A Novel Interaction between Apoptosis Signal-Regulating Kinase 1 (ASK1) and c-Jun N-Terminal Kinase (JNK)

Abstract

Mitogen-activated protein kinases (MAPKs) are a family of intracellular serine/threonine protein kinases that transmit extracellular stimuli to the machinery that controls fundamental cellular processes like growth, gene expression, differentiation, and apoptosis. MAPKs function sequentially in a three-tiered kinase module in which an upstream MAPK kinase kinase (MAPKKK) activates a MAPK kinase (MAPKK), which in turn activates the downstream MAPK. We recently discovered a previously unknown interaction between ASK1, the MAPK kinase kinase (MAPKKK) in the JNK cascade, and JNK3, the downstream MAPK. These novel interactions (ASK1 and JNKs) were studied using biochemical assays such as pull-down, kinase assay and western blotting. Our findings confirm the interactions between ASK1 and the JNK subfamilies (JNK1,2 and 3), with JNK3 isoforms binding ASK1 more strongly than the other two subfamilies. This resulted in the identification of a major ASK1 binding site in JNK3. The findings of this study will contribute to a better understanding of the assembly and function of multi-component MAPK complexes.