Résumé
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 α (Akt1) and β (Akt2) isoforms of PKB in muscle differentiation. During differentiation of C2.7 or L6D2 myoblasts, PKBβ was up-regulated whereas expression of PKBα 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 PKBβ localized in the nuclei. In a transactivation assay, PKBβ (either wild-type or constitutively active) was more efficient than PKBα in activating muscle-specific gene expression. Moreover, microinjection of specific antibodies to PKBβ inhibited differentiation of muscle cells, whereas control or anti-PKBα antibodies did not. On the other hand, microinjection of the anti-PKBα antibodies caused a block in cell cycle progression in both non muscle and muscle cells, whereas anti-PKBβ antibodies had no effect. Taken together, these results show that PKBβ plays a crucial role in the commitment of myoblasts to differentiation that cannot be substituted by PKBα.