Nuclear signalling through phospholipase C and phosphatidyl 4,5‐bisphosphate

Abstract

Phosphoinositides are key signalling intermediates with well established roles in transducing ligand mediated signals from the cell surface to the cytosol. Over recent years, strong evidence has accumulated for a role for phosphoinositides within the nucleus. Here we discuss recent advances in our understanding of a key phosphoinositide species phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P 2 ) in the nucleus. The activation/nuclear translocation mechanisms of phospholipase C family members are reviewed and the roles of nuclear PtdIns(4,5)P 2 , from the generation of the second messenger molecules inositol 1,4,5-trisphosphate and diacylglycerol to putative functions in the co-ordination of multiprotein complexes involved in transcription will be discussed.

Diagnostic and prognostic value of mRNA expression of phospholipase C β family genes in hepatitis B virus‑associated hepatocellular carcinoma

“…PLCB1 may also reduce cell damage under oxidative conditions and prevent α-synuclein aggregation (49). The amplification of PLCB1 increased K562 cell viability and enables cells to evade apoptosis (50,51); the overexpression of PLCB1 keeps Swiss 3T3 cells in the S phase of the cell cycle (52). Li et al (1) reported that upregulated PLCB1 expression is associated with tumor cell proliferation and infers a poor prognosis for HCC.…”

Up-regulated expression of phospholipase C, β1 is associated with tumor cell proliferation and poor prognosis in hepatocellular carcinoma

“… 13 Overexpression of PLCB1 is found to be sufficient to drive Swiss 3T3 cell in S phase of the cell cycle. 14 More importantly, elevated level of PLCB1 in carcinogenesis has also been recently reported. 15 Molinari et al 16 demonstrated that PLCB1 gene copy number altered in breast cancer and the overexpression of PLCB1 was associated with histological grade and proliferative index.…”

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

“…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)(2)(3)(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 ).…”

“…PLC␦, PLC␥, and PLC have also been found in the nucleus of various cell types. Although the different PLC family members share the same enzymatic function, given that these PLCs have distinct regulatory mechanisms and that they translocate to the nucleus at different cell cycle phases (14,15), it is reasonable to speculate that cells utilize specific PLC isoforms according to specific signaling cues (1).…”

“…S1-S6. 1 To whom correspondence should be addressed. partment-specific (nuclear versus cytosolic) expression of SKIP, a PtdIns(4,5)P 2 /PtdIns(3,4,5)P 3 -specific phosphatase (16,17).…”