MLK-3 ACTIVATES THE SAPK/JNK AND P38/RK PATHWAYS VIA SEK1 AND MKK3/6

摘要: Abstract Mixed lineage kinase-3 (MLK-3) is a 97 kDa serine/threonine kinase with multiple interaction domains, including Cdc42 binding motif, but unknown function. and the related small GTP protein Rac1 can activate SAPK/JNK p38/RK stress-responsive cascades, suggesting that MLK-3 may have role in upstream regulation of these pathways. In support this role, we demonstrate specifically pathways, has no effect on activation ERKs. Immunoprecipitated catalyzed phosphorylation SEK1 vitro, co-transfected induced MKK3 at sites required for activation, direct kinases. Furthermore, interactions between SEK MKK6 were observed co-precipitation experiments. Finally, kinase-dead mutants blocked SAPK pathway by newly identified mammalian analog Ste20, germinal center kinase, not MEKK, functions to cascades response stimuli transduced Ste20-like