Insulin regulates MAP kinase phosphatase-1 induction in Hirc B cells via activation of both extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK)

• Published in: Molecular and cellular biochemistry Vol. 218; no. 1-2; pp. 131 - 138
• Main Authors: Byon, J C, Dadke, S S, Rulli, S, Kusari, A B, Kusari, J
• Format: Journal Article
• Language: English
• Published: Netherlands Springer Nature B.V 01-02-2001
• Subjects: Animals; Antineoplastic Agents, Phytogenic - pharmacology; Cell Cycle Proteins; Cells, Cultured; Dual Specificity Phosphatase 1; Enzyme Activation - drug effects; Enzyme Induction - drug effects; Enzyme Inhibitors - pharmacology; Fibroblasts - enzymology; Fibroblasts - pathology; Fibroblasts - physiology; Humans; Immediate-Early Proteins; Insulin; Insulin - metabolism; JNK Mitogen-Activated Protein Kinases; Kinases; MAP Kinase Kinase 4; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; p38 Mitogen-Activated Protein Kinases; Paclitaxel - pharmacology; Phosphoprotein Phosphatases; Protein Phosphatase 1; Protein Tyrosine Phosphatases; Protein-Serine-Threonine Kinases - metabolism; Proteins; Rats; RNA, Messenger - metabolism; Signal Transduction; Transfection
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1023/A:1007204508882

Previously, we have reported that insulin induces the expression of the dual-specificity tyrosine phosphatase Mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) and that this may represent a negative feedback mechanism to regulate insulin-stimulated MAP kinase activity. In this work, the mechanism of regulation of MKP-1 expression by insulin was examined, particularly the role of the MAP kinase superfamily. Inhibition of the ERK pathway attenuated insulin-stimulated MKP-1 mRNA expression. Expression of dominant negative molecules of the JNK pathway also abolished insulin-stimulated MKP-1 expression. However, inhibition of p38MAPK activity by SB202190 had no effect on insulin-stimulated MKP-1 induction. Simultaneous inhibition of the ERK and JNK pathways abolished the ability of insulin to stimulate MKP-1 expression, however, this combined inhibition was neither additive nor synergistic, suggesting these pathways converge to act on a common final effector. In conclusion, induction of MKP-1 mRNA expression in Hirc B cells by insulin requires activation of both the ERK and JNK pathways, but not p38MAPK.