PMID: 9163318Apr 15, 1997Paper

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

The Biochemical Journal
S J FullerN K Tonks

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 microM), phorbol 12-myristate 13-acetate (1 microM) 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 microM) increased myocyte area by 59% but this effect was only decreased by one-third by MKP-1 and was also par...Continue Reading

Citations

Sep 3, 2009·Pharmacology & Therapeutics·Rebecca H RitchieBarbara K Kemp-Harper
Aug 18, 2004·Biochemical and Biophysical Research Communications·Doubun HayashiIssei Komuro
Apr 6, 2000·The American Journal of Cardiology·A Clerk, P H Sugden
Apr 6, 2000·The American Journal of Cardiology·J Scheuer
May 19, 2011·Journal of Molecular and Cellular Cardiology·Joost J LeendersEsther E Creemers
Apr 3, 1999·Circulation Research·P H Sugden
Jan 28, 2005·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Marie-Josée BenoitBruce G Allen
Sep 23, 2008·Journal of Hypertension·Pietro Amedeo ModestiAlessandra Modesti
Jun 14, 2005·American Journal of Physiology. Heart and Circulatory Physiology·E Ann TallantPatricia E Gallagher
Oct 29, 1998·Biochemical and Biophysical Research Communications·M B AnderssonM A Bogoyevitch
Aug 11, 2004·International Journal of Cardiology·Ruri OhkiKazuyuki Shimada

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