The p38-MAPK inhibitor, SB203580, inhibits cardiac stress-activated protein kinases/c-Jun N-terminal kinases (SAPKs/JNKs)

SB203580 is a recognised inhibitor of p38-MAPKs. Here, we investigated the effects of SB203580 on cardiac SAPKs/JNKs. The IC50 for inhibition of p38-MAPK stimulation of MAPKAPK2 was approximately 0.07 mu M, whereas that for total SAPK/JNK activity, was 3-10 mu M. SB203580 did not inhibit immunoprecipitated JNK1 isoforms, Three peaks of SAPK/JNK activity were separated by anion exchange chromatography, eluting in the isocratic wash (44 kDa), and at 0.08 M (46 and 52 kDa) and 0.15 M NaCl (54 kDa), SB203580 (10 mu M) completely inhibited the 0.15 M NaCl activity and partially inhibited the 0.08 RI NaCl activity, Since JNK1 antibodies immunoprecipitate the 46 kDa activity, this indicates that SB203580 selectively inhibits 52 and 54 kDa SAPK/JNKs, (C) 1998 Federation of European Biochemical Societies.