Insulin-like growth factor-I-dependent stimulation of nuclear phospholipase C-?1 activity in Swiss 3T3 cells requires an intact cytoskeleton and is paralleled by increased phosphorylation of the phospholipase

Martelli, Alberto M.; Cocco, Lucio; Bareggi, Renato; Tabellini, Giovanna; Rizzoli, R.; Ghibellini, Maria Dora; Narducci, Paola

doi:10.1002/(sici)1097-4644(19990301)72:3<339::aid-jcb3>3.0.co;2-l

Cited by 38 publications

(22 citation statements)

References 43 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conversely, stimulation of cells with IGF-I, which acts through a tyrosine kinase receptor, caused a rapid, 2ϳ3-fold increase in enzyme activity of nuclear PLC ␤1, while the PLC activity at plasma membrane was not affected (15). The IGF-I-stimulated activation of nuclear PLC ␤1 is transient and the enzyme activity returns to basal level within 30 min (15,31). However, the molecular mechanisms for the termination of this activation signal are currently unclear.…”

mentioning

confidence: 99%

Protein Kinase C α-mediated Negative Feedback Regulation Is Responsible for the Termination of Insulin-like Growth Factor I-induced Activation of Nuclear Phospholipase C β1 in Swiss 3T3 Cells

Xu¹,

Wang

Xu³

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

Previous studies from several independent laboratories have demonstrated the existence of an autonomous phosphoinositide (PI) cycle within the nucleus, where it is involved in both cell proliferation and differentiation. Stimulation of Swiss 3T3 cells with insulin-like growth factor-I (IGF-I) has been shown to induce a transient and rapid increase in the activity of nuclear-localized phospholipase C (PLC) ␤1, which in turn leads to the production of inositol trisphosphate and diacylglycerol in the nucleus. Nuclear diacylglycerol provides the driving force for the nuclear translocation of protein kinase C (PKC) ␣. Here, we report that treatment of Swiss 3T3 cells with Go6976, a selective inhibitor of PKC ␣, caused a sustained elevation of IGF-I-stimulated nuclear PLC activity. A time course study revealed an inverse relationship between nuclear PKC activity and the activity of nuclear PLC in IGF-I-treated cells. A time-dependent association between PKC ␣ and PLC ␤1 in the nucleus was also observed following IGF-I treatment. Two-dimensional phosphopeptide mapping and site-directed mutagenesis demonstrated that PKC promoted phosphorylation of PLC ␤1 at serine 887 in the nucleus of IGF-I-treated cells. Overexpression of either a PLC ␤1 mutant in which the PKC phosphorylation site Ser 887 was replaced by alanine, or a dominant-negative PKC ␣, resulted in a sustained activation of nuclear PLC following IGF-I stimulation. These results indicate that a negative feedback regulation of PLC ␤1 by PKC ␣ plays a critical role in the termination of the IGF-I-dependent signal that activates the nuclear PI cycle.Phospholipase C ␤ isoforms (␤1, ␤2, ␤3 and ␤4) at the plasma membrane are regulated by G protein-coupled seven-transmembrane receptors which activate heterotrimeric G␣␤␥ protein complexes upon ligand stimulation (1-3). The hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) 1 by PLC ␤s generates two well recognized second messengers, inositol 1,4,5-trisphosphate and DG. Inositol 1,4,5-trisphosphate evokes release of Ca 2ϩ from intracellular stores, while DG alone, or in concert with Ca 2ϩ , activates some isoforms of PKC (4). Mounting evidence suggests that an analogous phosphoinositide (PI) signaling, which is distinct from classic PI signaling at plasma membrane, exists in the nucleus (5-7). The presence of such a nuclear PI cycle has been demonstrated in several different cell lines (8 -11, 12), and has been shown to be important for both cell proliferation (13) and differentiation (14).The key enzyme for the initiation of nuclear PI signaling is phospholipase C (PLC) ␤1, which is the major isoform present in the nucleus of 3T3 cells (15) as well as other cell lines (16 -19). It exists as two alternatively spliced subtypes, PLC ␤1a (150 kDa) and PLC ␤1b (140 kDa) which differ only in a short region of their carboxyl termini (20). Recent studies suggest that the ␤1b form predominantly localizes in the nucleus while the ␤1a form distributes equally between the nucleus and plasma membrane (21). A nuclear locali...

