Phospholipase C-gamma as a signal-transducing element

A ubiquitous signaling event in hormonal responses is the phospholipase C ( PLC)-catalyzed hydrolysis of phosphatidylinositol 4,5-bisphosphate to produ ce the metabolite second messenger molecules inositol 1,4,5-trisphosphate a nd diacylglycerol. The former provokes a transient increase in intracellula r free Ca2+, while the latter serves as a direct activator of protein kinas e C. In tyrosine kinase-dependent signaling pathways this reaction is media ted by the PLC-gamma isozymes. These are direct substrates of many tyrosine kinases in a wide variety of cell types. The mechanism of PLC-gamma activa tion involves its association with and phosphorylation by receptor and non- receptor tyrosine kinases, as well as interaction with specialized adaptor molecules and, perhaps, other second messenger molecules. However, the bioc hemistry of PLC-gamma is at a more advanced state than a clear understandin g of exactly how this signaling element functions in the generation of a mi togenic response. (C) 1999 Academic Press.