Ca²⁺-mediated activation of ERK in hepatocytes by norepinephrine and prostaglandin F_2α: role of calmodulin and src kinases

• Main Authors: Sand Kristin, Dajani Olav F, Nilssen Laila S, Melien Øyvind, Iversen Jens-Gustav, Sandnes Dagny L, Christoffersen Thoralf
• Format: Article
• Language: English
• Published: BMC 2002-02-01
• Series: BMC Cell Biology
• Online Access: http://www.biomedcentral.com/1471-2121/3/5
• ISSN: 1471-2121

<p>Abstract</p> <p>Background</p> <p>Previous studies have shown that several agents that stimulate heptahelical G-protein coupled receptors activate the extracellular signal regulated kinases ERK1 (p44^mapk) and ERK2 (p42^mapk) 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)F_2α.</p> <p>Results</p> <p>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 PGF_2α.</p> <p>Conclusion</p> <p>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.</p>