Activation of cJun NH2-terminal kinase/stress-activated protein kinase by insulin
| Autor: | Uma T. Shankavaram, Bradley S. Miller, Angela C. S. Gore, David T. Kurtz, Steven A. Rosenzweig, Mark J. Horney |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
MAPK/ERK pathway
Transcription Genetic Immunoprecipitation Proto-Oncogene Proteins c-jun medicine.medical_treatment Molecular Sequence Data Biology Biochemistry Transcription (biology) medicine Animals Humans Insulin Amino Acid Sequence RNA Messenger Phosphorylation Receptor Base Sequence Sequence Homology Amino Acid Kinase JNK Mitogen-Activated Protein Kinases Molecular biology Receptor Insulin Rats Enzyme Activation Transcription preinitiation complex Calcium-Calmodulin-Dependent Protein Kinases Mitogen-Activated Protein Kinases DNA Probes |
| Zdroj: | Biochemistry. 35(26) |
| ISSN: | 0006-2960 |
| Popis: | One of insulin's many biological effects is the increased transcription of AP-1-regulated genes. cJun is the principal component of the AP-1 transcription complex, which is regulated by the newly discovered members of the MAPK superfamily referred to as cJun NH2-terminal kinases (JNKs) or stress-activated protein kinases (SAPKs). We show that insulin stimulates a dose- and time-dependent increase in JNK activity in Rat 1 fibroblasts overexpressing human insulin receptors (Rat 1 HIR cells). Using two different polyclonal anti-JNK antibodies, JNK activity was measured after immunoprecipitation from whole cell extracts by phosphorylation of GSTcJun(1-79). Peak activation occurred 15 min after insulin addition, resulting in a 2.5-fold increase in GSTcJun(1-79) phosphorylation over unstimulated controls. Maximal JNK activation correlated with the onset of AP-1 DNA binding activity. Both insulin-stimulated JNK activity and insulin-induced AP-1 transcriptional activity were found to be Ras-dependent. These data suggest that in Rat 1 cells, JNK activation may play a role in insulin-regulated AP-1 transcriptional activity leading to a mitogenic response. |
| Databáze: | OpenAIRE |
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