Themes in Signaling

 
At least two separate molecular events are required for RTK-induced activation of signaling molecules. As many protein targets of RTKs are located at the cell membrane, translocation to th e cell membrane is essential for activation of many effector proteins. Activation of PKB (also known as Akt) by membrane translocation. PtdIns(3,4,5)P3 generated in response to growth factor stimulation serves as a binding site for the PH domains of PDK1 and PKB. Membrane translocation is accompanied by release of an autoinhibition leading to activation of PDK1 and PKB kinase activities. Full activation of PKB requires phosphorylation of PDK1 (and also by PDK2?). Activated PKB phosphorylates a variety of target proteins that prevent apoptotic death and regulate various metabolic processes.