Protein kinase B beta/Akt2 plays a specific role in muscle differentiation.
Insulin-like growth factors positively regulate muscle differentiation through activation of the phosphatidylinositol 3-kinase/protein kinase B (PKB/Akt) signaling pathway. Here, we compare the role of the two closely related alpha (Akt1) and beta (Akt2) isoforms of PKB in muscle differentiation. During differentiation of C2.7 or L6D2 myoblasts, PKBbeta was up-regulated whereas expression of PKBalpha was unaltered. Although the two isoforms were found active in both myoblasts and myotubes, cell fractionation experiments indicated that they displayed distinct subcellular localizations in differentiated cells with only PKBbeta localized in the nuclei. In a transactivation assay, PKBbeta (either wild-type or constitutively active) was more efficient than PKBalpha in activating muscle-specific gene expression. Moreover, microinjection of specific antibodies to PKBbeta inhibited differentiation of muscle cells, whereas control or anti-PKBalpha antibodies did not. On the other hand, microinjection of the anti-PKBalpha antibodies caused a block in cell cycle progression in both non muscle and muscle cells, whereas anti-PKBbeta antibodies had no effect. Taken together, these results show that PKBbeta plays a crucial role in the commitment of myoblasts to differentiation that cannot be substituted by PKBalpha.
Vandromme
M
M
Institut de Genetique Humaine, CNRS, UPR 1142, 141 Rue de la Cardonille, 34396 Montpellier Cedex 4, France.
Rochat
A
A
Meier
R
R
Carnac
G
G
Besser
D
D
Hemmings
B A
BA
Fernandez
A
A
Lamb
N J
NJ
D002454:Cell Differentiation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008845:Microinjections; D009132:Muscles / Q000166:cytology* / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D015533:Transcriptional Activation
D011518:Proto-Oncogene Proteins; C494918:AKT1 protein, human; C494921:AKT2 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt