Nuclear phospholipase C: Involvement in signal transduction

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• 作者：Lucia Manzoli ; Alberto M. Martelli ; Anna Maria Billi ; Irene Faenza ; Roberta Fiume and Lucio Cocco
• 关键词：Inositol lipids ; Inositol phosphates ; Diacylglycerol ; Protein kinase C ; Proliferation ; Differentiation
• 刊名：Progress in Lipid Research
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：44
• 期：4
• 页码：185-206
• 全文大小：440 K

文摘

During the past years, several independent laboratories have highlighted the presence of nuclear signaling pathways based on lipid hydrolysis, which are not a mere duplication of those occurring at the plasma membrane. Among the enzymes of the cycle, nuclear phosphoinositide-specific phospholipase C (PI-PLC) has been analyzed quite extensively. In this context, PI-PLCβ₁ appears to play a key role as a check point in the G1 phase of the cell cycle. It has also been shown that its activation and/or up-regulation is upon the control of type 1 insulin-like growth factor receptor (IGF-R) in both mouse fibroblast and myoblasts, suggesting that its signaling activity is essential for the normal behavior of the cell, at least in culture. The recent discovery of a possible involvement of the deletion of PI-PLCβ₁ gene in the progression of myelodysplastic syndrome (MDS) to acute myeloid leukemia (AML) in humans strengthens the contention that nuclear PI-PLC signaling is essential for physiogical processes such as cell growth and differentiation. Even though PI-PLCβ₁ is present and does not translocate to eukaryotic nuclei, this organelle, even though only in some conditions contains also PI-PLCγ₁ which acts not only as a PI-PLC but also as guanine nucleotide exchange factor (GEF) for PI 3-kinase enhancer (PIKE) and is somehow linked to PI 3-kinase (PI3K) activity. Also members of PI-PLCδ family are shuttling from the nucleus to the cytoplasm and return and are possibly involved in the control of cell growth. We must also take into account the presence in the nucleus of other phospholipases such as phospholipase A2 (PLA₂) and phospholipase D (PLD), which also exert a signaling activity upon external stimuli.

On the whole this review highlights the latest development in the PI-PLC cycle in the nucleus, which in terms of activation, regulation and down-stream targets differs substantially from that located at the plasma membrane.