References of "Erneux, Christophe"
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See detailSpecific expression and function of inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) in wild type and knock-out mice
Scoumanne, Ariane; Molina Ortiz, Patricia ULg; Monteyne, Daniel et al

in Advances in Biological Regulation (in press)

Inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) is the last identified member of the inositol 1,4,5-trisphosphate 3-kinases family which phosphorylates inositol 1,4,5-trisphosphate into inositol 1,3,4,5 ... [more ▼]

Inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) is the last identified member of the inositol 1,4,5-trisphosphate 3-kinases family which phosphorylates inositol 1,4,5-trisphosphate into inositol 1,3,4,5-tetrakisphosphate. Although expression and function of the two other family members ITPKA and ITPKB are rather well characterized, similar information is lacking for ITPKC. Here, we first defined the expression of Itpkc mRNA and protein in mouse tissues and cells using in situ hybridization and new antibodies. Surprisingly, we found that cells positive for ITPKC in the studied tissues express either a multicilium (tracheal and bronchial epithelia, brain ependymal cells), microvilli forming a brush border (small and large intestine, and kidney proximal tubule cells) or a flagellum (spermatozoa), suggesting a role for ITPKC either in the development or the function of these specialized cellular structures. Given this surprising expression, we then analyzed ITPKC function in multiciliated tracheal epithelial cells and sperm cells using our Itpkc knock-out mouse model. Unfortunately, no significant difference was observed between control and mutant mice for any of the parameters tested, leaving the exact in vivo function of this third Ins(1,4,5)P3 3-kinase still open. [less ▲]

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See detailSHIP2 controls plasma membrane PI(4,5)P2 thereby participating in the control of cell migration in 1321 N1 glioblastoma.
Edimo, William S Elong; Ghosh, Somadri; Derua, Rita et al

in Journal of cell science (2016)

Phosphoinositides, particularly PI(3,4,5)P3, and PI(4,5)P2, are recognized by SHIP2 a member of the inositol polyphosphate 5-phosphatase family. SHIP2 dephosphorylates PI(3,4,5)P3 to form PI(3,4)P2; the ... [more ▼]

Phosphoinositides, particularly PI(3,4,5)P3, and PI(4,5)P2, are recognized by SHIP2 a member of the inositol polyphosphate 5-phosphatase family. SHIP2 dephosphorylates PI(3,4,5)P3 to form PI(3,4)P2; the latter interacts with specific target proteins (e.g. lamellipodin). Although the SHIP2 preferred substrate is PI(3,4,5)P3, PI(4,5)P2 could also be dephosphorylated to PI4P. Through depletion of SHIP2 in a glioblastoma cell line 1321 N1 cells, we show that SHIP2 inhibits cell migration. In different glioblastoma cell lines and primary cultures, SHIP2 staining at the plasma membrane partly overlaps with PI(4,5)P2 immunoreactivity. PI(4,5)P2 was upregulated in SHIP2-deficient N1 cells as compared to control cells; in contrast, PI4P was very much decreased in SHIP2-deficient cells. Therefore, SHIP2 controls both PI(3,4,5)P3 and PI(4,5)P2 levels in intact cells. In N1 cells, the PI(4,5)P2 binding protein myosin-1c was identified as a new interactor of SHIP2. Regulation of PI(4,5)P2 and PI4P content by SHIP2 controls N1 cell migration through the organization of focal adhesions. Thus, our results reveal a novel role of SHIP2 in the control of PI(4,5)P2, PI4P and cell migration in PTEN-deficient glioblastoma N1 cells. [less ▲]

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See detailInositol 1,4,5-trisphosphate 3-kinase B (Itpkb) controls survival, proliferation and cytokine production in mouse peripheral T cells
Pouillon, Valérie; Maréchal, Yoann; Frippiat, Christophe et al

in Advances in Biological Regulation (2013), 53(1), 39-50

Mice genetically-deficient for the B isoform of the inositol 1,4,5-trisphosphate 3-kinase (or Itpkb) have a severe defect in thymocytes differentiation and thus lack peripheral T cells. In order to study ... [more ▼]

