Abstract
Previous studies have shown that several agents that stimulate heptahelical G-protein coupled receptors activate the extracellular signal regulated kinases ERK1 (p44mapk) and ERK2 (p42mapk) in hepatocytes. The molecular pathways that convey their signals to ERK1/2 are only partially clarified. In the present study we have explored the role of Ca2+ and Ca2+-dependent steps leading to ERK1/2 activation induced by norepinephrine and prostaglandin (PG)F2alpha. Pretreatment of the cells with the Ca2+ chelators BAPTA-AM or EGTA, as well as the Ca2+ influx inhibitor gadolinium, resulted in a partial decrease of the ERK response. Furthermore, the calmodulin antagonists W-7, trifluoperazine, and J-8 markedly decreased ERK activation. Pretreatment with KN-93, an inhibitor of the multifunctional Ca2+/calmodulin-dependent protein kinase, had no effect on ERK activation. The Src kinase inhibitors PP1 and PP2 partially diminished the ERK responses elicited by both norepinephrine and PGF2alpha. The present data indicate that Ca2+ is involved in ERK activation induced by hormones acting on G protein-coupled receptors in hepatocytes, and suggest that calmodulin and Src kinases might play a role in these signaling pathways.
Citations
Nov 2, 2013·Lipids·Tamio YamaguchiHarold M Aukema
Jan 31, 2004·The Journal of Biological Chemistry·Justin H TurnerJohn R Raymond
Mar 11, 2005·Human Molecular Genetics·Michael D KaytorHarry T Orr
Jun 23, 2005·The Journal of Biological Chemistry·Justin H Turner, John R Raymond
Oct 28, 2005·American Journal of Physiology. Cell Physiology·Karni S MoshalSuresh C Tyagi
Jun 12, 2010·International Endodontic Journal·M C ChangJ H Jeng
Jun 3, 2011·Headache·Saurabh GuptaNancy E J Berman
Jan 23, 2009·Journal of Cellular Biochemistry·Lili ZhangLihui Wei
Aug 16, 2019·The Journal of Biological Chemistry·Cai-Hua ChenXiao-Fan Zhao
Mar 3, 2004·Journal of Neuroscience Research·Jin ZhongWei-Hua Lee
Feb 16, 2010·Journal of Lipid Research·Arion KennedyMichael McIntosh
May 1, 2008·Molecular Pharmacology·Yong LiuKim A Neve
Sep 25, 2004·Journal of Cellular Physiology·Laila S NilssenThoralf Christoffersen
Mar 20, 2010·Canadian Journal of Physiology and Pharmacology·Ting Zhang, Qingping Feng
Apr 5, 2003·The Journal of Biological Chemistry·Won K HanJoseph V Bonventre
Jan 19, 2021·Journal of Cellular Biochemistry·Wei-Chung HsuChih-Yang Huang
Jun 9, 2005·Experimental Eye Research·Lixin WangGeorge Duncan
Dec 13, 2005·Archives of Oral Biology·Olga J BakerGary A Weisman
Apr 29, 2015·Chemical Research in Toxicology·Gati Krushna PanigrahiMukul Das