A comparison of the substrate specificity of MAPKAP kinase-2 and MAPKAP kinase-3 and their activation by cytokines and cellular stress.
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.
Clifton
A D
AD
MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Scotland, UK.
Young
P R
PR
Cohen
P
P
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D016207:Cytokines / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D011817:Rabbits; D013312:Stress, Physiological; D013379:Substrate Specificity; D000099190:MAP-Kinase-Activated Kinase 2
D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C098416:MAP-kinase-activated kinase 3