Adhesion-dependent control of Akt/protein kinase B occurs at multiple levels.
The protein kinase Akt, also known as Protein Kinase B, has been implicated in the survival of several cell types challenged with various apoptotic stimuli. In CCL39 lung fibroblasts, apoptosis is induced by anchorage and mitogen removal. Mitogen-induced activation of Akt is highly anchorage dependent in these cells and removal of adhesion is accompanied by a rapid loss in responsiveness to soluble agonists followed by a significant decrease in Akt abundance. Loss of the protein appears to be independent of kinase activation since the expression of a constitutively active form, gag-Akt, is also dependent upon cell adhesion. Although the disappearance of Akt is coincident with the induction of programmed cell death, it cannot be fully prevented by treatment of cells with the caspase inhibitor ZVAD or by sustained activation of the anti-apoptotic Raf/ERK pathway, in cells expressing an inducible DeltaRaf-1:ER construct. In addition, a previously unrecognized decrease in Akt mRNA levels following anchorage removal occurs suggesting that anchorage-dependent transcriptional and/or post-transcriptional mechanisms contribute to the adhesion-dependent regulation of Akt expression.
Le Gall
Maude
M
CNRS UMR 6543, Centre A. Lacassagne, Nice Cedex 2, France.
Chambard
Jean-Claude
JC
Grall
Dominique
D
Van Obberghen-Schilling
Ellen
E
D000818:Animals; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D006224:Cricetinae; D015536:Down-Regulation; D005347:Fibroblasts; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D061945:Caspase Inhibitors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases