PMID- 10375400 OWN - NLM STAT- MEDLINE DCOM- 19990715 LR - 20211203 IS - 0003-9861 (Print) IS - 0003-9861 (Linking) VI - 367 IP - 1 DP - 1999 Jul 1 TI - Phosphatidylinositol 3-kinase regulates differentiation of H9c2 cardiomyoblasts mainly through the protein kinase B/Akt-independent pathway. PG - 67-73 AB - 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. CI - Copyright 1999 Academic Press. FAU - Kim, J M AU - Kim JM AD - School of Natural Science, Hanyang University, Seoul, 133-791, Korea. FAU - Yoon, M Y AU - Yoon MY FAU - Kim, J AU - Kim J FAU - Kim, S S AU - Kim SS FAU - Kang, I AU - Kang I FAU - Ha, J AU - Ha J FAU - Kim, S S AU - Kim SS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Arch Biochem Biophys JT - Archives of biochemistry and biophysics JID - 0372430 RN - 0 (Chromones) RN - 0 (Flavonoids) RN - 0 (Insulin) RN - 0 (Morpholines) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Proto-Oncogene Proteins) RN - 0 (RNA, Messenger) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - EC 2.7.11.1 (Akt1 protein, rat) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM MH - Animals MH - Cell Differentiation/drug effects MH - Cell Line MH - Cell Size/drug effects MH - Chromones/pharmacology MH - Flavonoids/pharmacology MH - Genes, Dominant/genetics MH - Heart/drug effects MH - Insulin/pharmacology MH - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/metabolism MH - Morpholines/pharmacology MH - Mutation MH - Myocardium/*cytology/metabolism MH - Phosphatidylinositol 3-Kinases/genetics/*metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Phosphorylation/drug effects MH - Precipitin Tests MH - *Protein Serine-Threonine Kinases MH - Proto-Oncogene Proteins/genetics/*metabolism MH - Proto-Oncogene Proteins c-akt MH - RNA, Messenger/genetics/metabolism MH - Rats MH - *Signal Transduction/drug effects MH - Transfection EDAT- 1999/06/22 00:00 MHDA- 1999/06/22 00:01 CRDT- 1999/06/22 00:00 PHST- 1999/06/22 00:00 [pubmed] PHST- 1999/06/22 00:01 [medline] PHST- 1999/06/22 00:00 [entrez] AID - S0003-9861(99)91232-8 [pii] AID - 10.1006/abbi.1999.1232 [doi] PST - ppublish SO - Arch Biochem Biophys. 1999 Jul 1;367(1):67-73. doi: 10.1006/abbi.1999.1232.