show abstract

mentioning

confidence: 99%

Protein Kinase C α-mediated Negative Feedback Regulation Is Responsible for the Termination of Insulin-like Growth Factor I-induced Activation of Nuclear Phospholipase C β1 in Swiss 3T3 Cells

Xu¹,

Wang

Xu³

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…In addition, there are two splice variants of the PI-PLC-β 1 isoform, PI-PLC-β 1a and PI-PLC-β 1b , and several studies demonstrate that b splicing variant is the one that is predominantly nuclear (4,25,40,47). The "classical" PI-PLC-β, i.e.…”

Section: Nuclear Phospholipase Cmentioning

confidence: 99%

“…the one operating at the cell membrane is G-protein-regulated but there are no data confirming any role of the nuclear G protein in the activation of the nuclear enzyme. However, several studies suggested the involvement and nuclear translocation of p42/p44 mitogen-activated protein kinase (MAPK) in agonist-mediated activation of the nuclear PI-PLC-β (47,48). In a detailed study, Although the Ser982 phosphorylation was prerequisite for the PI-PLC activation, as shown in mutants carrying Ser982Gly, it was not sufficient alone, and several other components of mechanism involved in the activation of the nuclear PI-PLC still remain to be determined (Fig.…”

Section: Nuclear Phospholipase Cmentioning

confidence: 99%

“…Acinus is one of the recently identified targets of the activated nuclear Akt. (77,47) Increased (PLC assay) (77,47)* MAPK-mediated phosphorylation at Ser982 (77) No change (77,47) Immunoprecipitated with phospho-MAPK (77) IGF, HL-60 (56) Increased (PLC assay) (56) Increased DAG (56) No change (56) ND (56) −β 1β Insulin, NIH 3T3 (48) Increased (PLC assay) (48) MEK inhibitor-sensitive serine phosphorylation (48) No change (48) ND (48) IL-2, NK cells (75) Increased (PLC assay) (75) Increased DAG (75) MEK inhibitor-sensitive serine phosphorylation (75) No change (75) ND (75) FBS, HL-60 (42) Increased (PLC assay) (42) MEK inhibitor-sensitive serine phosphorylation (42) No change (42) ND (42) Hepatectomy, liver (16) Increased (PLC assay) (16) Serine phosphorylation (16) No change (16) ND (16) late G 1 /S FBS, HL-60 (42) Nocodazole, HL-60 (40) Increased (PLC assay) (40,42) MEK inhibitor-sensitive serine phosphorylation (40,42) No change (40,42) ND (40,…”

mentioning

confidence: 99%

See 1 more Smart Citation

Nuclear phospholipid signaling: phosphatidylinositol-specific phospholipase C and phosphoinositide 3-kinase

Višnjić

Banfíƈ

2007

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

Over the last 20 years, numerous studies have demonstrated the existence of nuclear phosphoinositide signaling distinct from the one at the plasma membrane. The activation of phosphatidylinositol-specific phospholipase C (PI-PLC) and phosphoinositide 3-kinase (PI3K), the generation of diacylglycerol (DAG) and the accumulation of the 3-phosphorylated phosphoinositides have been documented in the nuclei of different cell types.In this review, we summarize some recent studies of the subnuclear localization, mechanisms of activation and the possible physiological roles of the nuclear PI-PLC and PI-3 kinases in the regulation of cell cycle, survival and differentiation.

show abstract

“…Indeed, it was later shown that nuclear PLC␤1 activity is upregulated 2-fold in Swiss 3T3 cells stimulated with IGF-I (11), and down-regulation of PLC␤-1 markedly reduces the sensitivity of Swiss 3T3 cells to IGF-I (12). IGF-I induces the phosphorylation of PLC␤1, and this phosphorylation can be blocked by MAPK cascade inhibitors (PD98059 and U0126, which target MEK (MAPK/extracellular signal-regulated kinase kinase)) (13). In support of this observation, Xu et al (9) showed that PLC␤1 can be phosphorylated/activated by ERK both in vitro and in vivo in its regulatory domain.…”

mentioning

confidence: 91%

Identification of Cyclin A2 as the Downstream Effector of the Nuclear Phosphatidylinositol 4,5-Bisphosphate Signaling Network

