Mitogen-activated protein kinase (MAPK) cascades are activated in response to various extracelluler stimuli, including growth factors and environmental stresses. Mammalian ASK1 belongs to MAP kinase kinase kinase superfamily. ASK1 activates two different subgroups of MAP kinase kinase, SEK1 (MKK4) and MKK3/MKK6, which in turn activate SAPK/JNK (stress-activated protein kinase/ c-Jun amino-terminal kinase) and
p38 subgroups of MAPK family, respectively. ASK1 is proposed to play an essential role in the mechanism of stress- and cytokine-induced apoptosis in mammals. We have identified a C.elegans homolog of ASK1, named
ask-1, from the C.elegans genome database. We have isolated the
ask-1 cDNA clone by PCR. Sequence analysis revealed that it encodes a 1397 amino acid protein with 63% identity in the kinase domain and 40% identity in the full length to the ASK1 protein. In total RNA isolated from mixed stage population of wild-type,
ask-1 cDNA probes recognized a single band of approximately 5 kb on northern blots. To determine the
ask-1 expression pattern, we have generated transgenic lines carrying GFP driven by the
ask-1 promoter (ASK-1 ::GFP) in N2. ASK-1::GFP was strongly expressed in intestine, epidermis, excretory canal and some neurons. These expressions could be detected from 1.5-fold stages to adulthood. To predict the phenotype resulting from loss-of-function of
ask-1, we used RNA-mediated interference with gene function (RNAi). We injected sense RNA to a strain expressing GFP in neurons (obtained from T. Ishihara and S. Takagi). In most of F1 hermaphrodites from injected worms, migration of posterior lateral ganglions was disrupted. Furthermore, an excess cell body-like structure was observed around the posterior lateral ganglions in 30% of the progeny of the animals. These results suggest that
ask-1 may participate in the proper cell migration.