HRas-dependent pathways can activate morphological and genetic markers of cardiac muscle cell hypertrophy

Thorburn, A., Thorburn, J., Chen, S. Y., Powers, S., Shubeita, H. E., Feramisco, J. R., Chien, K. R. (January 1993) HRas-dependent pathways can activate morphological and genetic markers of cardiac muscle cell hypertrophy. Journal of Biological Chemistry, 268 (3). pp. 2244-9. ISSN 0021-9258

URL: http://www.ncbi.nlm.nih.gov/pubmed/8420993

Abstract

We have investigated the role of the proto-oncogene HRas in cardiac cell growth and hypertrophy. By direct needle microinjection of activated Ras protein into primary neonatal rat ventricular cardiac myocytes, we find that, unlike many other cell types, Ras does not induce DNA synthesis in these cells. However, injection of activated Ras does induce expression of both the c-Fos and atrial natriuretic factor (ANF) genes. Expression of both these genes is associated with the hypertrophic response in ventricular myocytes suggesting that Ras is involved in the hypertrophic signalling pathway. Ras injection also causes morphological changes in the cells so that they increase in profile and show changes in the organization of the contractile apparatus. Further support for a role for Ras in the hypertrophic response was obtained from studies showing that activated Ras stimulates ANF promoter activity in transient transfection assays. We also show that a dominant interfering Ras mutant inhibits the hypertrophic stimulation of the ANF promoter by phenylephrine, indicating a role for Ras in the hypertrophic effect of an alpha-adrenergic agonist.

Item Type: Paper
Uncontrolled Keywords: Animals Animals, Newborn Atrial Natriuretic Factor/genetics Cardiomegaly/*genetics Cell Division Cells, Cultured Gene Expression/drug effects/physiology Genes, fos Genes, ras/*physiology Genetic Markers Heart Ventricles/cytology Myocardium/*cytology Phenylephrine/pharmacology Rats Transfection
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > G protein
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > G protein > Ras
CSHL Authors:
Communities: CSHL labs > Powers lab
Depositing User: Matt Covey
Date: 25 January 1993
Date Deposited: 25 Feb 2014 21:16
Last Modified: 25 Feb 2014 21:16
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29525

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