Mitogen-activated protein kinase phosphatase 1 inhibits the stimulation of gene expression by hypertrophic agonists in cardiac myocytes

Fuller, S. J., Davies, E. L., Gillespie Brown, J., Sun, H., Tonks, N. K. (April 1997) Mitogen-activated protein kinase phosphatase 1 inhibits the stimulation of gene expression by hypertrophic agonists in cardiac myocytes. Biochemical Journal, 323. pp. 313-319. ISSN 0264-6021

URL: http://www.ncbi.nlm.nih.gov/pubmed/9163318

Abstract

The effect of constitutive expression of mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) on gene expression in response to hypertrophic agonists was examined in cultured neonatal rat ventricular myocytes. Luciferase (LUX) reporter genes linked to promoters for atrial natriuretic factor, ventricular myosin light chain 2, beta-myosin heavy chain, skeletal muscle alpha-actin (SkM alpha-actin) and serum response element-regulated c-fos (c-fos-SRE) were transfected into cardiomyocytes. Phenylephrine (PE; 10 mu M), phorbol 12-myristate 13-acetate (1 mu M) and endothelin 1 (10 nM) stimulated the expression of these various reporter genes by 2.5-20-fold. MKP-1 inhibited these effects by 60-85%. In contrast, MKP-1 had no effect on the expression of a constitutively active Rous sarcoma virus-LUX reporter gene. A catalytically inactive mutant MKP-1CS (cysteine-->serine mutation) and the broad-specificity protein tyrosine phosphatase 1B (PTP-1B) had no significant effect on any reporter gene tested. MKP-1 had much less effect on the morphological features accompanying agonist-induced cardiac hypertrophy. PE(10 mu M) increased myocyte area by 59% but this effect was only decreased by one-third by MKP-1 and was also partly decreased (by 25%) by expression of PTP-1B. PE also altered cell shape but this was unaffected by MKP-1. There was also no clear effect of MKP-1 on the organization of the contractile apparatus into sarcomeric structures in the presence of 10 mu M PE. We conclude that the transcriptional responses accompanying cardiac myocyte hypertrophy are dependent on an MKP-1-sensitive step, presumably the activation of one or members of the MAPK family, but that cell size, shape and myofibrillar organization are much less sensitive to inhibition by MKP-1.

Item Type: Paper
Uncontrolled Keywords: MYOSIN LIGHT CHAIN-2 ATRIAL-NATRIURETIC-FACTOR RAT MYOCARDIAL-CELLS IMMEDIATE-EARLY GENE ALPHA-ADRENERGIC STIMULATION PHORBOL ESTER STIMULATION MAP KINASE VENTRICULAR MYOCYTES SIGNAL-TRANSDUCTION TYROSINE KINASE
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > Mitogen-activated protein kinase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > protein phosphatase
CSHL Authors:
Communities: CSHL labs > Tonks lab
Depositing User: Matt Covey
Date: April 1997
Date Deposited: 18 Dec 2013 16:04
Last Modified: 18 Dec 2013 16:04
PMCID: PMC1218321
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29045

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