The involvement of
phospholipids and especially
polyphosphoinositides in cellular signalling has been documented in detail over the last 20 years. Besides the membrane localisation the nucleus also has been show to be a site for both the synthesis and hydrolysis of the phosphorylated forms of
phosphatidylinositol. Previous observations dealing with signal transduction have established
phospholipase C, specific for
inositol lipids (PLC), an important step in the
inositol lipid cycle. Of the several known PLC
isoforms the type beta 1 is of particular interest because of its reported nuclear localisation, in addition to its presence at the plasma membrane. Indeed, investigations from our laboratory and others have shown the existence in several cell types of an autonomous intranuclear inositide cycle endowed with both conventional
lipid kinases and PLC. Moreover, both the stimulation and the inhibition of the nuclear
PLC beta 1 under different stimuli implicate this PLC
isoform as a key
enzyme for
mitogen-activated cell growth as well as for differentiation. These findings have prompted us to better characterise the nuclear
PLC beta 1. The
isoform beta 1 has been studied as a possible target for anti-
cancer drugs and as an inducer, via
diacylglycerol generation, of the translocation of specific
protein kinase C (PKC)
isozyme to the nucleus. The chromosome mapping of
PLC beta 1 gene has been carried out and the effect of its knock-out by means of antisense
cDNA has been determined.