Involvement of type I protein kinase A in the differentiation of L6 myoblast in conjunction with phosphatidylinositol 3-kinase.
To investigate the role of protein kinase A (PKA) (EC 2.7.1.37) in myogenesis, PKA activity was closely monitored during the differentiation of L6 rat skeletal myoblasts. As the differentiation proceeded, total PKA activity increased about 2-3 fold, and the protein levels of PKA RIalpha and Calpha subunits increased about 3-4 fold. We then looked at the effect of the specific inhibitor for PKA, N-[2-(p-bromocinnamy-lamino)-ethyl]-5-isoquinoline-sulfonamide (H89), on the differentiation of L6 myoblasts. H89 completely blocked the myotube formation and abolished the up-regulation of RIalpha and Ca. This inhibitory effect of H89 was dose-dependent and could be reversed upon removal of H89 from the culture medium. Furthermore, we demonstrated that specific inhibitors of phosphatidylinositol 3-kinase (PI3K), wortmannin, and LY294002 blocked the myotube formation and abolished the increase of PKA activity, which normally accompanied the differentiation of myoblasts. These results suggest that type I PKA may play a functional role(s) in the differentiation of myoblast as a putative downstream effector of the PI3K signaling pathway.
Han
Sang Yeul
SY
Institute for Molecular Biology and Genetics, Seoul National University, Korea.
Park
Dong Yoon
DY
Lee
Gwang Hee
GH
Park
Sang Dai
SD
Hong
Seung Hwan
SH
D000730:Androstadienes / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002867:Chromones / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D032448:Myoblasts, Skeletal / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013449:Sulfonamides; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D017868:Cyclic AMP-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013449:Sulfonamides; D000077191:Wortmannin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide