title: Regulation of nuclear phospholipase C activity.
abstract: A body of evidence, linking inositide-specific phospholipase C (PI-PLC) to the nucleus, is quite extensive. The main isoform in the nucleus is PI-PLCbeta1, whose activity is up-regulated in response to insulin-like growth factor-1 (IGF-1) or insulin stimulation. Whilst at the plasma membrane this PI-PLC is activated and regulated by Galphaq/alpha(11) and Gbetagamma subunits, there is yet no evidence that qalpha/alpha(11) is present within the nuclear compartment, neither GTP-gamma-S nor AlF4 can stimulate PI-PLCbeta1 activity in isolated nuclei. Here we review the evidence that upon occupancy of type 1 IGF receptor there is translocation to the nucleus of phosphorylated mitogen-activated protein kinase (MAPK) which phosphorylates nuclear PI-PLCbeta1 and triggers its signalling, hinting at a separate pathway of regulation depending on the subcellular location of PI-PLCbeta1. The difference in the regulation of the activity of PI-PLCbeta1mirrors the evidence that nuclear and cytoplasmatic inositides can differ markedly in their signalling capability. Indeed, we do know that agonists which affect nuclear inositol lipid cycle at the nucleus do not stimulate the one at the plasma membrane.
authors.affiliation: Cellular Signalling Laboratory, Department of Anatomical Sciences, University of Bologna, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Manzoli
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Billi
authors.forename: Alberto Maria
authors.initials: AM
authors.lastname: Martelli
authors.forename: Lucio
authors.initials: L
authors.lastname: Cocco
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002467:Cell Nucleus / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D050356:Lipid Metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008954:Models, Biological; D010738:Type C Phospholipases / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D007328:Insulin; D007334:Insulin-Like Growth Factor I; D010738:Type C Phospholipases