus laevis which has been found to involve activation of Src tyrosine kinase to stimulate phospholipase C-γ (PLC-γ) which increases inositol 1,4,5-trisphosphate (IP3) to release intracellular calcium ([Ca](i)). Molecular species analysis and mass measurements suggested that sperm activate phospholipase D (PLD) to elevate phosphatidic acid (PA). We now report that PA mass increased 2.7 fold by 1 min after insemination and inhibition of PA production by two methods inhibited activation of Src and PLCγ, increased [Ca](i) and other fertilization events...
February 1, 2014: Developmental Biology
Knut Fälker, Kristin Klarström-Engström, Torbjörn Bengtsson, Tomas L Lindahl, Magnus Grenegård
The specific TLR2/1 complex activator Pam3CSK4 has been shown to provoke prominent activation and aggregation of human non-nucleated platelets. As Pam3CSK4-evoked platelet activation does not employ the major signalling pathway established in nucleated immune cells, we investigated if the TLR2/1 complex on platelets may initiate signalling pathways known to be induced by physiological agonists such as collagen via GPVI or thrombin via PARs. We found that triggering TLR2/1 complex-signalling with Pam3CSK4, in common with that induced via GPVI, and in contrast to that provoked by PARs, involves tyrosine phosphorylation of the adaptor protein LAT as well as of PLCγ2 in a src- and Syk-dependent manner...
February 2014: Cellular Signalling
Michael Engelke, Thomas Oellerich, Kai Dittmann, He-Hsuan Hsiao, Henning Urlaub, Hubert Serve, Christian Griesinger, Jürgen Wienands
Ag-mediated B cell stimulation relies on phospholipase Cγ2 (PLCγ2) for Ca(2+) mobilization. Enzymatic activity of PLCγ2 is triggered upon Src homology 2 domain-mediated binding to the tyrosine-phosphorylated adaptor SLP65. However, SLP65 phosphorylation outlasts the elevation of cytosolic Ca(2+) concentration suggesting additional levels of PLCγ2 regulation. We show in this article that the functionality of the PLCγ2/SLP65 complex is controlled by the weakly characterized C2 domain of PLCγ2. Usually C2 domains bind membrane lipids, but that of PLCγ2 docks in a Ca(2+)-regulated manner to a distinct phosphotyrosine of SLP65...
December 1, 2013: Journal of Immunology: Official Journal of the American Association of Immunologists
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
Olga Novokhatska, Mykola Dergai, Liudmyla Tsyba, Inessa Skrypkina, Valeriy Filonenko, Jacques Moreau, Alla Rynditch
BACKGROUND: Scaffolding proteins of the intersectin (ITSN) family, ITSN1 and ITSN2, are crucial for the initiation stage of clathrin-mediated endocytosis. These proteins are closely related but have implications in distinct pathologies. To determine how these proteins could be separated in certain cell pathways we performed a comparative study of ITSNs. METHODOLOGY/PRINCIPAL FINDINGS: We have shown that endogenous ITSN1 and ITSN2 colocalize and form a complex in cells...
2013: PloS One
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"