Ca2+-mediated activation of ERK in hepatocytes by norepinephrine and prostaglandin F2 alpha: role of calmodulin and Src kinases.
| Autor: | Melien O; Department of Pharmacology, Faculty of Medicine, University of Oslo, Box 1057 Blindern, N-0316, Oslo, Norway. oyvind.melien@c2i.net, Nilssen LS, Dajani OF, Sand KL, Iversen JG, Sandnes DL, Christoffersen T |
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| Jazyk: | angličtina |
| Zdroj: | BMC cell biology [BMC Cell Biol] 2002; Vol. 3, pp. 5. Date of Electronic Publication: 2002 Feb 20. |
| DOI: | 10.1186/1471-2121-3-5 |
| Abstrakt: | Background: 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. Results: 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. Conclusion: 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. |
| Databáze: | MEDLINE |
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