Mice genetically-deficient for the B isoform of the inositol 1,4,5-trisphosphate 3-kinase (or Itpkb) have a severe defect in thymocytes differentiation and thus lack peripheral T cells. In order to study the functional role of Itpkb in peripheral T cells, we constructed a new mouse where a transgene encoding mouse Itpkb is specifically and transiently expressed in thymocytes of Itpkb-/- mice. This allows a partial rescue of mature thymocyte/T cell differentiation and thus the functional characterization of peripheral T cells lacking Itpkb. We show here that Itpkb-/- CD4+ and CD8+ peripheral T cells present important functional alterations. Indeed, an increased activated/memory phenotype as well as a decreased proliferative capacity and survival were detected in these T cells. These Itpkb-deficient peripheral T cells have also an increased capacity to secrete cytokines upon stimulation. Together, our present results define the important role of Itpkb in peripheral mature T cell fate and function in mouse, suggesting a potential role for Itpkb in autoimmunity. [less ▲]

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See detailSHIP-1 inhibits CD95/APO-1/Fas-induced apoptosis in primary T lymphocytes and T leukemic cells by promoting CD95 glycosylation independently of its phosphatase activity
Charlier, Edith ULg; Condé, Claude ULg; Zhang, Jing et al

in Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K (2010)

SHIP-1 functions as a negative regulator of immune responses by hydrolyzing phosphatidylinositol-3,4,5-triphosphate generated by PI 3-kinase activity. As a result, SHIP-1 deficiency in mice results in ... [more ▼]

SHIP-1 functions as a negative regulator of immune responses by hydrolyzing phosphatidylinositol-3,4,5-triphosphate generated by PI 3-kinase activity. As a result, SHIP-1 deficiency in mice results in myeloproliferation and B cell lymphoma. On the other hand, SHIP-1 deficient mice have a reduced T cell population, but the underlying mechanisms are unknown. In this work, we hypothesized that SHIP-1 plays anti-apoptotic functions in T cells upon stimulation of the death receptor CD95/APO-1/Fas. Using primary T cells from SHIP-1-/- mice and T leukemic cell lines, we report here that SHIP-1 is a potent inhibitor of CD95-induced death. We observed that a small fraction of the SHIP-1 pool is localized to the endoplasmic reticulum where it promotes CD95 glycosylation. This post-translational modification requires an intact SH2 domain of SHIP-1, but is independent of its phosphatase activity. The glycosylated CD95 fails to oligomerize upon stimulation, resulting in impaired DISC formation and downstream apoptotic cascade. These results uncover an unanticipated inhibitory function for SHIP-1 and emphasize the role of glycosylation in the regulation of CD95 signaling in T cells. This work may also provide a new basis for therapeutic strategies using compounds inducing apoptosis through the CD95 pathway on SHIP-1 negative leukemic T cells. [less ▲]

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See detailThe role of SHIP1 in T-lymphocyte life and death
Gloire, Geoffrey ULg; Erneux, Christophe; Piette, Jacques ULg

in Biochemical Society Transactions (2007), 35(Pt 2), 277-280

SHIP1 [SH2 (Src homology 2)-containing inositol phosphatase-1], an inositol 5-phosphatase expressed in haemopoietic cells, acts by hydrolysing the 5-phosphates from PtdIns(3,4,5)P(3) and Ins(1,3,4,5)P(4 ... [more ▼]

SHIP1 [SH2 (Src homology 2)-containing inositol phosphatase-1], an inositol 5-phosphatase expressed in haemopoietic cells, acts by hydrolysing the 5-phosphates from PtdIns(3,4,5)P(3) and Ins(1,3,4,5)P(4), thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathway. SHIP1 plays a major role in inhibiting proliferation of myeloid cells. As a result, SHIP1(-/-) mice have an increased number of neutrophils and monocytes/macrophages due to enhanced survival and proliferation of their progenitors. Although SHIP1 contributes to PtdIns(3,4,5)P(3) metabolism in T-lymphocytes, its exact role in this cell type is much less explored. Jurkat cells have recently emerged as an interesting tool to study SHIP1 function in T-cells because they do not express SHIP1 at the protein level, thereby allowing reintroduction experiments in a relatively easy-to-use system. Data obtained from SHIP1 reintroduction have revealed that SHIP1 not only acts as a negative player in T-cell lines proliferation, but also regulates critical pathways, such as NF-kappaB (nuclear factor kappaB) activation, and also appears to remarkably inhibit T-cell apoptosis. On the other hand, experiments using primary T-cells from SHIP1(-/-) mice have highlighted a new role for SHIP1 in regulatory T-cell development, but also emphasize that this protein is not required for T-cell proliferation. In support of these results, SHIP1(-/-) mice are lymphopenic, suggesting that SHIP1 function in T-cells differs from its role in the myeloid lineage. [less ▲]

