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-PLQCß1, 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 Gaq/a11 and Gßy subunits, there is yet no evidence that qa/a11 is present within the nuclear compartment, neither GTP-y-S nor AlF4 can stimulate PI-PLCß1 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-PLCß1 and triggers its signal­ling, hinting at a separate pathway of regulation depending on the subcellular loca­tion of PI-PLCß1. The difference in the regulation of the activity of PI-PLCß1 mirrors 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.