Phospholipase C-γ as a Signal-Transducing Element

Abstract

A ubiquitous signaling event in hormonal responses is the phospholipase C (PLC)-catalyzed hydrolysis of phosphatidylinositol 4,5-bisphosphate to produce the metabolite second messenger molecules inositol 1,4,5-trisphosphate and diacylglycerol. The former provokes a transient increase in intracellular free Ca2+, while the latter serves as a direct activator of protein kinase C. In tyrosine kinase-dependent signaling pathways this reaction is mediated by the PLC-γ isozymes. These are direct substrates of many tyrosine kinases in a wide variety of cell types. The mechanism of PLC-γ activation 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 biochemistry of PLC-γ is at a more advanced state than a clear understanding of exactly how this signaling element functions in the generation of a mitogenic response.