Worm Breeder's Gazette 14(2): 75 (February 1, 1996)

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

Identification of a SAPK/JNK homolog and its activator MAPKKs in C. elegans

Naoki Hisamoto1, Masato Kawasaki2, Kenji Irie3, Yuichi Iino4, Kunihiro Matsumoto5

1 Department of Molecular Biology, Faculty of Science, University of Nagoya, Chikusa-ku, Nagoya 464-01, JAPAN
2 Department of Molecular Biology, Faculty of Science, University of Nagoya, Chikusa-ku, Nagoya 464-01, JAPAN
3 Department of Molecular Biology, Faculty of Science, University of Nagoya, Chikusa-ku, Nagoya 464-01, JAPAN
4 Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, JAPAN
5 Department of Molecular Biology, Faculty of Science, University of Nagoya, Chikusa-ku, Nagoya 464-01, JAPAN 

        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.  Two different cDNA clones were 
isolated.  One of them encodes a glycerol 3-phosphate dehydrogenase and 
the other encodes a protein kinase, which we designated sak-1.  sak-1 
is most similar to mammalian SAPK (69% identical).  The kinases SAPK 
and sak-1 share a TPY sequence in the activation domain, compared with 
TEY for most other known MAPKs and TGY for p38 and HOG1.  These results 
suggest that sak-1 belongs to the SAPK subfamily.
        In yeast, HOG1 is activated by the dual-specificity MAPK kinase 
(MAPKK), PBS2.  Neither sak-1 nor mammalian SAPK kinase, MKK4, rescued 
the osmosensitive phenotype of pbs2 mutants.  On the other hand, 
suppression of pbs2 was observed when sak-1 and MKK4 were coexpressed 
in yeast.  These results indicate that sak-1 is activated by PBS2 and 
MKK4 in yeast.  We used this approach to screen C. elegans cDNA library 
for the sak-1 activator MAPKKs that might rescue the pbs2 mutant in a 
sak-1 dependent manner.  Two different cDNA clones were isolated and 
both of them encode protein kinases, which we designated sek-1 and 
sek-2, respectively.  They are homologous to mammalian MAPKKs, MKK3 
and MKK4.