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PMID: 1531537 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Transcriptional activation of the cardiac myosin light chain 2 and atrial natriuretic factor genes by protein kinase C in neonatal rat ventricular myocytes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 4 ·1992-02-15 ·Pages 1305-9

Shubeita HE, Martinson EA, Van Bilsen M, Chien KR, Brown JH

Abstract

A cultured myocardial cell model was used to examine the role of protein kinase C-dependent pathways in the transcriptional activation of two cardiac muscle genes [myosin light chain 2 (MLC-2) and atrial natriuretic factor (ANF)] during alpha-adrenergic receptor-mediated hypertrophy. Phorbol ester (phorbol 12-myristate 13-acetate) and the alpha-adrenergic agonist phenylephrine both activate protein kinase C (PKC) and induce 4- to 5-fold increases in the expression of MLC-2 and ANF promoter/luciferase reporter genes with little effect on Rous sarcoma virus/luciferase or minimal prolactin promoter/luciferase genes. To further assess the role of PKC in cardiac gene regulation, PKC expression vectors encoding constitutively activated PKC-alpha or PKC-beta, or a catalytically inactive PKC, were transiently cotransfected with the cardiac promoter/luciferase constructs. Cotransfection of either activated PKC-alpha or PKC-beta cDNA induces the expression of MLC-2 and ANF promoter/luciferase genes and of a reporter gene responsive to the transcription factor AP-1. The Rous sarcoma virus/luciferase and minimal prolactin promoter/luciferase genes are not concomitantly induced by cotransfectin with the PKC genes, indicating specificity of the transcriptional effect. The finding that activated PKC increases cardiac gene transcription suggests that activation of this enzyme may be a proximal signal for coregulation of two cardiac genes, MLC-2 and ANF, during the course of myocardial cell hypertrophy.

MeSH Terms
Amino Acid Sequence Animals Animals, Newborn Atrial Natriuretic Factor/genetics Blotting, Northern Cells, Cultured Gene Expression Regulation In Vitro Techniques Molecular Sequence Data Myocardium/metabolism Myosins/genetics Peptides/chemistry,metabolism Phenylephrine/pharmacology Phorbol Esters/pharmacology Phosphorylation Promoter Regions, Genetic Protein Kinase C/physiology RNA, Messenger/genetics Rats Transcription, Genetic
Chemicals
Peptides Phorbol Esters RNA, Messenger atrial natriuretic peptide, rat Phenylephrine Atrial Natriuretic Factor Protein Kinase C Myosins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Shubeita H E
Department of Pharmacology, University of California at San Diego, School of Medicine, La Jolla 92093.
Martinson E A
Van Bilsen M
Chien K R
Brown J H
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.4.1305
Published
1992-02-15
Pages
1305-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC48438
Subset
IM
Grants
NHLBI NIH HHS · HL28143 · United States
NHLBI NIH HHS · HL36139 · United States
NHLBI NIH HHS · HL45609 · United States
External Links
PubMed source DOI: 10.1073/pnas.89.4.1305 PMC Full Text View journal details
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