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