title: Phosphatidylinositol 3-kinase regulates differentiation of H9c2 cardiomyoblasts mainly through the protein kinase B/Akt-independent pathway.
abstract: Phosphatidylinositol 3-kinase (PI3-kinase) is known to be a crucial regulator of muscle differentiation. However, its downstream pathway for this function is quite obscure. In this experiment we demonstrated the regulatory mechanism of the differentiation of H9c2 cardiomyoblasts, focusing on PI3-kinase, protein kinase B/Akt (PKB/Akt) and p42/44 mitogen-activated protein kinase (p42/44 MAPK). When H9c2 cells stably transfected with a constitutively active p110 (H9c2-p110*), a constitutively active PKB/Akt (H9c2-Akt), and an empty vector (H9c2-con) were induced to differentiate, H9c2-p110* cells differentiated fastest, followed by H9c2-Akt cells. H9c2-con cells differentiated at the slowest rate. Consistent with this result, LY294002 completely blocked differentiation of all these transfected cell lines, whereas PD098059 had no effect on their differentiation. When H9c2-p110* cells were transiently transfected with a dominant negative form of PKB/Akt, differentiation was not affected. Taken together, we concluded that PI3-kinase, but not p42/44 MAPK, regulates differentiation of H9c2 cardiomyoblasts mainly through the PKB/Akt-independent pathway.
authors.affiliation: School of Natural Science, Hanyang University, Seoul, 133-791, Korea.
authors.forename: J M
authors.initials: JM
authors.lastname: Kim
authors.forename: M Y
authors.initials: MY
authors.lastname: Yoon
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: S S
authors.initials: SS
authors.lastname: Kim
authors.forename: I
authors.initials: I
authors.lastname: Kang
authors.forename: J
authors.initials: J
authors.lastname: Ha
authors.forename: S S
authors.initials: SS
authors.lastname: Kim
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005799:Genes, Dominant / Q000235:genetics; D006321:Heart / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009154:Mutation; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
chemical_list: D002867:Chromones; D005419:Flavonoids; D007328:Insulin; D019950:Mitogen-Activated Protein Kinase 1; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494920:Akt1 protein, rat; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one