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See detailRestoration of SHIP-1 activity in human leukemic cells modifies NF-kappaB activation pathway and cellular survival upon oxidative stress.
Gloire, Geoffrey ULg; Charlier, Edith ULg; Rahmouni, Souad ULg et al

in Oncogene (2006), 25(40), 5485-94

Nuclear factor-kappa B (NF-kappaB) is an important prosurvival transcription factor activated in response to a large array of external stimuli, including reactive oxygen species (ROS). Previous works have ... [more ▼]

Nuclear factor-kappa B (NF-kappaB) is an important prosurvival transcription factor activated in response to a large array of external stimuli, including reactive oxygen species (ROS). Previous works have shown that NF-kappaB activation by ROS involved tyrosine phosphorylation of the inhibitor IkappaBalpha through an IkappaB kinase (IKK)-independent mechanism. In the present work, we investigated with more details NF-kappaB redox regulation in human leukemic cells. By using different cell lines (CEM, Jurkat and the subclone Jurkat JR), we clearly showed that NF-kappaB activation by hydrogen peroxide (H2O2) is cell-type dependent: it activates NF-kappaB through tyrosine phosphorylation of IkappaBalpha in Jurkat cells, whereas it induces an IKK-mediated IkappaBalpha phosphorylation on S32 and 36 in CEM and Jurkat JR cells. We showed that this H2O2-induced IKK activation in CEM and Jurkat JR cells is mediated by SH2-containing inositol 5'-phosphatase 1 (SHIP-1), a lipid phosphatase that is absent in Jurkat cells. Indeed, the complementation of SHIP-1 in Jurkat cells made them shift to an IKK-dependent mechanism upon oxidative stress stimulation. We also showed that Jurkat cells expressing SHIP-1 are more resistant to H2O2-induced apoptosis than the parental cells, suggesting that SHIP-1 has an important role in leukemic cell responses to ROS in terms of signal transduction pathways and apoptosis resistance, which can be of interest in improving ROS-mediated chemotherapies. [less ▲]

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See detailIdentification and subcellular distribution of endogenous Ins(1,4,5)P3 3-kinase B in mouse tissues
Hascakova-Bartova, Romana; Pouillon, Valérie; Dewaste, Valérie et al

in Biochemical and Biophysical Research Communications (2004), 323(3), 920-925

Inositol 1,4,5-trisphosphate 3-kinase (IP3-3K) catalyses the phosphorylation of inositol 1,4,5-trisphosphate to inositol 1,3,4,5-tetrakisphosphate. cDNAs encoding three mammalian isoforms have been ... [more ▼]

Inositol 1,4,5-trisphosphate 3-kinase (IP3-3K) catalyses the phosphorylation of inositol 1,4,5-trisphosphate to inositol 1,3,4,5-tetrakisphosphate. cDNAs encoding three mammalian isoforms have been reported and referred to as IP3-3KA, IP3-3KB, and IP3-3KC. IP3-3KB is particularly sensitive to proteolysis at the N-terminus, a mechanism known to generate active fragments of lower molecular mass. Endogenous IP3-3KB has therefore not been formally identified in tissues. We have probed a series of murine tissues with an antibody directed against the C-terminus of IP3-3KB and used IP3-3KB deficient mouse tissues as negative controls. IP3-3KB was shown to be particularly well expressed in brain, lung, and thymus with molecular masses of 110–120 kDa. The identification of the native IP3-3KB by Western blotting for the first time will facilitate further studies of regulation of its activity by specific proteases and/or phosphorylation [less ▲]

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See detailThe SH2 domain containing 5-phosphatase SHIP2 is expressed in the germinal layers of embryo and adult mouse brain : increased expression in N_CAM deficient mice.
Muraille, Eric; Dassesse, Donald; Vanderwinden, Jean-Marie et al

in Neuroscience (2001), 105

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