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 inhibitio n of p38-MAPK stimulation of MAPKAPK2 was approximately 0.07 mu M, whe reas that for total SAPK/JNK activity, was 3-10 mu M. SB203580 did not inhibit immunoprecipitated JNK1 isoforms, Three peaks of SAPK/JNK act ivity 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 act ivity and partially inhibited the 0.08 RI NaCl activity, Since JNK1 an tibodies immunoprecipitate the 46 kDa activity, this indicates that SB 203580 selectively inhibits 52 and 54 kDa SAPK/JNKs, (C) 1998 Federati on of European Biochemical Societies.