DOI: 10.1083/jcb.139.1.115. A Role for the p38 Mitogen-activated Protein Kinase Pathway in Myocardial Cell Growth, Sarcomeric Organization, and Cardiac-specific Gene Expression

A Role for the p38 Mitogen-activated Protein Kinase Pathway in Myocardial Cell Growth, Sarcomeric Organization, and Cardiac-specific Gene Expression

10.1083/jcb.139.1.115

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

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 α1- 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 NH2-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 MEKK1COOH 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.

Bibliography

Zechner, D., Thuerauf, D. J., Hanford, D. S., McDonough, P. M., & Glembotski, C. C. (1997). A Role for the p38 Mitogen-activated Protein Kinase Pathway in Myocardial Cell Growth, Sarcomeric Organization, and Cardiac-specific Gene Expression. The Journal of Cell Biology, 139(1), 115â127.

Authors 5

Dietmar Zechner (first)
Donna J. Thuerauf (additional)
Deanna S. Hanford (additional)
Patrick M. McDonough (additional)
Christopher C. Glembotski (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:47 p.m.)
Deposited	2 years, 1 month ago (July 22, 2023, 5:32 a.m.)
Indexed	1 week, 1 day ago (Aug. 20, 2025, 8:26 a.m.)
Issued	27 years, 10 months ago (Oct. 6, 1997)
Published	27 years, 10 months ago (Oct. 6, 1997)
Published Online	27 years, 10 months ago (Oct. 6, 1997)
Published Print	27 years, 10 months ago (Oct. 6, 1997)

Funders 0

None

BibTeX

@article{Zechner_1997, title={A Role for the p38 Mitogen-activated Protein Kinase Pathway in Myocardial Cell Growth, Sarcomeric Organization, and Cardiac-specific Gene Expression}, volume={139}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.139.1.115}, DOI={10.1083/jcb.139.1.115}, number={1}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Zechner, Dietmar and Thuerauf, Donna J. and Hanford, Deanna S. and McDonough, Patrick M. and Glembotski, Christopher C.}, year={1997}, month=oct, pages={115–127} }

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