16.5 Phosphoinositide Signaling Pathways

In previous sections, we have seen how the transduction of signals from receptor tyrosine kinases (RTKs) and cytokine receptors begins with the formation of multiprotein complexes associated with the plasma membrane (see Figures 16-10 and 16-14) and how these complexes initiate the Ras/MAP kinase pathway. Here we discuss how these same receptors initiate signaling pathways that involve as intermediates special phosphorylated phospholipids derived from phosphatidylinositol. As discussed in Chapter 15, these membrane-bound lipids are collectively referred to as phosphoinositides. These phosphoinositide signaling pathways include several enzymes that synthesize different phosphoinositides on the cytosolic face of the plasma membrane as well as cytosolic proteins with domains that can bind to these molecules and that are thus recruited to the cytosolic surface of the plasma membrane. In addition to the short-term effects on cell metabolism we encountered in Chapter 15, these phosphoinositide pathways have long-term effects on patterns of gene expression. We will see that phosphoinositide pathways end with a variety of kinases, including protein kinase C (PKC) and protein kinase B (PKB), that play key roles in cell growth and metabolism. As an example, we will see later in the chapter how insulin activation of PKB plays a key role in stimulating glucose import into muscle.