Activation of Akt2 Inhibits anoikis and apoptosis induced by myogenic differentiation.
Akt2, a homolog of Akt1, encodes a serine/threonine protein kinase that is amplified in ovarian and pancreatic cancers. The antiapoptotic activities of the Akt1 proto-oncogene product have been well documented, but the role of Akt2 in cellular survival is poorly understood. Here, we demonstrate that Akt2 mRNA, protein and kinase activity are upregulated during serum deprivation-induced C2C12 cell myogenic differentiation, a process that is associated with the acquisition of an apoptosis-resistant phenotype. Transient transfection of plasmids encoding wild-type and constitutively-active Akt2 conferred resistance against apoptosis in differentiating C2C12 cells, while a kinase-negative Akt2 construct did not. Adenovirus-mediated transfer of the constitutively-active Akt2 cDNA also suppressed apoptosis during serum deprivation-induced myogenic differentiation and it protected cells from apoptosis induced by cell detachment. These data indicate that Akt2 functions as an anti-apoptotic gene during cellular differentiation, a property that may contribute to its oncogenicity.
Fujio
Y
Y
Division of Cardiovascular Research, St. Elizabeth's Medical Center, Boston, MA 02135, USA.
Mitsuuchi
Y
Y
Testa
J R
JR
Walsh
K
K
D023102:Anoikis; D017209:Apoptosis; D002454:Cell Differentiation; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D024510:Muscle Development / Q000502:physiology*; D010770:Phosphotransferases / Q000096:biosynthesis* / Q000187:drug effects* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt; D014162:Transfection; D015854:Up-Regulation
D016895:Culture Media, Serum-Free; D011518:Proto-Oncogene Proteins; D010770:Phosphotransferases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt