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PMID: 8089186 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mitogen-activated protein kinases mediate changes in gene expression, but not cytoskeletal organization associated with cardiac muscle cell hypertrophy.

The Journal of cell biology ·Vol. 126 ·No. 6 ·1994-09-00 ·Pages 1565-72

Thorburn J, Frost JA, Thorburn A

Abstract

Shortly after birth, cardiac myocytes lose the ability to divide, and, in adult animals, heart muscle grows by a process of cellular hypertrophy where each individual cell gets larger. We have previously shown that activated Ras protein can induce markers of the hypertrophic phenotype, including atrial natriuretic factor (ANF) expression and organization of contractile proteins, and that Ras is at least partially required for the hypertrophic effect of phenylephrine. In the present study, we examine the requirement for the mitogen-activated protein kinases (MAP kinases) in the hypertrophic response induced by phenylephrine. We find that phenylephrine treatment results in the activation of the MAP kinases and that this activity is required for transactivation of the fos, ANF, and MLH promoters. However, inhibition of MAP kinases does not prevent phenylephrine-induced organization of actin. These results suggest that the signal transduction pathways leading to different hypertrophic responses diverge upstream of the MAP kinases but possibly downstream of Ras.

MeSH Terms
Actins/ultrastructure Animals Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors,physiology Cells, Cultured Cytoskeleton/pathology Enzyme Activation Gene Expression Regulation Hypertrophy Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases Mitogens Mutation Myocardium/metabolism,pathology,ultrastructure Phenotype Phenylephrine/pharmacology Rats Tetradecanoylphorbol Acetate/pharmacology Transfection
Chemicals
Actins Mitogens Phenylephrine Calcium-Calmodulin-Dependent Protein Kinases Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases Tetradecanoylphorbol Acetate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Thorburn J
Cardiology Division, Eccles Institute of Human Genetics, University of Utah, Salt Lake City 84112.
Frost J A
Thorburn A
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46 references, click to expand
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.126.6.1565
Published
1994-09-00
Pages
1565-72
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2290965
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.126.6.1565 PMC Full Text View journal details
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