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PLC delta

Istvan Borbiro, Doreen Badheka, Tibor Rohacs
Capsaicin is an activator of the heat-sensitive TRPV1 (transient receptor potential vanilloid 1) ion channels and has been used as a local analgesic. We found that activation of TRPV1 channels with capsaicin either in dorsal root ganglion neurons or in a heterologous expression system inhibited the mechanosensitive Piezo1 and Piezo2 channels by depleting phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and its precursor phosphatidylinositol 4-phosphate [PI(4)P] from the plasma membrane through Ca(2+)-induced phospholipase Cδ (PLCδ) activation...
February 10, 2015: Science Signaling
Gustavo de Rezende Corrêa, Vinicius Henrique Pedrosa Soares, Leandro de Araújo-Martins, Aline Araujo Dos Santos, Elizabeth Giestal-de-Araujo
Brain-derived neurotrophic factor (BDNF) is a well-known and well-studied neurotrophin. Most biological effects of BDNF are mediated by the activation of TrkB receptors. This neurotrophin regulates several neuronal functions as cell proliferation, viability, and differentiation. Ouabain is a steroid that binds to the Na(+)/K(+) ATPase, inducing the activation of several intracellular signaling pathways. Previous data from our group described that ouabain treatment increases retinal ganglion cells survival (RGC)...
July 2015: Cellular and Molecular Neurobiology
Laura Vachel, Caroline Norez, Christophe Jayle, Frédéric Becq, Clarisse Vandebrouck
Increase of Ca(2+) influx in Cystic Fibrosis (CF) cells has been reported to be related to Transient Receptor Potential Canonical (TRPC6) channel, which is implicated in a functional coupling with Cystic Fibrosis Transmembrane conductance Regulator (CFTR). Several members of the Transient Receptor Potential Vanilloid (TRPV) channels family have already been described as emerging target for respiratory diseases. Two specific isoforms, TRPV5 and TRPV6 are of particular interest in the context of CF Ca(2+) homeostasis as they are highly selective toward Ca(2+) and constitutively activated...
January 2015: Cell Calcium
Reiko Satow, Tamaki Hirano, Ryosuke Batori, Tomomi Nakamura, Yumi Murayama, Kiyoko Fukami
Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths worldwide, and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in CRC predict the ineffectiveness of EGF receptor-targeted therapy. Previous transcriptional microarray analysis suggests the association between phospholipase Cδ1 (PLCδ1) expression and KRAS mutation status in CRC. However, both the roles and the regulatory mechanisms of PLCδ1 in CRC are not known. Here, we found that the expression of PLCδ1, one of the most basal PLCs, is down-regulated in CRC specimens compared with normal colon epithelium by immunohistochemistry...
September 16, 2014: Proceedings of the National Academy of Sciences of the United States of America
Emilie Decaup, Caroline Duault, Christine Bezombes, Mary Poupot, Ariel Savina, Daniel Olive, Jean-Jacques Fournié
Human γδ cells expressing TCRVγ9 are T lymphocytes with great potential for cancer immunotherapy and unconventional pattern of antigen specificity. These HLA-unrestricted lymphocytes are specifically reactive to non-peptide metabolites (phosphoantigens) and to the butyrophilin 3A (BTN3A/CD277) protein. Whether recognition of such highly different structures trigger the same activation signaling pathway remains unclear, however. Here we combined fluorescent cell barcoding and phosphoflow analysis of TCRVγ9(+) T lymphocytes to compare simultaneously the level of several signaling phosphoproteins after activation by phosphoantigen (BrHPP) or by anti-BTN3A (monoclonal antibody 20...
