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

kinase-2 and MAduanyu1529P 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 MAduanyu1529P kinase-3, like MAduanyu1529P kinase-2, was prevented by SB 203580, a specific inhibitor of SAPK-2, the upstream activator of MAduanyu1529P kinase-2. MAduanyu1529P kinase-3 and MAduanyu1529P 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 MAduanyu1529P kinase-3 lies 'downstream' of SAPK-2 and that it is likely to have overlapping or identical substrates to MAduanyu1529P kinase-2 in vivo.

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