scholarly journals Cellular Localization and Functional Role of Phosphatidylcholine-Specific Phospholipase C in NK Cells

2001 ◽  
Vol 167 (5) ◽  
pp. 2642-2650 ◽  
Author(s):  
Carlo Ramoni ◽  
Francesca Spadaro ◽  
Michela Menegon ◽  
Franca Podo
Keyword(s):  
Nk Cells ◽  
Phospholipase C ◽  
Functional Role ◽  
Cellular Localization

Distribution, cellular localization and functional role of CCR2 chemokine receptors in adult rat brain

2002 ◽  
Vol 81 (2) ◽  
pp. 257-269 ◽  
Author(s):  
G. Banisadr ◽  
F. Quéraud-Lesaux ◽  
M. C. Boutterin ◽  
D. Pélaprat ◽  
B. Zalc ◽  
...  
Keyword(s):  
Rat Brain ◽  
Chemokine Receptors ◽  
Functional Role ◽  
Cellular Localization ◽  
Adult Rat ◽  
Adult Rat Brain

scholarly journals Multiphasic dynamics of phosphatidylinositol 4-phosphate during phagocytosis

2017 ◽  
Vol 28 (1) ◽  
pp. 128-140 ◽  
Author(s):  
Roni Levin ◽  
Gerald R. V. Hammond ◽  
Tamas Balla ◽  
Pietro De Camilli ◽  
Gregory D. Fairn ◽  
...  
Keyword(s):  
Phospholipase C ◽  
Functional Role ◽  
Hydrolytic Activity ◽  
Binding Domain ◽  
Target Particle ◽  
Phosphatidylinositol 4

We analyzed the distribution, fate, and functional role of phosphatidylinositol 4-phosphate (PtdIns4P) during phagosome formation and maturation. To this end, we used genetically encoded probes consisting of the PtdIns4P-binding domain of the bacterial effector SidM. PtdIns4P was found to undergo complex, multiphasic changes during phagocytosis. The phosphoinositide, which is present in the plasmalemma before engagement of the target particle, is transiently enriched in the phagosomal cup. Soon after the phagosome seals, PtdIns4P levels drop precipitously due to the hydrolytic activity of Sac2 and phospholipase C, becoming undetectable for ∼10 min. PtdIns4P disappearance coincides with the emergence of phagosomal PtdIns3P. Conversely, the disappearance of PtdIns3P that signals the transition from early to late phagosomes is accompanied by resurgence of PtdIns4P, which is associated with the recruitment of phosphatidylinositol 4-kinase 2A. The reacquisition of PtdIns4P can be prevented by silencing expression of the kinase and can be counteracted by recruitment of a 4-phosphatase with a heterodimerization system. Using these approaches, we found that the secondary accumulation of PtdIns4P is required for proper phagosomal acidification. Defective acidification may be caused by impaired recruitment of Rab7 effectors, including RILP, which were shown earlier to displace phagosomes toward perinuclear lysosomes. Our results show multimodal dynamics of PtdIns4P during phagocytosis and suggest that the phosphoinositide plays important roles during the maturation of the phagosome.

scholarly journals Stimulation of Fc gamma RIIIA results in phospholipase C-gamma 1 tyrosine phosphorylation and p56lck activation.

1992 ◽  
Vol 176 (6) ◽  
pp. 1745-1750 ◽  
Author(s):  
L Azzoni ◽  
M Kamoun ◽  
T W Salcedo ◽  
P Kanakaraj ◽  
B Perussia
Keyword(s):  
T Cells ◽  
Tyrosine Kinase ◽  
Nk Cells ◽  
Phospholipase C ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine ◽  
Tyrosine Residues ◽  
Stimulation Of

Binding of ligand to the alpha subunit of Fc gamma RIIIA(CD16), expressed at the natural killer (NK) cell membrane in association with homo or heterodimers of proteins of the zeta family, results in phosphorylation of several proteins on tyrosine residues. We have analyzed the role of protein tyrosine phosphorylation in the regulation of molecular events induced upon stimulation of Fc gamma RIIIA in NK cells and in T cells expressing the Fc gamma RIII alpha chain in association with endogenous zeta 2 homodimers and devoid of other (CD3, CD2) transducing molecules. Our data indicate that treatment of these cells with protein tyrosine kinase inhibitors prevents not only Fc gamma RIIIA-induced protein tyrosine phosphorylation but also phosphatidylinositol 4,5 diphosphate hydrolysis and increased intracellular Ca2+ concentration, indicating a primary role of tyrosine kinase(s) in the induction of these early activation events. Occupancy of Fc gamma RIIIA by ligand results in phospholipase C (PLC)-gamma 1 tyrosine phosphorylation in NK cells and in Fc gamma RIIIA-transfected CD3-/CD2- T cells, and induces functional activation of p56lck in Fc gamma RIIIA alpha/zeta 2-transfected T cells, suggesting the possibility that the receptor-induced PLC-gamma 1 activation occurs upon phosphorylation of its tyrosine residues mediated by this kinase and is, at least in part, responsible for the signal transduction mediated via CD16 upon ligand binding.

scholarly journals Functional role of phosphatidylcholine-specific phospholipase C in regulating CD16 membrane expression in natural killer cells

