Induction of Akt-2 correlates with differentiation in Sol8 muscle cells

Phosphatidylinositol 3-kinase is involved in the regulation of muscle cell differentiation. The serine/threonine kinase Akt has been implicated in the signaling pathway downstream of PI3-kinase. Here we demonstrate that differentiation of Sol8 skeletal muscle cells is associated with a marked increase in endogenous Akt-2 protein. Myogenesis was induced by three different conditions: cell confluence, low serum or treatment with insulin or insulin-like growth factor-I. Differentiation by cell confluence resulted in an increase in the endogenous protein content and activation of Akt-2. Low serum conditions induced a dramatic raise in Akt-2 protein levels which correlates with the induction of the muscle cell differentiation marker myogenin. Treatment of Sol8 cells with the PI3-kinase inhibitor LY294002 prevented the expression of myogenin as effectively as the increase in Akt-2 content induced by low-serum conditions. Similarly, differentiation of Sol8 cells stimulated by 50 nM insulin or 10 nM IGF-I markedly increased Akt-2 protein levels. These results and the recent observation that active Akt translocates to the cell nucleus (J. Biol. Chem. 272, 30491-30497; 31515-31524, 1997) suggests that Akt-2 might play a crucial role in the initiation of the genetic program responsible for muscle cell differentiation.