Structural and mechanistic aspects of phospholipase Cγ regulation

The role of different PI-PLC isoforms in cell signaling and control of various cellular functions has been extensively studied. Of the four families of PI-PLC, PLCγ family (PLCγ1 and PLCγ2) has been identified as an important component in pathways triggered by growth factor receptors in normal and cancer cells. Similarly, PLCγ isoforms have a crucial role in signaling in hematopoietic cells. Insights into molecular mechanisms of PLCγ activation provided a basis for the model suggesting two regulatory steps; the first step is related to translocation to the plasma membrane and the second step involves further changes resulting in high rate of substrate hydrolysis, presumably by overcoming intramolecular inhibition. Although the enzyme activity of PLCγ and other PI-PLC families can be inhibited by the compound U73122, there is a need for more specific inhibitors to assess further the signaling and mechanistic aspects of PLCγ function.