1,720,965 research outputs found
Hepatocyte growth factor activates phosphoinositide 3-kinase C2 beta in renal brush-border plasma membranes
No full text--
Inositides and the nucleus and inositides in the nucleus
No full textAlthough there are many forms of evidence linking phosphoinositides to nuclear function, the substance of the links remains largely undefined. One link between inositide metabolism and the nucleus is suggested by the implication of inositol trisphosphate (IP3) in the process of nuclear envelope reassembly (Sullivan et al., 1993). That paper will be discussed below in its context, but this review will principally focus on another nuclear-inositide connection - a potential inositide cycle in the nucleus. It comes as something of a shock to see data that point to a phosphoinositide cycle entirely separate from the familiar one in the plasma membrane. Again contrary to expectation, the data suggest that the cycle is not in the nuclear membrane but appears to be within the nucleus. This aspect of inositide function has profound implications for the role of inositides in cell division and growth. For example, it makes us rethink the tumor-promoting actions of phorbol esters and the teratogenic effects of Li÷ that have been associated with inositide homeostasis. In this article the evidence of a nuclear inositide cycle and what is known about its control are reviewed, and the role it may play in eukaryotic cell function is discussed. For a discussion of proposed nuclear functions for protein kinase C and what little is known about nuclear Ca2÷, the reader is referred to a more comprehensive recent review (Irvine and Divecha, 1992)
The nuclear phosphoinositide cycle - does it play a role in nuclear Ca2+ homoeostasis?
No full textThe probable answer to this question is no. Much of the current evidence summarised elsewhere in this issue points to nuclear Ca2+ changes changing in response to cytosolic Ca2+, with little evidence for an independently controlled nuclear Ca2+ homeostasis. There are InsP3 receptors in the nuclear membrane, and it is possible that during nuclear membrane assembly the InsP3 acting on these (Sullivan and Wilson, this issue) is formed by an inositide cycle located on the assembling nuclear skeleton. But our current experimental data suggest that when the nucleus is intact, InsP3 generated by this cycle would have to exit through the nuclear pores to act on any known InsP3 receptors. Thus the nuclear inositide cycle appears more likely to serve to generate diacylglycerol to activate protein kinase C, and/or to generate inositol phosphates such as InsP2, which may have distinct intranuclear functions
Inositol lipid signalling occurs in brush-border membranes during initiation of compensatory renal growth in the rat
Full text linkUsing highly specific mass assays, concentrations of inositol lipids and 1,2-diacylglycerol (DAG) were determined in plasma membranes isolated from rat kidney cortex. Significantly higher concentrations of inositol lipids were determined in brush-border (BBM) than in basal-lateral (BLM) plasma membranes, although DAG concentrations were similar in both. After unilateral nephrectomy, a decrease in PtdIns(4,5)P2 and PtdIns4P, with a concomitant increase in DAG and translocation of protein kinase C (PKC), were observed in BBM but not in BLM isolated from the remaining kidney. On the other hand, stimulation of renal cortical slices with insulin-like growth factor II (IGF-II) or phenylephrine caused similar effects in BLM but not in BBM. Stimulation of phospholipase C activity with translocation of PKC only to BBM in one kidney was also induced by occlusion of blood flow through the contralateral kidney for 15 min. At 30 min after the occlusion was removed and reflow established, DAG concentration and the amount of PKC in BBM returned to control values. These results suggest that an early signal after unilateral nephrectomy is transmitted to cells through BBM and can be switched on and off by blood occlusion and reflow through the contralateral kidney, while hormonal signals caused by IGF-II and phenylephrine are transmitted to cells through BLM
The role of the nuclear Akt activation and Akt inhibitors in all-trans-retinoic acid-differentiated HL-60 cells
No full textThe pharmacological inhibitors of phosphoinositide 3-kinase (PI3K)/Akt pathway have been proposed in the treatment of leukemia based on their antiproliferative effects. However, several studies demonstrated the activation of PI3K in the nuclei of all-trans-retinoic acid (ATRA) - differentiated HL-60 cells, raising the possibility that PI3K/Akt-inhibitors may block antitumor properties of retinoids. The aim of the present study was to investigate the possible activation of nuclear Akt in ATRA-treated cells and to test the effects of Akt-inhibitors on ATRA-mediated differentiation. The Akt-activity was found to be increased in the nuclei and lysates of ATRA-differentiated HL-60 and NB4 cells. The down-modulation of the expression of Akt protein in HL-60 cells using siRNA reduces the CD11b expression in ATRA-treated cells. The treatment of both cell lines with the commercially available Akt inhibitors inhibited the growth of both control and ATRA-treated cells. Akt-inhibitors had no inhibitory effects on ATRA-mediated growth arrest and the expression of CD11b in HL-60 cells, but increased the percentage of control cells expressing CD11b. In contrast, the presence of Akt inhibitors reduced the expression of CD11b in ATRA-treated NB4 cells
Nuclear diacylglycerol is increased during cell proliferation in vivo
No full textHighly purified nuclei were prepared from livers and kidneys of rats undergoing compensatory hepatic or renal growth, the former being predominantly by cellular proliferation, and the latter mostly by cellular enlargement. In liver, an increase in nuclear diacylglycerol (DAG) concentration occurred between 16 and 30 h, peaking at around 20 h. At the peak of nuclear DAG production a specific translocation of protein kinase C to the nucleus could be detected; no such changes occurred in kidney. There was no detectable change in whole-cell DAG levels in liver, and the increase in DAG was only measurable in nuclei freed of their nuclear membrane. Overall, these results suggest that there is a stimulation of intranuclear DAG production, possibly through the activation of an inositide cycle [Divecha, Banfic and Irvine (1991) EMBO J. 10, 3207-3214] during cell proliferation in vivo
Presence and activation of nuclear phosphoinositide 3-kinase C2beta during compensatory liver growth.
No full text--
Nuclear diacylglycerol, the cell cycle, the enzymes and a red herring (or how we came to love phosphatidylcholine)
No full textNo abstract available
The activation of nuclear phosphoinositide 3-kinase C2 beta in all-trans-retinoic acid-differentiated HL-60 cells
No full text--
Changes in the components of a nuclear inositide cycle during differentiation in murine erythroleukaemia cells
Full text linkDifferentiation of murine erythroleukaemia cells with the chemical agent DMSO leads to a cessation of proliferation and the production of a number of erythrocyte markers such as haemoglobin. We have previously demonstrated that activation of proliferation leads to an increase in the production of nuclear diacylglycerol (DAG). Here we demonstrate that differentiation leads to a decrease in the levels of nuclear DAG and the activity of the nuclear-associated phosphoinositidase C (PIC). The change in activity appears to be due to a decrease in the mass levels of the beta 1 isoform, as demonstrated by the use of isoform-specific antibodies. Moreover, the changes correlate with the cessation of proliferation and an increase in the number of cells in G1 phase of the cell cycle, rather than with the number of cells which have differentiated. Indeed, although treatment of the cells with phorbol 12-myristate 13-acetate (PMA) inhibits the differentiation programme as assessed by haemoglobin staining, it does not inhibit the number of cells blocking in G1 of the cell cycle or the changes in nuclear DAG or PIC activity. The possible involvement of this nuclear inositide cycle during progression through the cell cycle is discussed
- …
