Association of heterotrimeric G-proteins with bovine aortic phospholipase C gamma

The widely expressed phospholipase C gamma(1) (PLC gamma(1)) isoform has be en implicated in the signalling of cell growth through its ability to hydro lyse phosphatidylinositol 4,5-bisphosphate to give inositol 1,4,5-trisphosp hate and 1,2-diacylglycerol. Stimulation of PLC gamma(1) activity occurs up on phosphorylation of specific tyrosine residues, although it is unclear ho w this phosphorylation actually stimulates catalytic activity. Indeed recen t reports suggest that accessory factors such as GTP-binding proteins may a lso be required for complete activation of PLC gamma(1) in some cells. This may be of importance in vascular smooth muscle where traditionally G-prote in linked PLC beta isoforms are often absent. Here, we show that bovine aor tic PLC gamma(1) activity is substantially enhanced by both GTP gamma S and sodium fluoride. Similarly, immunoprecipitated PLC gamma(1) is associated with an approximately 40 kDa GTP gamma S-binding protein and both G alpha(i ) and G alpha(q) were detected in this immunoprecipitate. This data suggest s that bovine aortic PLC gamma(1) is both associated with, and may be activ ated by, heterotrimeric G-proteins. (C) 1999 Academic Press.