Advan. Enzyme Regul. 47 (2007) 2–9 Nuclear inositide signaling: An appraisal of phospholipase C b1 behavior in myelodysplastic and leukemia cells Lucio Cocco a,Ã , Matilde Y. Follo a , Irene Faenza a , Alberto Bavelloni b , Anna Maria Billi a , Alberto M. Martelli a,c,d , Lucia Manzoli a a Cellular Signalling Laboratory, Department of Anatomical Sciences, University of Bologna, via Irnerio 48, 40126 Bologna, Italy b Laboratory of Cell Biology and Electron Microscopy, IOR, Bologna, Italy c ITOI-CNR, Bologna Unit, c/o IOR, Bologna, Italy d School of Pharmacy, University of Bologna, Italy Introduction Phospholipids are key regulators of a large number of cellular functions and do not act merely as structural components of biological membranes. Among phospholipids, polyphosphoinositides are key players in a number of signaling pathways. Inositol phospholipids are quantitatively minor constituents of cell membranes. Indeed, phosphatidylinositol (PI) typically comprises approximately 10% of total membrane lipid. This hints at the fact that inositol lipids are likely to play a major functional role. The pioneering work of Hokin and Hokin (1953) published more than 50 years ago, showed that stimulation of pancreas and brain slices with cholinergic agonists was accompanied by enhanced incorporation of [ 32 P]orthophosphate selectively into PI, but not into other phospholipids. We are now aware that this effect reflects a compensatory resynthesis of phosphoinositides which follows the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) by receptor-regulated forms of phosphoinositide-specific phos- pholipase C (PI-PLC). This reaction generates two products, inositol 1,4,5-trisphosphate ARTICLE IN PRESS www.elsevier.com/locate/advenzreg 0065-2571/$ - see front matter r 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.advenzreg.2006.12.003 Ã Corresponding author. Tel.: +39 051 2091564; fax: +39 051 251735. E-mail address: lcocco@biocfarm.unibo.it (L. Cocco).