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PLC gamma

Yekaterina B Khotskaya, Vijaykumar R Holla, Anna F Farago, Kenna R Mills Shaw, Funda Meric-Bernstam, David S Hong
The tropomyosin receptor kinase (TRK) family includes TRKA, TRKB, and TRKC proteins, which are encoded by NTRK1, NTRK2 and NTRK3 genes, respectively. Binding of neurotrophins to TRK proteins induces receptor dimerization, phosphorylation, and activation of the downstream signaling cascades via PI3K, RAS/MAPK/ERK, and PLC-gamma. TRK pathway aberrations, including gene fusions, protein overexpression, and single nucleotide alterations, have been implicated in the pathogenesis of many cancer types, with NTRK gene fusions being the most well validated oncogenic events to date...
February 4, 2017: Pharmacology & Therapeutics
Xi Chen, Xiao-Ming Li, Wen Gu, Di Wang, Yi Chen, Xue-Jun Guo
INTRODUCTION: Low expression of linker for activation of T cells (LAT) is observed in asthma. LAT and its downstream regulator, phospholipase C-gamma 1 (PLC-γ1) play important roles in the T cell antigen receptor signaling pathway, and their interaction is associated with CD4(+) cell polarization. Here, we investigated whether LAT can alleviate the imbalance among CD4(+) cell subgroups and the possible mechanism. METHODS: An ovalbumin-induced allergic asthma mouse model was established and LAT plasmid was delivered...
January 4, 2017: International Immunopharmacology
Soo Ji Woo, Hyae In Jo, Hyung Ho Lee, Joon Ki Chung
Phospholipase C gamma 1 and gamma 2 (PLCG1 and PLCG2) are influential in modulating Ca(2+) and diacylglycerol, second messengers involved in tyrosine kinase-dependent signaling, including growth factor activation. Here, we used RACE (rapid amplification of cDNA ends) to clone cDNA encoding PLCG1 (PoPLCG1) and PLCG2 (PoPLCG2) in the olive flounder (Paralichthys olivaceus). The respective 1313 and 1249 amino acid sequences share high identity with human PLCG1 and PLCG2, and contain the following domains: pleckstrin homology (PH), EF-hand, catalytic X and Y, Src homology 2 (SH2), Src homology 3 (SH3), and C2...
November 25, 2016: Fish & Shellfish Immunology
Hee-Sung Chae, Young-Mi Kim, Young-Won Chin
Atractylodin is one of the major constituents of the rhizome of Atractylodes lancea, which is widely used in Korean traditional medicine as a remedy for the treatment of gastritis and gastric ulcers. Despite of a major constituent of widely used botanical to treat inflammatory responses little is known about anti-inflammatory effect of atractylodin in the human mast cell (HMC-1). Hence, we evaluated the effect of atractylodin on the release of IL-6, the involvement of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) and mitogen-activated protein kinases (MAPKs) in phorbol-12-myristate-13-acetate and A23187-induced HMC-1...
September 2, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Evdoxia Karali, Sofia Bellou, Dimitris Stellas, Apostolos Klinakis, Carol Murphy, Theodore Fotsis
Vascular endothelial growth factor (VEGF) activates unfolded protein response sensors in the endoplasmic reticulum through phospholipase C gamma (PLCγ)-mediated crosstalk with mammalian target of rapamycin complex 1 (mTORC1). Activation of transcription factor 6 (ATF6) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) activate mTORC2, ensuring maximal endothelial cell survival and angiogenic activity through phosphorylation of AKT on Ser473. As mTORC1 is a metabolic sensor, metabolic signals may be integrated with signals from VEGF in the regulation of angiogenesis...
July 2014: Molecular & Cellular Oncology
Yuanxing Gu, Baozhu Qi, Yingshan Zhou, Xiaowu Jiang, Xian Zhang, Xiaoliang Li, Weihuan Fang
Porcine circovirus type 2 (PCV2) induces autophagy via the 5' adenosine monophosphate-activated protein kinase (AMPK)/extracellular signal-regulated kinase (ERK)/tuberous sclerosis complex 2 (TSC2)/mammalian target of rapamycin (mTOR) pathway in pig kidney PK-15 cells. However, the underlying mechanisms of AMPK activation in autophagy induction remain unknown. With specific inhibitors and RNA interference (RNAi), we show that PCV2 infection upregulated calcium/calmodulin-dependent protein kinase kinase-beta (CaMKKβ) by increasing cytosolic Ca(2+) via inositol 1,4,5-trisphosphate receptor (IP3R)...
