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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Thuerauf, D. J. Glembotski, C. C. Zechner, D. Mcdonough, P. M. Hanford, D. S. |
| Description | Author Affiliation: Zechner D ( Department of Biology and Molecular Biology Institute, San Diego State University, California 92182, USA.) |
| Abstract | Three hallmark features of the cardiac hypertrophic growth program are increases in cell size, sarcomeric organization, and the induction of certain cardiac-specific genes. All three features of hypertrophy are induced in cultured myocardial cells by $α_{1}-$ adrenergic receptor agonists, such as phenylephrine (PE) and other growth factors that activate mitogen- activated protein kinases (MAPKs). In this study the MAPK family members extracellular signal–regulated kinase (ERK), c-jun $NH_{2}-terminal$ kinase (JNK), and p38 were activated by transfecting cultured cardiac myocytes with constructs encoding the appropriate kinases possessing gain-of-function mutations. Transfected cells were then analyzed for changes in cell size, sarcomeric organization, and induction of the genes for the A- and B-type natriuretic peptides (NPs), as well as the α-skeletal actin (α-SkA) gene. While activation of JNK and/or ERK with $MEKK1_{COOH}$ or Raf-1 BXB, respectively, augmented cell size and effected relatively modest increases in NP and α-SkA promoter activities, neither upstream kinase conferred sarcomeric organization. However, transfection with MKK6 (Glu), which specifically activated p38, augmented cell size, induced NP and α-Ska promoter activities by up to 130-fold, and elicited sarcomeric organization in a manner similar to PE. Moreover, all three growth features induced by MKK6 (Glu) or PE were blocked with the p38-specific inhibitor, SB 203580. These results demonstrate novel and potentially central roles for MKK6 and p38 in the regulation of myocardial cell hypertrophy. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 1 |
| Volume Number | 139 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 1997-10-06 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Calcium-Calmodulin-Dependent Protein Kinases Physiology Gene Expression Regulation Mitogen-Activated Protein Kinases Myocardium Enzymology Metabolism Sarcomeres Animals Antagonists & Inhibitors Cardiomegaly Genetics Pathology Cell Division Drug Effects Cell Size Cells, Cultured Enzyme Inhibitors Pharmacology Imidazoles MAP Kinase Kinase 6 Cytology Phenylephrine Pyridines P38 Mitogen-Activated Protein Kinases Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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