Nuclear Phosphatidylinositol Signaling: Focus on Phosphatidylinositol Phosphate Kinases and Phospholipases C

Poli, Alessandro; Billi, Anna Maria; Mongiorgi, Sara; Ratti, Stefano; McCubrey, James A.; Suh, Pann Ghill; Cocco, Lucio; Ramazzotti, Giulia

doi:10.1002/jcp.25273

Cited by 41 publications

(40 citation statements)

References 139 publications

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“…The relative amounts of different phosphoinositide classes are changed in cells expressing mutant or transfected lipid phosphatases [5, 38]. Finally rapid changes of phosphoinositide signaling, inositol phosphate abundance, and membrane viscosity occur during the cell cycle perhaps through an increase of cells in G0/G1, and conversely, the cell cycle may be altered by phosphoinositides [44–49]. All these results emphasize that not only can the phosphorylation state of the inositol headgroup change in seconds during activity, but also the fatty-acid side chains can change at least within hours.…”

Section: Discussionmentioning

confidence: 99%

Fatty-acyl chain profiles of cellular phosphoinositides

Traynor‐Kaplan

Kruse

Dickson

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

120

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Phosphoinositides are rapidly turning-over phospholipids that play key roles in intracellular signaling and modulation of membrane effectors. Through technical refinements we have improved sensitivity in the analysis of the phosphoinositide PI, PIP, and PIP2 pools from living cells using mass spectrometry. This has permitted further resolution in phosphoinositide lipidomics from cell cultures and small samples of tissue. The technique includes butanol extraction, derivatization of the lipids, post-column infusion of sodium to stabilize formation of sodiated adducts, and electrospray ionization mass spectrometry in multiple reaction monitoring mode, achieving a detection limit of 20 pg. We describe the spectrum of fatty-acyl chains in the cellular phosphoinositides. Consistent with previous work in other mammalian primary cells, the 38:4 fatty-acyl chains dominate in the phosphoinositides of the pineal gland and of superior cervical ganglia, and many additional fatty acid combinations are found at low abundance. However, Chinese hamster ovary cells and human embryonic kidney cells (tsA201) in culture have different fatty-acyl chain profiles that change with growth state. Their 38:4 lipids lose their dominance as cultures approach confluence. The method has good time resolution and follows well the depletion in < 20 s of both PIP2 and PIP that results from strong activation of Gq-coupled receptors. The receptor-activated phospholipase C exhibits no substrate selectivity among the various fatty-acyl chain combinations.

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Section: Discussionmentioning

confidence: 99%

Fatty-acyl chain profiles of cellular phosphoinositides

Traynor‐Kaplan

Kruse

Dickson

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

120

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“…PLCs comprise of 6 sub-family members which hydrolyze PtdIns(4,5)P 2 to generate the two essential intracellular second messengers diacylglycerol (DAG) and inositol 1,4,5 trisphosphate (InsP 3 ) following their activation. This promotes the activation of protein kinase C (PKC) and the release of calcium ions (Ca 2+ ) from the intracellular stores, respectively [21][22][23][24]. InsP 3 detaches from the membrane and interacts with InsP 3 -specific receptors to regulate Ca 2+ release, while DAG remains membrane-bound to mediate the activation of PKC upon Ca 2+ release [25].…”

Section: Phospholipasesmentioning

confidence: 99%

Phosphoinositide-Dependent Signaling in Cancer: A Focus on Phospholipase C Isozymes

Obeng

Rusciano

Marvi

et al. 2020

IJMS

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Phosphoinositides (PI) form just a minor portion of the total phospholipid content in cells but are significantly involved in cancer development and progression. In several cancer types, phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] play significant roles in regulating survival, proliferation, invasion, and growth of cancer cells. Phosphoinositide-specific phospholipase C (PLC) catalyze the generation of the essential second messengers diacylglycerol (DAG) and inositol 1,4,5 trisphosphate (InsP3) by hydrolyzing PtdIns(4,5)P2. DAG and InsP3 regulate Protein Kinase C (PKC) activation and the release of calcium ions (Ca2+) into the cytosol, respectively. This event leads to the control of several important biological processes implicated in cancer. PLCs have been extensively studied in cancer but their regulatory roles in the oncogenic process are not fully understood. This review aims to provide up-to-date knowledge on the involvement of PLCs in cancer. We focus specifically on PLCβ, PLCγ, PLCδ, and PLCε isoforms due to the numerous evidence of their involvement in various cancer types.

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“…Notably, the above-mentioned decrease in PKC-a has been found in total lysates of the human K562 erythroleukemia cell line, but the behavior of PKC-a could change in nuclear and cytoplasmic fractions. Indeed, the cellular localization of the PI metabolism is extremely important because its enzymes may have different regulations and functions according to their localization (29)(30)(31)(32).…”

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confidence: 99%

Nuclear translocation of PKC‐ α is associated with cell cycle arrest and erythroid differentiation in myelodysplastic syndromes (MDSs)

et al. 2018

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PI-PLCβ1 is involved in cell proliferation, differentiation, and myelodysplastic syndrome (MDS) pathogenesis. Moreover, the increased activity of PI-PLCβ1 reduces the expression of PKC-α, which, in turn, delays the cell proliferation and is linked to erythropoiesis. Lenalidomide is currently used in low-risk patients with MDS and del(5q), where it can suppress the del(5q) clone and restore normal erythropoiesis. In this study, we analyzed the effect of lenalidomide on 16 patients with low-risk del(5q) MDS, as well as del(5q) and non-del(5q) hematopoietic cell lines, mainly focusing on erythropoiesis, cell cycle, and PI-PLCβ1/PKC-α signaling. Overall, 11 patients were evaluated clinically, and 10 (90%) had favorable responses; the remaining case had a stable disease. At a molecular level, both responder patients and del(5q) cells showed a specific induction of erythropoiesis, with a reduced γ/β-globin ratio, an increase in glycophorin A, and a nuclear translocation of PKC-α. Moreover, lenalidomide could induce a selective G/G arrest of the cell cycle in del(5q) cells, slowing down the rate proliferation in those cells. Altogether, our results could not only better explain the role of PI-PLCβ1/PKC-α signaling in erythropoiesis but also lead to a better comprehension of the lenalidomide effect on del(5q) MDS and pave the way to innovative, targeted therapies.-Poli, A., Ratti, S., Finelli, C., Mongiorgi, S., Clissa, C., Lonetti, A., Cappellini, A., Catozzi, A., Barraco, M., Suh, P.-G., Manzoli, L., McCubrey, J. A., Cocco, L., Follo, M. Y. Nuclear translocation of PKC-α is associated with cell cycle arrest and erythroid differentiation in myelodysplastic syndromes (MDSs).

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Nuclear Phosphatidylinositol Signaling: Focus on Phosphatidylinositol Phosphate Kinases and Phospholipases C

Cited by 41 publications

References 139 publications

Fatty-acyl chain profiles of cellular phosphoinositides

Fatty-acyl chain profiles of cellular phosphoinositides

Phosphoinositide-Dependent Signaling in Cancer: A Focus on Phospholipase C Isozymes

Nuclear translocation of PKC‐ α is associated with cell cycle arrest and erythroid differentiation in myelodysplastic syndromes (MDSs)

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