Activation of cJun NH2-terminal kinase/stress-activated protein kinase by insulin

Bradley S. Miller, Uma T. Shankavaram, Mark J. Homey, Angela C S Gore, David T. Kurtz, Steven A. Rosenzweig

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

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 c Jun 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.

Original languageEnglish (US)
Pages (from-to)8769-8775
Number of pages7
JournalBiochemistry
Volume35
Issue number26
DOIs
StatePublished - 1996

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