September 2014: Immunology Letters
V R Lo Vasco, M Leopizzi, C Puggioni, C Della Rocca, R Businaro
Endothelial cells (EC) are the first elements exposed to mediators circulating in the bloodstream, and react to stimulation with finely tuned responses mediated by different signal transduction pathways, leading the endothelium to adapt. Neuropeptide Y (NPY), the most abundant peptide in heart and brain, is mainly involved in the neuroendocrine regulation of the stress response. The regulatory roles of NPY depend on many factors, including its enzymatic processing, receptor subtypes and related signal transduction systems, including the phosphoinositide (PI) pathway and related phospholipase C (PI-PLC) family of enzymes...
September 2014: Molecular and Cellular Biochemistry
Y Nakamura, K Kanemaru, R Kojima, Y Hashimoto, T Marunouchi, N Oka, T Ogura, K Tanonaka, K Fukami
Phospholipase C (PLC) is a key enzyme in phosphoinositide turnover. Among 13 PLC isozymes, PLCδ1 and PLCδ3 share high sequence homology and similar tissue distribution, and are expected to have functional redundancy in many tissues. We previously reported that the simultaneous loss of PLCδ1 and PLCδ3 caused embryonic lethality because of excessive apoptosis and impaired vascularization of the placenta. Prenatal death of PLCδ1/PLCδ3 double-knockout mice hampered our investigation of the roles of these genes in adult animals...
2014: Cell Death & Disease
Boyoung Cha, Tiane Chen, Rafiquel Sarker, Jianbo Yang, Daniel Raben, C Ming Tse, Olga Kovbasnjuk, Mark Donowitz
The Na(+)/H(+) exchanger 3 (NHE3) is a brush border (BB) Na(+)/H(+) antiporter that accounts for the majority of physiologic small intestinal and renal Na(+) absorption. It is regulated physiologically and in disease via changes in endocytosis/exocytosis. Paradoxically, NHE3 is fixed to the microvillar (MV) actin cytoskeleton and has little basal mobility. This fixation requires NHE3 binding to the multi-PDZ domain scaffold proteins Na(+)/H(+) exchanger regulatory factor (NHERF)1 and NHERF2 and to ezrin. Coordinated release of NHE3 from the MV cytoskeleton has been demonstrated during both stimulation and inhibition of NHE3...
July 1, 2014: American Journal of Physiology. Cell Physiology
Xin Hui, Gregor Reither, Lars Kaestner, Peter Lipp
Activation of the two ubiquitous families of protein kinases, protein kinase A (PKA) and protein kinase C (PKC), is thought to be independently coupled to stimulation of Gαs and Gαq, respectively. Live-cell confocal imaging of protein kinase C fluorescent protein fusion constructs revealed that simultaneous activation of Gαs and Gαq resulted in a differential translocation of the conventional PKCα to the plasma membrane while the novel PKCδ was recruited to the membrane of the endoplasmic reticulum (ER)...
July 2014: Molecular and Cellular Biology
Natalia Freitas, Celso Cunha, Stephan Menne, Severin O Gudima
UNLABELLED: A natural subviral agent of human hepatitis B virus (HBV), hepatitis delta virus (HDV), requires only the envelope proteins from HBV in order to maintain persistent infection. HBV surface antigens (HBsAgs) can be produced either by HBV replication or from integrated HBV DNA regardless of replication. The functional properties of the integrant-generated HBsAgs were examined using two human hepatocellular carcinoma-derived cell lines, Hep3B and PLC/PRF/5, that contain HBV integrants but do not produce HBV virions and have no signs of HBV replication...
May 2014: Journal of Virology
Jiean Huang, Ancy D Nalli, Sunila Mahavadi, Divya P Kumar, Karnam S Murthy
Others and we have characterized several Gβγ-dependent effectors in smooth muscle, including G protein-coupled receptor kinase 2 (GRK2), PLCβ3, and phosphatidylinositol (PI) 3-kinase-γ, and have identified various signaling targets downstream of PI 3-kinase-γ, including cSrc, integrin-linked kinase, and Rac1-Cdc42/p21-activated kinase/p38 MAP kinase. This study identified a novel mechanism whereby Gβγ acting via PI 3-kinase-γ and cSrc exerts an inhibitory influence on Gαi activity. The Gi2-coupled δ-opioid receptor agonist d-penicillamine (2,5)-enkephalin (DPDPE) activated cSrc, stimulated tyrosine phosphorylation of Gαi2, and induced regulator of G protein signaling 12 (RGS12) association; all three events were blocked by PI 3-kinase (LY294002) and cSrc (PP2) inhibitors and by expression of the COOH-terminal sequence of GRK2-(495-689), a Gβγ-scavenging peptide...