2007 ◽  
Vol 37 (10) ◽  
pp. 2912-2922 ◽  
Author(s):  
Serena Cecchetti ◽  
Francesca Spadaro ◽  
Luana Lugini ◽  
Franca Podo ◽  
Carlo Ramoni
Keyword(s):  
Natural Killer Cells ◽  
Natural Killer ◽  
Phospholipase C ◽  
Functional Role ◽  
Membrane Expression ◽  
Killer Cells

Characterization of CENPM Isoform Expression, Intracellular Localization, and Potential Functional Interactions In Mature B-Cell Malignancies

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2496-2496
Author(s):  
Kwok Min Hui ◽  
Xiaoyan Liu ◽  
Xin Feng ◽  
Anthony Brickner
Keyword(s):  
Amino Acid ◽  
B Cell ◽  
Cell Lines ◽  
Functional Role ◽  
Cellular Localization ◽  
Cell Lymphoma ◽  
Intracellular Localization ◽  
Lymphoid Malignancies ◽  
B Lymphoid

Abstract Abstract 2496 The lymphoid-specific PANE1 human minor histocompatibility antigen (mHAg) is overexpressed in primary chronic lymphocytic leukemia (CLL) cells. The PANE1 mHAg peptide is encoded by an alternative transcript of the centromere protein M (CENPM) gene, and may be a desirable target for immunotherapy due to its lymphoid specificity, and hence its potential to instigate a graft-versus-leukemia effect with absent or mitigated graft-versus-host disease. While its immunotherapeutic potential is compelling, little is presently known about the expression, cellular localization, and functional role of CENPM isoforms. To gain further insight into CENPM isoform expression and function in B-lymphoid and other malignancies, we assessed these characteristics of the CENPM transcript encoding a 58 amino acid isoform encompassing the mHAg (referred to as CENPM-S), and the longer canonical 180 amino acid CENPM isoform (referred to as CENPM-L). These two isoforms share a common 46 amino acid C-terminus, and differ in that the N-terminal 134 amino acids of CENPM-L are substituted in CENPM-S by a 12 amino acid sequence containing the mHAg peptide, which is derived from a novel exonization event within the fifth intron of the canonical genomic sequence. The CENPM-L isoform has been shown to be a critical component of the centromeric protein complex on which the transient assembly of the kinetochore occurs during mitosis. We determined that the novel CENPM-S mHAg-encoding exon and its adjacent predicted alternative promoter (distinct from that of CENPM-L) is derived from a LINE2 non-LTR retrotransposon insertion. To better assess the types of lymphoid malignancies that could potentially serve as targets of a CENPM-S-specific immune response, we examined a diverse panel of primary CLL cells, lymphoid malignancies and lymphoma cell lines for the expression of CENPM-S and CENPM-L via quantitative real-time PCR (qRT-PCR). In accord with our previous results, highest levels of CENPM-S were observed in primary CLL cells. Within lymphoma cell lines, moderate levels of CENPM-S were seen in mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) cells, and expression was detectable in only one out of four multiple myeloma cell lines surveyed. Within a panel of human lymphoma tumor samples, highest levels of CENPM-S were observed in marginal zone lymphoma, DLBCL, MCL, follicular lymphoma, and one peripheral T-cell lymphoma sample. Strikingly, the highest levels of CENPM-S and the lowest levels of CENPM-L were always observed specifically in primary CLL cells, and such high ratios of CENPM-S to CENPM-L expression were not observed in any other B-cell malignancy surveyed. These results suggest a profound transcriptional switch from the upstream canonical promoter to the putative LINE2 element-proximal CENPM-S alternative promoter, which occurs exclusively in CLL cells. In order to further elucidate the cellular localization and potential function of the CENPM-S and CENPM-L isoforms, we transiently transfected vectors encoding FLAG-tagged CENPM isoforms in HeLa cells. Transfected cells were subjected to subcellular fractionation followed by Western blot with anti-FLAG antibodies, which indicated CENPM-L localization to cytoplasmic, membrane, soluble nuclear, and cytoskeletal fractions, in accord with our observations of endogenous CENPM-L in Granta-519 MCL cells using CENPM-L-specific monoclonal antibody. In contrast, CENPM-S exhibited localization in cytoplasm and membrane and was present only weakly in the soluble nuclear fraction. Preliminary immunofluorescence microscopy data are in agreement with these patterns of intracellular localization. We are presently assessing CENPM isoforms for impact on cell cycle, proliferation, and apoptosis, in order to better understand their potential involvement in biological processes underlying CLL and other non-Hodgkins lymphomas. To further elucidate the potential functional role of CENPM-S in mature B-lymphocytes and mature B-lymphoid malignancies, we performed yeast two-hybrid library screening with a human bone marrow cDNA library to reveal putative interacting proteins. The non-muscle myosin protein, myosin IIA, was revealed as a strong candidate CENPM-S interacting protein. We have recently validated via sandwich ELISA an interaction between endogenous myosin IIA (within Granta-519 MCL cell extract) and recombinant CENPM-S. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Expression and Functional Role of α7 Nicotinic Receptor in Human Cytokine-stimulated Natural Killer (NK) Cells

2016 ◽  
Vol 291 (32) ◽  
pp. 16541-16552 ◽  
Author(s):  
Samanta R. Zanetti ◽  
Andrea Ziblat ◽  
Nicolás I. Torres ◽  
Norberto W. Zwirner ◽  
Cecilia Bouzat
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nicotinic Receptor ◽  
Functional Role ◽  
Human Cytokine
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