Abstract
Background & Aims: Glucagon exerts pleiotropic effects on liver function, but the underlying signal transduction is incompletely understood. We investigated the effect of glucagon on the mitogen-activated protein (MAP) kinase phosphatase MKP-1 expression. Methods: The effect of glucagon on MKP-1 expression was studied in cultured rat hepatocytes. Results: Glucagon (10–100 nmol/L) and 8-CPT-cAMP (10 or 50 μmol/L) stimulated in rat hepatocytes the expression of MKP-1 messenger RNA and protein, which became maximal within 30 minutes and declined to nearly basal levels after 60 minutes. MKP-1 induction by glucagon was sensitive to inhibition of adenylate cyclase and protein kinase A. The protein kinases G and C, Ca 2+, MAP kinases, reactive oxygen intermediates, and cellular dehydration were not involved in the glucagon-induced signaling to MKP-1. MKP-1 expression correlated with glucagon-induced antagonization of MAP kinase phosphorylation by epidermal growth factor in hepatocytes. Conclusions: The MKP-1 response to glucagon produces an additional level of interaction with MAP kinase–dependent processes, which may contribute to the regulation of liver function by glucagon or other cAMP-elevating agents. GASTROENTEROLOGY 2000;118:929-936
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