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PLC delta

Stefania Gessi, Serena Bencivenni, Enrica Battistello, Fabrizio Vincenzi, Vittoria Colotta, Daniela Catarzi, Flavia Varano, Stefania Merighi, Pier Andrea Borea, Katia Varani
Several evidences indicate that the ubiquitous nucleoside adenosine, acting through A1 , A2A , A2B , and A3 receptor (AR) subtypes, plays crucial roles in tumor development. Adenosine has contrasting effects on cell proliferation depending on the engagement of different receptor subtypes in various tumors. The involvement of A2A ARs in human A375 melanoma, as well as in human A549 lung and rat MRMT1 breast carcinoma proliferation has been evaluated in view of the availability of a novel A2A AR antagonist, with high affinity and selectivity, named as 2-(2-furanyl)-N5 -(2-methoxybenzyl)[1,3]thiazolo[5,4-d]pyrimidine-5,7-diammine (TP455)...
2017: Frontiers in Pharmacology
Lu-Kang Wang, Xin Chen, Chun-Qing Zhang, Chao Liang, Yu-Jia Wei, Jiong Yue, Shi-Yong Liu, Hui Yang
Focal cortical dysplasia type II (FCD II) and tuberous sclerosis complex (TSC) are well-known causes of chronic refractory epilepsy in children. Canonical transient receptor potential channels (TRPCs) are non-selective cation channels that are commonly activated by phospholipase C (PLC) stimulation. Previous studies found that TRPC4 may participate in the process of epileptogenesis. This study aimed to examine the expression and distribution of TRPC4 in FCD II (n = 24) and TSC (n = 11) surgical specimens compared with that in age-matched autopsy control samples (n = 12)...
June 2017: Journal of Molecular Neuroscience: MN
Eva Bilkova, Roman Pleskot, Sami Rissanen, Simou Sun, Aleksander Czogalla, Lukasz Cwiklik, Tomasz Róg, Ilpo Vattulainen, Paul S Cremer, Pavel Jungwirth, Ünal Coskun
The orchestrated recognition of phosphoinositides and concomitant intracellular release of Ca(2+) is pivotal to almost every aspect of cellular processes, including membrane homeostasis, cell division and growth, vesicle trafficking, as well as secretion. Although Ca(2+) is known to directly impact phosphoinositide clustering, little is known about the molecular basis for this or its significance in cellular signaling. Here, we study the direct interaction of Ca(2+) with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), the main lipid marker of the plasma membrane...
March 22, 2017: Journal of the American Chemical Society
Stefania Merighi, Serena Bencivenni, Fabrizio Vincenzi, Katia Varani, Pier Andrea Borea, Stefania Gessi
The hallmark of neuroinflammation is the activation of microglia, the immunocompetent cells of the CNS, releasing a number of proinflammatory mediators implicated in the pathogenesis of neuronal diseases. Adenosine is an ubiquitous autacoid regulating several microglia functions through four receptor subtypes named A1 , A2A , A2B and A3 (ARs), that represent good targets to suppress inflammation occurring in CNS. Here we investigated the potential role of ARs in the modulation of IL-6 secretion and cell proliferation in primary microglial cells...
March 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Michail Nomikos, Angelos Thanassoulas, Konrad Beck, Maria Theodoridou, Jasmine Kew, Junaid Kashir, Brian L Calver, Emily Matthews, Pierre Rizkallah, Zili Sideratou, George Nounesis, F Anthony Lai
Hereditary leukonychia is a rare genetic nail disorder characterized by distinctive whitening of the nail plate of all 20 nails. Hereditary leukonychia may exist as an isolated feature, or in simultaneous occurrence with other cutaneous or systemic pathologies. Associations between hereditary leukonychia and mutations in the gene encoding phospholipase C delta-1 (PLCδ1) have previously been identified. However, the molecular mechanisms underlying PLCδ1 mutations and hereditary leukonychia remain uncharacterized...
December 2016: FEBS Journal
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
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