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.
Calera
M R
MR
Department of Biochemistry, Boston University School of Medicine, 715 Albany Street, Boston, Massachusetts, 02118, USA.
Pilch
P F
PF
D000818:Animals; D002454:Cell Differentiation; D002867:Chromones / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology* / Q000254:growth & development; D018008:Myogenin / Q000032:analysis; D009218:Myosins / Q000032:analysis; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000096:biosynthesis*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D051057:Proto-Oncogene Proteins c-akt
D002867:Chromones; D007328:Insulin; D009025:Morpholines; C503801:Myog protein, mouse; D018008:Myogenin; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011518:Proto-Oncogene Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D007334:Insulin-Like Growth Factor I; C494922:Akt2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D009218:Myosins