May 1, 2014: American Journal of Physiology. Gastrointestinal and Liver Physiology
Sarah A Sullivan, Minghua Zhu, Steven Bao, Catherine A Lewis, Chih-wen Ou-Yang, Weiguo Zhang
LAT is a transmembrane adaptor protein that is vital for integrating TCR-mediated signals to modulate T cell development, activation, and proliferation. Upon T cell activation, LAT is phosphorylated and associates with Grb2, Gads, and PLCγ1 through its four distal tyrosine residues. Mutation of one of these tyrosines, Y136, abolishes LAT binding to PLCγ1. This results in impaired TCR-mediated calcium mobilization and Erk activation. CD4 αβ T cells in LATY136F knock-in mice undergo uncontrolled expansion, resulting in a severe autoimmune syndrome...
March 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Vincenza Rita Lo Vasco, Martina Leopizzi, Chiara Puggioni, Carlo Della Rocca, Rita Businaro
Besides the control of calcium levels, the phosphoinositide-specific phospholipases C (PI-PLCs), the main players in the phosphoinositide signalling pathway, contribute to a number of cell activities. The expression of PI-PLCs is strictly tissue specific and evidence suggests that it varies under different conditions, such as tumour progression or cell activation. In previous studies, we obtained a complete panel of expression of PI-PLC isoforms in human umbilical vein endothelial cells (HUVEC), a widely used experimental model for endothelial cells (EC), and demonstrated that the expression of the PLC genes varies under inflammatory stimulation...
March 2014: Molecular and Cellular Biochemistry
Jingfei Cai, Su Guo, Jon W Lomasney, Mary F Roberts
Recombinant EF-hand domain of phospholipase C δ1 has a moderate affinity for anionic phospholipids in the absence of Ca(2+) that is driven by interactions of cationic and hydrophobic residues in the first EF-hand sequence. This region of PLC δ1 is missing in the crystal structure. The relative orientation of recombinant EF with respect to the bilayer, established with NMR methods, shows that the N-terminal helix of EF-1 is close to the membrane interface. Specific mutations of EF-1 residues in full-length PLC δ1 reduce enzyme activity but not because of disturbing partitioning of the protein onto vesicles...
December 27, 2013: Journal of Biological Chemistry
Joshua Jamison, Douglas Lauffenburger, James C-H Wang, Alan Wells
INTRODUCTION: During wound healing, fibroblasts initially migrate into the wound bed and later contract the matrix. Relevant mediators of transcellular contractility revealed by systems analyses are protein kinase c delta/myosin light chain-2 (PKCδ/MLC-2). PKCδ is activated by growth factor-driven PLCγ1 hydrolysis of phosphoinositide bisphosphate (PIP2) hydrolysis when it becomes tranlocated to the membrane. This leads to MLC-2 phosphorylation that regulates myosin for contractility...
2013: PloS One
Na Young Kim, Sang Jung Ahn, Moo-Sang Kim, Jung Soo Seo, Se Hwan Jung, Sung Hwan Park, Hyung Ho Lee, Joon Ki Chung
Mud loach phospholipase C-δ1 (MlPLC-δ1) contains all the characteristic domains found in mammalian PLC-δ isozymes (pleckstrin homology domain, EF-hands, X–Y catalytic region, and C2 domain) as well as an extended 26-amino acid (aa)-long N-terminal region that is an alternative splice form of PLC-δ1 and is novel to vertebrate PLC-δ. In the present structure-function analysis, deletion of the extended N-terminal region caused complete loss of phosphatidylinositol (PI)- and phosphatidylinositol 4,5-bisphosphate (PIP2)-hydrolyzing activity in MlPLC-δ1...
