Glucagon-induced expression of the MAP kinase phosphatase MKP-1 in rat hepatocytes.
OBJECTIVE
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 micromol/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.
Schliess
F
F
Klinik für Gastroenterologie und Infektiologie, Medizinische Einrichtungen der Heinrich-Heine Universität, Düsseldorf, Germany. freimut.schliess@uni-duesseldorf.de
Kurz
A K
AK
Häussinger
D
D
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D054638:Dual Specificity Phosphatase 1; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases; D010766:Phosphorylation; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013873:Thionucleotides / Q000494:pharmacology
D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D004815:Epidermal Growth Factor; D005934:Glucagon; D000242:Cyclic AMP; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases