The protein kinase C inhibitor, Ro-31-7459, is a potent activator of ERK and JNK MAP kinases in HUVECs and yet inhibits cyclic AMP-stimulated SOCS-3 gene induction through inactivation of the transcription factor c-Jun.

Cellular Signalling
Jolanta WiejakStephen J Yarwood

Abstract

Induction of the suppressor of cytokine signalling 3 (SOCS-3) gene is vital to the normal control of inflammatory signalling. In order to understand these processes we investigated the role of the proto-oncogene component of the AP-1 transcription factor complex, c-Jun, in the regulation of SOCS-3 gene induction. We found that cyclic AMP stimulation of HUVECs promoted phosphorylation and activation of JNK MAP kinase and its substrate c-Jun. The JNK responsive element of the human SOCS-3 promoter mapped to a putative AP-1 site within 1000bp of the transcription start site. The PKC inhibitors, GF-109203X, Gö-6983 and Ro-317549, were all found to inhibit AP-1 transcriptional activity, transcriptional activation of this minimal SOCS-3 promoter and SOCS-3 gene induction in HUVECs. Interestingly, Ro-317549 treatment was also found to promote PKC-dependent activation of ERK and JNK MAP kinases and promote JNK-dependent hyper-phosphorylation of c-Jun, whereas GF-109203X and Gö-6983 had little effect. Despite this, all three PKC inhibitors were found to be effective inhibitors of c-Jun DNA-binding activity. The JNK-dependent hyper-phosphorylation of c-Jun in response to Ro-317549 treatment of HUVECs does therefore not interfere with its...Continue Reading

References

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Feb 13, 2009·British Journal of Pharmacology·Gillian BorlandStephen J Yarwood
Apr 22, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Taiga TamiyaAkihiko Yoshimura
Apr 27, 2011·Immunology and Cell Biology·Ben A CrokerAndrew W Roberts
Dec 8, 2011·British Journal of Pharmacology·Euan ParnellStephen J Yarwood

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Citations

Jul 7, 2007·Methods in Cell Biology·Tanmay P LeleDonald E Ingber
Jul 24, 2013·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Feng LiShimin Zhao

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Methods Mentioned

BETA
ubiquitination
transfections
transfection
Assay
scraping
ELISA
PMA

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