Anderson

Rosivatz

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

In addition to the well characterized phosphoinositide second messengers derived from the plasma membrane, increasing evidence supports the existence of a nuclear phosphoinositide signaling network. The aim of this investigation was to dissect the role played by nuclear phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P 2 ) in cell cycle progression and to determine the cell cycle regulatory component(s) that are involved. A number of cytosolic/nuclear PtdIns(4,5)P 2 -deficient Swiss 3T3 cell lines were established, and their G 0 /G 1 /S cell cycle phase transitions induced by defined mitogens were examined. Our results demonstrate that nuclear PtdIns(4,5)P 2 down-regulation caused a delay in phorbol ester-induced S phase entry and that this was at least in part channeled through cyclin A 2 at the transcriptional level. In summary, these data identify cyclin A 2 as a downstream effector of the nuclear PtdIns(4,5)P 2 signaling network and highlight the importance of nuclear PtdIns(4,5)P 2 in the regulation of mammalian mitogenesis.Activation of diverse signal transduction pathways can cause quiescent cells to re-enter the cell cycle. Among these pathways, phosphoinositides (PIs) 2 represent a major class of mitogenic mediators. One of the recent developments in the field of PI signaling was the discovery of a discrete PI signaling network in the nucleus (1-4). Among the various PI species, phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P 2 ) is particularly important because it is the precursor molecule of diacylglycerol (DAG), inositol 1,4,5-trisphosphate (Ins(1,4,5)P 3 ), and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P 3 ). The known signaling functions of nuclear PtdIns(4,5)P 2 include cell proliferation and differentiation, mRNA export/processing, chromatin remodeling, and transcriptional control (5-7). In addition, many of the PtdIns(4,5)P 2 -metabolizing enzymes such as phospholipase C (PLC), type II PI kinase, protein kinase C (PKC), DAG kinases, and PDK-1 have also been shown to exist in nuclei (5, 7).In Swiss 3T3 cells, stimulation with insulin-like growth factor I (IGF-I) causes a decrease in nuclear PtdIns(4)P and PtdIns(4,5)P 2 accompanied by an increase in nuclear DAG (6). These data contrasted with those obtained when cells are stimulated with the neuropeptide bombesin, which results in similar PI changes in the plasma membrane while the nuclear PI pool was unaffected (6). These results clearly demonstrate the distinct regulation of cytosolic and nuclear PtdIns(4,5)P 2 . More recently, the synchrony between cell cycle progression and nuclear PI turnover has been demonstrated (8, 10). The fact that nuclei isolated from Swiss 3T3 cells stimulated with IGF-I exhibit a decrease in PtdIns(4,5)P 2 accompanied by an increase in DAG strongly suggests the involvement of PLC activity (6). Indeed, it was later shown that nuclear PLC␤1 activity is upregulated 2-fold in Swiss 3T3 cells stimulated with IGF-I (11), and down-regulation of PLC␤-1 markedly reduces the sensitivity of Swiss 3T3 cells t...

show abstract

Insulin-like growth factor-I-dependent stimulation of nuclear phospholipase C-?1 activity in Swiss 3T3 cells requires an intact cytoskeleton and is paralleled by increased phosphorylation of the phospholipase

Cited by 38 publications

References 43 publications

Protein Kinase C α-mediated Negative Feedback Regulation Is Responsible for the Termination of Insulin-like Growth Factor I-induced Activation of Nuclear Phospholipase C β1 in Swiss 3T3 Cells

Protein Kinase C α-mediated Negative Feedback Regulation Is Responsible for the Termination of Insulin-like Growth Factor I-induced Activation of Nuclear Phospholipase C β1 in Swiss 3T3 Cells

Nuclear phospholipid signaling: phosphatidylinositol-specific phospholipase C and phosphoinositide 3-kinase

Identification of Cyclin A2 as the Downstream Effector of the Nuclear Phosphatidylinositol 4,5-Bisphosphate Signaling Network

Contact Info

Product

Resources

About