Nuclear phosphoinositidase C during growth factor stimulation (original) (raw)
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FEBS Letters, 1994
Beside 4-and S-phosphatases playing a role in the interconversion between the D-3 phosphorylated polyphosphoinositides, the only enzyme described so far to be responsible for a phosphomonoesterasic activity on the D-3 position of inositol lipids is a specific 3-phosphatase that hydrolyzes PtdIns(3)P in NIH 3T3 cells. We report here the presence of a potent 3-phosphatase activity in different cell types. This activity is detected both in cytosol and membranes of A431 cells and is inhibited by VO'; and Zn2'. Interestingly, the cytosolic activity from A431 cells selectively hydrolyzes in vitro PtdIns(3)P and PtdIns(3,4)P,, whereas PtdIns(3,4,5)P, remains a very poor substrate under the same conditions. Finally, assays of phosphat-idylinositol3-kinase and 3-phosphatase activities in the pool of phosphotyrosine-containing proteins isolated from EGF-stimulated A431 cells suggest a compartmentation of these two antagonistic activities during cell activation.
The Biochemical journal, 1987
Previous work demonstrated the existence of phosphatidylinositol kinase and phosphatidylinositol phosphate kinase in rat liver nuclei, with the suggestion that these activities are in the nuclear membrane [Smith & Wells (1983) J. Biol. Chem. 258, 9368-9373]. Here we show that highly purified nuclei from Friend cells, washed free of nuclear membrane by Triton, can incorporate radiolabel from [gamma-32P]ATP into phosphatidic acid, phosphatidylinositol phosphate and phosphatidylinositol 4,5-bisphosphate. The degree of radiolabelling of phosphatidylinositol bisphosphate is highly dependent on the state of differentiation of the cells, being barely detectable in growing cells and much greater after dimethyl sulphoxide-induced differentiation; this difference is mostly due to different amounts of phosphatidylinositol phosphate in the isolated nuclei. We suggest that polyphosphoinositides are made inside the nucleus and that they have a role in chromatin function; either the phospholipids ...
Biology of the Cell, 1995
The intracellular localizations of phosphatidylinositol4,5-bisphosphate (PIP,) and of its hydrolyzing enzyme phospholipase C (PLC; in this case the p, isoform) have been evaluated by electron microscope immunocytochemistry in cells exposed to mitogenie or differentiating agents. These cells have been previously demonstrated to present a signal transduction system based on the polyphosphoinositide hydrolysis localized at the nuclear level, which can be specifically modulated by agonists. The results demonstrate that in Swiss 3T3 mouse fibroblasts mitogenically stimulated by insulin-like growth factor I (IGF-I), a rapid and transient decrease of the PIP, detectable by immunogold labeling occurs at the nuclear interior. Tbis effect appears due to the activation of the PLC p, isozyme already present in the nucleus, since no significant variations of the enzyme amount and distribution can be detected by immunolabeling. However, after 30 min of exposure to IGF-I, when the PLC pt activity is returned to basal level, a slight but significant increase of the enzyme amount is detected both in the nucleus and in the cytoplasm. On the other hand, an increased accumulation of PIP, in the nucleus, accompanied by a decrease of the intranuclear amount of PLC p, isozyme, have been observed in mouse erytbroleukemia Friend cells, induced to erytbroid differentiation by dimetbylsulfoxide (DMSO). These results indicate that quantitative immunocytochemistry represents an increment in the available methodologies to investigate the complex regulation of nuclear PIsignalling. nuclear signal transduction / polyphosphoinositide hydrolysis / 3T3 mouse fibroblasts / Friend cells / electron microscope hnmunocytochemistry '-_.'-. 'Rizzoli'.
Nuclear phosphoinositides and their roles in cell biology and disease
Critical Reviews in Biochemistry and Molecular Biology, 2011
Since the late 1980s, a growing body of evidence has documented that phosphoinositides and their metabolizing enzymes, which regulate a large variety of cellular functions both in the cytoplasm and at the plasma membrane, are present also within the nucleus, where they are involved in processes such as cell proliferation, differentiation, and survival. Remarkably, nuclear phosphoinositide metabolism operates independently from that present elsewhere in the cell. Although nuclear phosphoinositides generate second messengers such as diacylglycerol and inositol 1,4,5 trisphosphate, it is becoming increasingly clear that they may act by themselves to influence chromatin structure, gene expression, DNA repair, and mRNA export. The understanding of the biological roles played by phosphoinositides is supported by the recent acquisitions demonstrating the presence in the nuclear compartment of several proteins harboring phosphoinositide-binding domains. Some of these proteins have functional roles in RNA splicing/processing and chromatin assembly. Moreover, recent evidence shows that nuclear phospholipase Cβ1 (a key phosphoinositide metabolizing enzyme) could be somehow involved in the myelodysplastic syndrome, i.e. a hematopoietic disorder that frequently evolves into an acute leukemia. This review aims to highlight the most significant and updated findings about phosphoinositide metabolism in the nucleus under both physiological and pathological conditions.