1. Academic Validation
  2. SP600125, an inhibitor of c-jun N-terminal kinase, activates CREB by a p38 MAPK-mediated pathway

SP600125, an inhibitor of c-jun N-terminal kinase, activates CREB by a p38 MAPK-mediated pathway

  • Biochem Biophys Res Commun. 2003 Aug 8;307(4):855-60. doi: 10.1016/s0006-291x(03)01287-7.
Dhara Vaishnav 1 Purevsuren Jambal Jane E-B Reusch Subbiah Pugazhenthi
Affiliations

Affiliation

  • 1 Division of Endocrinology, Department of Medicine, 4200 East Ninth Avenue, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Abstract

SP600125, an anthrapyrazolone inhibitor of c-jun N-terminal kinase (JNK), has been used to characterize the role of JNK in apoptotic pathways. In this study, we have demonstrated an additional novel anti-apoptotic action of this inhibitor in MIN6 cells, a mouse beta cell line. SP600125 induced CREB-dependent promoter activation by 2.8-fold at 20 microM, the concentration at which it inhibited c-jun-dependent promoter activation by 51%. There was a significant (P<0.01) increase in CREB phosphorylation (serine 133) at 5 min, which persisted for a period of 2h. Examination of signaling pathways upstream of CREB showed a 2.5-fold increase in the active phospho form of p38 MAPK. This finding was further confirmed by an in vitro kinase assay using ATF-2 as substrate. SB203580, an inhibitor of p38 MAPK, partially blocked SP600125-mediated activation of CREB. These observations suggest that SP600125 could be used as a small molecular weight activator of CREB.

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