A comparison of the substrate specificity of MAPKAP kinase‐2 and MAPKAP kinase‐3 and their activation by cytokines and cellular stress

Abstract
MAPKAP kinase‐2 and MAPKAP kinase‐3 were both activated in response to cellular stress, interleukin‐1 and tumour necrosis factor in KB and HeLa cells, and with identical kinetics. Activation of MAPKAP kinase‐3, like MAPKAP kinase‐2, was prevented by SB 203580, a specific inhibitor of SAPK‐2, the upstream activator of MAPKAP kinase‐2. MAPKAP kinase‐3 and MAPKAP kinase‐2 phosphorylated peptide substrates with similar kinetic constants and phosphorylated the same serine residues in HSP27 at the same relative rates. These results establish that MAPKAP kinase‐3 lies ‘downstream’ of SAPK‐2 and that it is likely to have overlapping or identical substrates to MAPKAP kinase‐2 in vivo.