2016: Viruses
Douglas C Palmer, Geoffrey C Guittard, Zulmarie Franco, Joseph G Crompton, Robert L Eil, Shashank J Patel, Yun Ji, Nicholas Van Panhuys, Christopher A Klebanoff, Madhusudhanan Sukumar, David Clever, Anna Chichura, Rahul Roychoudhuri, Rajat Varma, Ena Wang, Luca Gattinoni, Francesco M Marincola, Lakshmi Balagopalan, Lawrence E Samelson, Nicholas P Restifo
Improving the functional avidity of effector T cells is critical in overcoming inhibitory factors within the tumor microenvironment and eliciting tumor regression. We have found that Cish, a member of the suppressor of cytokine signaling (SOCS) family, is induced by TCR stimulation in CD8(+) T cells and inhibits their functional avidity against tumors. Genetic deletion of Cish in CD8(+) T cells enhances their expansion, functional avidity, and cytokine polyfunctionality, resulting in pronounced and durable regression of established tumors...
November 16, 2015: Journal of Experimental Medicine
Artem I Malomouzh, Konstantin A Petrov, Leniz F Nurullin, Evgeny E Nikolsky
Gamma-aminobutyric acid (GABA) is an amino acid which acts as a neurotransmitter in the central nervous system. Here, we studied the effects of GABA on non-quantal, spontaneous, and evoked quantal acetylcholine (ACh) release from motor nerve endings. We found that while the application of 10 μM of GABA had no effect on spontaneous quantal ACh release, as detected by the frequency of miniature endplate potentials, GABA reduced the non-quantal ACh release by 57%, as determined by the H-effect value. Finally, the evoked quantal ACh release, estimated by calculating the quantal content of full-sized endplate potentials (EPPs), was reduced by 34%...
December 2015: Journal of Neurochemistry
Askar M Akimzhanov, Darren Boehning
Palmitoylation is the posttranslational modification of proteins with a 16-carbon fatty acid chain through a labile thioester bond. The reversibility of protein palmitoylation and its profound effect on protein function suggest that this modification could play an important role as an intracellular signaling mechanism. Evidence that palmitoylation of proteins occurs with the kinetics required for signal transduction is not clear, however. Here we show that engagement of the Fas receptor by its ligand leads to an extremely rapid and transient increase in palmitoylation levels of the tyrosine kinase Lck...
September 22, 2015: Proceedings of the National Academy of Sciences of the United States of America
Jiafu Ji, Shuqin Jia, Yongning Jia, Ke Ji, Rachel Hargest, Wen G Jiang
BACKGROUND: It has recently been shown that WISP proteins (Wnt-inducted secreted proteins), a group of intra- and extra-cellular regulatory proteins, have been implicated in the initiation and progression of a variety of tumour types including colorectal and breast cancer. However, the role of WISP proteins in gastric cancer (GC) cells and their clinical implications have not yet been elucidated. METHODS: The expression of WISP molecules in a cohort of GC patients was analysed using real-time quantitative PCR and immunohistochemistry...
September 15, 2015: British Journal of Cancer
Miao Liu, Jarren C Kay, Shanwei Shen, Li-Ya Qiao
BACKGROUND: Spinal central sensitization is an important process in the generation and maintenance of visceral hypersensitivity. The release of brain-derived neurotrophic factor (BDNF) from the primary afferent neurons to the spinal cord contributes to spinal neuronal plasticity and increases neuronal activity and synaptic efficacy. The N-Methyl-D-aspartic acid (NMDA) receptor possesses ion channel properties, and its activity is modulated by phosphorylation of its subunits including the NMDA receptor 1 (NR1)...
August 20, 2015: Journal of Neuroinflammation
Meihua Gao, Lina Wang, Bing Wang, Beibei Cong, Shuchao Zhang
OBJECTIVE: To construct the lentivirus carrying the mutated palmitoylation site of the linker for activation of T cells (LAT) and infect Jurkat cells with it to establish stable cell line, and to investigate the effect of LAT palmitoylation mutation on T cell signaling induced by CD59. METHODS: Negative control (neg-EGFP) and LAT-M-EGFP fusion protein gene vectors were respectively constructed and then packaged using lentivirus. Subsequently, Jurkat cells were infected with them to establish stable cell lines...
August 2015: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Tomohiro Shinya, Tsubasa Yokota, Shiori Nakayama, Sayuri Oki, Junpei Mutoh, Satoru Takahashi, Keizo Sato
Angiogenesis, the formation of new blood vessels from pre-existing vessels, is essential for the growth and metastasis of tumors. In this study, we found that l-carbocisteine, a widely used expectorant, potently inhibits angiogenesis in vitro and in vivo. An in vivo Matrigel plug assay revealed that l-carbocisteine (2.5 mg/kg i.p. twice daily) significantly inhibited vascular endothelial growth factor (VEGF)-induced angiogenesis. l-Carbocisteine also suppressed VEGF-stimulated proliferation, migration, and formation of capillary-like structures of human umbilical vein endothelial cells (HUVECs)...
September 2015: Journal of Pharmacology and Experimental Therapeutics
Sarah A O'Brien, Minghua Zhu, Weiguo Zhang
Linker for activation of T cells (LAT) is a transmembrane adaptor protein that is highly tyrosine phosphorylated upon engagement of the TCR. Phosphorylated LAT binds Grb2, Gads, and phospholipase C (PLC)γ1 to mediate T cell activation, proliferation, and cytokine production. T cells from mice harboring a mutation at the PLCγ1 binding site of LAT (Y136F) have impaired calcium flux and Erk activation. Interestingly, these T cells are highly activated, resulting in the development of a lymphoproliferative syndrome in these mice...