January 2014: Applied Biochemistry and Biotechnology
Hye Jin Bak, Moo-Sang Kim, Na Young Kim, A Ram Lee, Ju Hyeon Park, Jin Young Lee, Bo Seong Kim, Sang Jung Ahn, Hyung Ho Lee, Joon Ki Chung
Phospholipase Cδ4 (PLCδ4) plays a significant role in cell proliferation, tumorigenesis, and in an early stage of fertilization. Despite the characterization of the mammalian PLCδ4, extensive study in aquatic organisms has not been carried out so far. Here, we performed the molecular and biochemical characterization of flatfish Paralichthys olivaceus PLCδ4 (PoPLCδ4) to understand its enzymatic properties and physiological functions. The olive flounder PLCδ4 cDNA has an open reading frame (ORF) of 2,268 bp, and encodes a 755 amino acid polypeptide with a predicted molecular weight of 86 kDa...
November 2013: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
Kim A Staats, Lawrence Van Helleputte, Ashley R Jones, André Bento-Abreu, Annelies Van Hoecke, Aleksey Shatunov, Claire L Simpson, Robin Lemmens, Tom Jaspers, Kiyoko Fukami, Yoshikazu Nakamura, Robert H Brown, Philip Van Damme, Adrian Liston, Wim Robberecht, Ammar Al-Chalabi, Ludo Van Den Bosch
Amyotrophic Lateral Sclerosis (ALS) is a devastating progressive neurodegenerative disease, resulting in selective motor neuron degeneration and paralysis. Patients die approximately 3-5 years after diagnosis. Disease pathophysiology is multifactorial, including excitotoxicity, but is not yet fully understood. Genetic analysis has proven fruitful in the past to further understand genes modulating the disease and increase knowledge of disease mechanisms. Here, we revisit a previously performed microsatellite analysis in ALS and focus on another hit, PLCD1, encoding phospholipase C delta 1 (PLCδ1), to investigate its role in ALS...
December 2013: Neurobiology of Disease
Yoshikazu Nakamura, Kaori Kanemarum, Kiyoko Fukami
Phospholipase C (PLC) is a key enzyme in phosphoinositide turnover, and in the regulation of various cellular events. Among the 13 PLC isozymes, PLCδ1 and PLCδ3 share a high sequence homology, and similar tissue distribution. Recent studies with genetically manipulated mice have clarified the importance of these PLC isozymes in a number of tissues. PLCδ1 is required for maintenance of homeostasis in skin and metabolic tissues, while PLCδ3 regulates microvilli formation in enterocytes and the radial migration of neurons in the cerebral cortex of the developing brain...
September 2013: Advances in Biological Regulation
Shanshan Yin, Jianmin Zhang, Yujia Mao, Yu Hu, Lianxian Cui, Ning Kang, Wei He
T cell antigen receptor γδ (TCRγδ) and natural killer group 2, member D (NKG2D) are two crucial receptors for γδT cell cytotoxicity. Compelling evidences suggest that γδT cell cytotoxicity is TCRγδ-dependent and can be co-stimulated by NKG2D. However, the molecular mechanism of underlying TCRγδ-dependent activation of γδT cells remains unclear. In this study we demonstrated that TCRγδ but not NKG2D engagement induced lytic granule polarization and promoted γδT cell cytotoxicity. TCRγδ activation alone was sufficient to trigger Vav1-dependent phospholipase C-γ1 signaling, resulting in lytic granule polarization and effective killing, whereas NKG2D engagement alone failed to trigger cytotoxicity-related signaling to overcome the inhibitory effect of Cbl-b; therefore, NKG2D engagement alone could not induce effective killing...
September 13, 2013: Journal of Biological Chemistry
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