Regulation of nuclear phospholipase C activity.

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-PLCβ1, 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 Gαq/α11 and Gβg subunits, there is yet no evidence that qα/α11 is present within the nuclear compartment, neither GTP-γ-S nor AlF4 can stimulate PI-PLCβ1 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-PLCβ1 and triggers its signalling, hinting at a separate pathway of regulation depending on the subcellular location of PI-PLCβ1. The difference in the regulation of the activity of PI-PLCβ1mirrors 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.