July 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Hye-Jin Park, Hye Jeong Yang, Ki Hyun Kim, Sang Hee Kim
ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys japonicus A. Berger (Crassulaceae) (OJ), well-known as Wa-song in Korea is a medicinal plant with immunoregulatory, anti-febrile, antidote, and anti-cancer activities. This study was aimed at evaluating the immunostimulatory effect of O. japonicus A. Berger and its possible mechanisms of action. MATERIALS AND METHODS: To evaluate the effect of OJ aqueous extract on macrophage activity, we evaluated the modulation of macrophage activation state by observing structural (phagocytic activities) and the production of nitric oxide increase...
July 21, 2015: Journal of Ethnopharmacology
Po-Sheng Yang, Meng-Jiy Wang, Thanasekaran Jayakumar, Duen-Suey Chou, Ching-Ya Ko, Ming-Jen Hsu, Cheng-Ying Hsieh
Abnormal proliferation of vascular smooth muscle cells (VSMCs) is important in the pathogenesis of vascular disorders such as atherosclerosis and restenosis. Hinokitiol, a tropolone derivative found in Chamacyparis taiwanensis, has been found to exhibit anticancer activity in a variety of cancers through inhibition of cell proliferation. In the present study, the possible anti-proliferative effect of hinokitiol was investigated on VSMCs. Our results showed that hinokitiol significantly attenuated the PDGF-BB-stimulated proliferation of VSMCs without cytotoxicity...
May 7, 2015: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Teruhisa Takagishi, Masataka Oda, Michiko Kabura, Mie Kurosawa, Kaori Tominaga, Shiori Urano, Yoshibumi Ueda, Keiko Kobayashi, Toshihide Kobayashi, Jun Sakurai, Yutaka Terao, Masahiro Nagahama
Clostridium perfringens alpha-toxin elicits various immune responses such as the release of cytokines, chemokines, and superoxide via the GM1a/TrkA complex. Alpha-toxin possesses phospholipase C (PLC) hydrolytic activity that contributes to signal transduction in the pathogenesis of gas gangrene. Little is known about the relationship between lipid metabolism and TrkA activation by alpha-toxin. Using live-cell fluorescence microscopy, we monitored transbilayer movement of diacylglycerol (DAG) with the yellow fluorescent protein-tagged C1AB domain of protein kinase C-γ (EYFP-C1AB)...
2015: PloS One
Yongwei Zheng, Tamara Adams, Huiying Zhi, Mei Yu, Renren Wen, Peter J Newman, Demin Wang, Debra K Newman
Receptor-mediated platelet activation requires phospholipase C (PLC) activity to elevate intracellular calcium and induce actin cytoskeleton reorganization. PLCs are classified into structurally distinct β, γ, δ, ε, ζ, and η isoforms. There are two PLCγ isoforms (PLCγ1, PLCγ2), which are critical for activation by tyrosine kinase-dependent receptors. Platelets express both PLCγ1 and PLCγ2. Although PLCγ2 has been shown to play a dominant role in platelet activation, the extent to which PLCγ1 contributes has not been evaluated...
2015: PloS One
Jung Kuk Kim, Young-Kyo Seo, Sehoon Park, Soo-Ah Park, Seyoung Lim, Susie Lee, Ohman Kwon, Jeong Kon Seo, Ung-Kyu Choi, Sung Ho Ryu, Pann-Ghill Suh
Mast cells are responsible for IgE-mediated allergic responses through the secretion of various inflammatory cytokines and mediators. Therefore, the pharmacological regulation of mast cell activation is an important goal in the development of novel anti-allergic drugs. In this study, we found that spiraeoside (SP) inhibits mast cell activation and allergic responses in vivo. SP dose-dependently inhibited the degranulation induced by IgE-antigen (Ag) stimulation in RBL-2H3 mast cells without cytotoxic effects...
June 2015: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
Yi Chang, Wen-Hsien Hsu, Wan-Jung Lu, Thanasekaran Jayakumar, Jiun-Cheng Liao, Mei-Jiun Lin, Shwu-Huey Wang, Pitchairaj Geraldine, Kuan-Hung Lin, Joen-Rong Sheu
OBJECTIVE: CME-1 is a polysaccharide purified from the mycelia of medicinal mushroom Cordyceps sinensis, its molecular weight was determined to be 27.6 kDa by using nuclear magnetic resonance and gas chromatography-mass spectrometry. The initiation of arterial thromboses is relevant to various cardiovascular diseases (CVDs) and is believed to involve platelet activation. Our recent study exhibited that CME-1 has potent antiplatelet activity via the activation of adenylate cyclase/cyclic AMP ex vivo and in vivo...
2015: Current Pharmaceutical Biotechnology
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