[Characterization of mouse apoptosis signal-regulating kinase 1]

Apoptosis Signal-regulating Kinase (ASK) 1 was identified that activated two different subgroup of MAP kinase kinase (MAPKK), SEK1 (or MKK4), and MKK3/MAPKK6 (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also known as JNK: c-Jun amino-terminal kinase) and p38 subgroup of MAP kinases, respectively. It was suggested that ASK1 contributed to cytokine-induced apoptosis in some cell lines. In this report, for further investigation about roles of ASK1 in mammal, initial characterization of mouse ASK1 was done. The mouse cDNA encoding ASK1 was isolated from the mouse kidney cDNA library and the overall amino acid sequence similarity between the mouse and the human ASK1 was 91.9%. A database search revealed that the kinase domain of ASK1 is evolutionally well-concervedover species among nematode, fly, mouse, and human. Northern blot analysis identified a 6-kb transcript of ASK1 which is expressed in the various mouse adult tissues. Immunohistochemical analysis of mouse embryos (17 days post coitum) revealed a localized expression of ASK1 in developing skin, cartilage, and bone, suggesting a possible role of ASK1 in tissue development during embryogenesis as well as cytokine-induced apoptosis.