Introduction

For more than 30 years, the inositol phospholipids and the activities of various phospholipases have been intimately associated with fundamental aspects of the stimulation of platelets. Works of various scientific groups led to the initial discoveries in the 1970s and 1980s that related the metabolism of phospholipids to the early platelet physiological responses such as shape change, secretion, and aggregation. In many instances, these findings were used to develop signal transduction concepts in many other biological systems. The products resulting from activation of these phospholipases represent myriad second messengers with relevant biological roles. Phospholipases and their substrates and products are central to the action of many receptors, transducers, and protein kinases, as well as to the mobilization of ions. This chapter describes the roles of phospholipase C and phospholipase D in signal transduction, and it discusses how these activities interplay in a network of pathways leading to physiological responses.

Overview of phospholipase C

Phosphoinositide-specific phospholipase C (PLC) plays an essential role in receptor-mediated platelet activation. The mammalian PLCs represent a family of Ca2+-dependent enzymes showing a substrate preference for phosphatidylinositol 4, 5-bisphosphate (PIP2) over phosphatidylinositol 4-phosphate (PIP) or phosphatidylinositol (PI). Hydrolysis of PIP2 by PLC leads to the generation of two important intracellular messengers: inositol 1, 4, 5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 is a soluble molecule that promotes the rapid release of Ca2+ from internal stores.