G protein-coupled receptor agonist-stimulated expression of ATF3/LRF-1 and c-myc and comitogenic effects in hepatocytes do not require EGF receptor transactivation

Journal of Cellular Physiology
Laila S NilssenT Christoffersen

Abstract

Several agonists acting on G protein-coupled receptors (GPCR) enhance the mitogenic effect of epidermal growth factor (EGF) in rat hepatocytes, through mechanisms that have only partially been clarified. Results in various cells have led to the idea that a major mechanism for GPCR-mediated stimulation of cell growth is transactivation of receptor tyrosine kinases, particularly the EGF receptor (EGFR), leading to rapid phosphorylation of the EGFR and activation of downstream signaling pathways. In the present study cultured rat hepatocytes were exposed to various GPCR agonists, including vasopressin, angiotensin II (Ang.II), norepinephrine, or prostaglandin F(2 alpha) (PGF(2 alpha)). None of these agents increased the phosphorylation of the EGFR or the docking protein Shc. Furthermore, we examined the effect of the GPCR agonists on the expression of two early response genes believed to be involved in growth activation. The GPCR agonists increased the mRNA expression of c-myc, and also of activating transcription factor 3 (ATF3)/liver regeneration factor-1 (LRF-1), which is a novel finding. Finally, the selective EGFR inhibitor AG1478 did not suppress the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) or the ind...Continue Reading

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Citations

Jan 24, 2006·Molecular and Cellular Biology·Aki OkamotoYoshiro Maru
Nov 23, 2006·The Journal of Steroid Biochemistry and Molecular Biology·Bukhtiar H ShahKevin J Catt
Mar 11, 2008·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Satoru KoyanoSumio Kawata
Jan 18, 2005·Biochemical and Biophysical Research Communications·Mercedes MontielEugenio Jiménez
Sep 13, 2012·Journal of Experimental & Clinical Cancer Research : CR·Ingun Heiene TveteraasThoralf Christoffersen
Apr 17, 2012·Biochemical and Biophysical Research Communications·John ØdegårdThoralf Christoffersen
Jul 27, 2007·Journal of Cellular Physiology·Olav F DajaniThoralf Christoffersen
Jun 15, 2007·The Journal of Pharmacology and Experimental Therapeutics·Kristin MeisdalenDagny Sandnes

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