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The Akt-glycogen synthase kinase 3beta pathway regulates transcription of atrial natriuretic factor induced by beta-adrenergic receptor stimulation in cardiac myocytes.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Morisco, Carmine Zebrowski, David C. Condorelli, Gianluigi Tsichlis, Philip N. Vatner, Stephen F. Sadoshima, Junichi |
| Copyright Year | 2000 |
| Abstract | We examined the mechanism of atrial natriuretic factor (ANF) transcription by isoproterenol (ISO), an agonist for the beta-adrenergic receptor (betaAR), in cardiac myocytes. ISO only modestly activated members of the mitogen-activated protein kinase family. ISO-induced ANF transcription was not affected by inhibition of mitogen-activated protein kinases, whereas it was significantly inhibited by KN93, an inhibitor of Ca(2+)/calmodulin-dependent kinase (CaM kinase II). Production of 3'-phosphorylated phosphatidylinositides (3 phosphoinositides) was also required for ISO-induced ANF transcription. ISO caused phosphorylation (Ser-473) and activation of Akt through CaM kinase II- and 3 phosphoinositides-dependent mechanisms. Constitutively active Akt increased myocyte surface area, total protein content, and ANF expression, whereas dominant negative Akt blocked ISO-stimulated ANF transcription. ISO caused Ser-9 phosphorylation and decreased activities of GSK3beta. Overexpression of GSK3beta inhibited ANF transcription, which was reversed by ISO. ISO failed to reverse the inhibitory effect of GSK3beta(S9A), an Akt-insensitive mutant. Kinase-inactive GSK3beta increased ANF transcription. Cyclosporin A partially inhibited ISO-stimulated ANF transcription, indicating that calcineurin only partially mediates ANF transcription. These results suggest that both CaM kinase II and 3 phosphoinositides mediate betaAR-induced Akt activation and ANF transcription in cardiac myocytes. Furthermore, betaAR-stimulated ANF transcription is predominantly mediated by activation of Akt and subsequent phosphorylation/inhibition of GSK3beta. |
| Starting Page | 21 |
| Ending Page | 26 |
| Page Count | 6 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jbc.org/content/275/19/14466.full.pdf |
| PubMed reference number | 10799529v1 |
| Volume Number | 275 |
| Issue Number | 19 |
| Journal | The Journal of biological chemistry |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adrenergic Receptor Adrenergic beta-Antagonists Atrial Natriuretic Factor Calcineurin Calcium Cyclosporine Dominant-Negative Mutation Glycogen (Starch) Synthase Glycogen Synthase Kinases Growth Factor Heart Atrium Inactive - Biochemical Activity Level Isoproterenol Mitogen-Activated Protein Kinases Mitogens Muscle Cells Myocytes, Cardiac Natriuretic Hormones Phosphatidylinositols Proto-Oncogene Proteins c-akt beta-2 Adrenergic Receptors calmodulin-dependent protein kinase II glycogen synthase kinase 3 beta |
| Content Type | Text |
| Resource Type | Article |
