Stress-activated protein kinase/ c-Jun NH2-terminal kinase (SAPK/JNK) and
p38 belong to a subgroup of the mitogen-activated protein kinase (MAPK) superfamily and are activated in response to a variety of stresses in mammalian cells. Mammalian SAPK and
p38 can substitute for HOG1 function, the yeast MAPK homolog involved in the osmoregulation. To identify homologs of SAPK or
p38 in C. elegans, we constructed a cDNA expression library from C. elegans and screened it for the complementation of
hog1 mutants. One of the cDNA clone encodes a protein kinase, which we designated
sak-1. Sak-1 is most similar to mammalian SAPK. In yeast, HOG1 is activated by the dual-specificity MAPK kinase (MAPKK), PBS2. To isolate the
sak-1 activator MAPKKs in C.elegans, we screened C. elegans cDNA library that can rescue the
pbs2 mutant in a
sak-1 dependent manner. Two different cDNA clones were isolated and both of them encode MAPKK-like protein kinases, designated
sek-1 and
sek-2 respectively. Sek-1 can activate both Sak-1 and C.elegans
p38 homolog Cep-38, while Sek-2 can only activate Sak-1 when expressed in yeast. The data suggest that Sek-1 and Sek-2 have different substrate specifity. We have analyzed the spatial and temporal pattern of
sak-1 and
sek-2 expression in stable transgenic lines expressing
sak-1/GFP and
sek-2/GFP fusions, respectively. Both
sak-1/GFP and
sek-2/GFP expressed in nerve ring, ventral and dorsal cords, BDU, SDQ, ALM, CAN, HSN, PDE, PVD, AVM and many unidentified neuronal cells. These expressions can detect from the late embryonic stages and persists into adulthood. No expression was detected in pharynx, muscles, gonads, and hypodermis. These data suggest that
sak-1 and
sek-2 may be the components of a novel MAP kinase cascade that may function in neurons.