Regulation of neutrophil apoptosis by modulation of PKB/Akt activation.
The serine/threonine kinase, Akt, also known as PKB (Protein Kinase B) is one important signal transduction pathway that mediates the delay of neutrophil apoptosis caused by inflammatory mediators. Proteins controlled by the PKB/Akt pathway have been reported to prevent or reverse apoptotic-signaling pathways and regulate cell survival. In this review we discuss the role of PKB/Akt activation in the regulation of neutrophil activation during inflammation, and the importance of resolving the inflammatory response by inhibiting PKB/Akt activation and neutrophil survival. Furthermore, we introduce the concept of a dynamic Akt signal complex that is altered when an extracellular signal is initiated such that changes in protein-protein interactions within the Akt signal complex regulates Akt activity and cell survival. Various substrates of PKB/Akt as well as positive and negative regulators of PKB/Akt activation are discussed which in turn inhibit or enhance cellular survival.
Rane
Madhavi J
MJ
Department of Medicine, University of Louisville, Louisville, Kentucky, Louisville, Kentucky, USA. mjrane01@gwise.louisville.edu
Klein
Jon B
JB
D017209:Apoptosis / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D009504:Neutrophils / Q000166:cytology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism* / Q000502:physiology
D051057:Proto-Oncogene Proteins c-akt