| First Author | Ghosh-Choudhury N | Year | 2003 |
| Journal | J Biol Chem | Volume | 278 |
| Issue | 24 | Pages | 21998-2005 |
| PubMed ID | 12663654 | Mgi Jnum | J:83869 |
| Mgi Id | MGI:2664005 | Doi | 10.1074/jbc.M302277200 |
| Citation | Ghosh-Choudhury N, et al. (2003) Phosphatidylinositol 3-kinase regulates bone morphogenetic protein-2 (BMP-2)-induced myocyte enhancer factor 2A-dependent transcription of BMP-2 gene in cardiomyocyte precursor cells. J Biol Chem 278(24):21998-2005 |
| abstractText | The growth and differentiation factor bone morphogenetic protein-2 (BMP-2) regulates cardiac development during vertebrate embryogenesis. In cardiac precursor cells, BMP-2 has recently been shown to induce expression of cardiac transcription factors, including myocyte enhancer factor 2A (MEF-2A). The specific signal transduction mechanism by which BMP-2 regulates these actions is not known. We investigated the role of phosphatidylinositol (PI) 3-kinase in regulating these processes in cardiomyocyte precursor CL6 cells. BMP-2 increased PI 3-kinase activity in these cells in a time-dependent manner, resulting in increased expression of sarcomeric myosin heavy chain (MHC) and MEF-2A. Inhibition of PI 3-kinase abolished these actions of BMP-2, indicating the involvement of PI 3-kinase in these processes. Furthermore, BMP-2 stimulated specific protein.DNA complex formation when an MEF-2 DNA recognition element was used as probe. Antibody supershift assay confirmed the presence of MEF-2A in this protein.DNA complex. Inhibition of PI 3-kinase activity completely prevented the MEF-2A.DNA complex formation. BMP-2 also increased transcription of a reporter gene driven by an MEF-2-specific DNA element in a PI 3-kinase-dependent manner. Ectopic expression of MEF-2A increased BMP-2 transcription to the same extent induced by BMP-2, indicating that MEF-2A may participate in BMP-2 autoregulation in CL6 cells. Expression of dominant negative PI 3-kinase completely abolished BMP-2-induced as well as MEF-2A-mediated BMP-2 transcription. Furthermore expression of MEF-2A increased MHC expression in a PI 3-kinase-dependent manner. Together these data provide the first evidence that BMP-2-induced PI 3-kinase signaling regulates MEF-2A expression and define a mechanism of MEF-2A-dependent BMP-2 transcription. |
