ABSTRACT
There are a number of extracellular signals or insults that induce apoptosis and a variety of growth factors and cytokines that can promote cell survival in the presence of an apoptotic signal. The cell execution machinery and the immediate upstream regulators of this machinery are rapidly being unravelled. An important question then, is what signal transduction pathways link membrane events to the apoptotic effector machinery? There is good evidence that stress activated protein kinases (SAPKs) are activated by signals that induce apoptosis and that constitutive activation of the SAPKs can induce apoptosis. It is also clear that activation of phosphoinositide 3-OH kinase (PI3K) and the Akt serine/threonine kinase can promote cell survival in the presence of stimuli that normally induce apoptosis. A similar protective role for the mitogen activated protein kinase (MAPK) cascade has been proposed. While it is clear that these well defined signalling cascades play a role in regulating apoptosis, the critical targets of these cascades are largely unknown, in other words, the wiring diagrams connecting to the effectors of apoptosis are incomplete. The aim of this chapter is to briefly review the organization and mechanisms of activation of the PI3K/ Akt, MAPK and SAPK pathways and discuss some of the data that implicate these pathways in signalling for cell survival or apoptosis. Other pathways that signal for apoptosis are reviewed elsewhere in this book.
