THE FISSION YEAST MITOTIC REGULATOR WIN1(+) ENCODES AN MAP KINASE KINASE KINASE THAT PHOSPHORYLATES AND ACTIVATES WIS1 MAP KINASE KINASE INRESPONSE TO HIGH OSMOLARITY
I. Samejima et al., THE FISSION YEAST MITOTIC REGULATOR WIN1(+) ENCODES AN MAP KINASE KINASE KINASE THAT PHOSPHORYLATES AND ACTIVATES WIS1 MAP KINASE KINASE INRESPONSE TO HIGH OSMOLARITY, Molecular biology of the cell, 9(8), 1998, pp. 2325-2335
The Schizosaccharomyces pombe win1-1 mutant has a defect in the G2-M t
ransition of the cell cycle. Although the defect is suppressed by wis1
(+) and wis4(+), which are components of a stress-activated MAP kinase
pathway that links stress response and cell cycle control, the molecu
lar identity of Win1 has not been known. We show here that win1(+) enc
odes a polypeptide of 1436 residues with an apparent molecular size of
180 kDa and demonstrate that Win1 is a MAP kinase kinase kinase that
phosphorylates and activates Wis1. Despite extensive similarities betw
een Win1 and Wis4, the two MAP kinase kinase kinases have distinct fun
ctions. Wis4 is able to compensate for loss of Win1 only under unstres
sed conditions to maintain basal Wis1 activity, but it fails to suppre
ss the osmo-signaling defect conferred by win1 mutations. The win1-1 m
utation is a spontaneous duplication of 16 nucleotides, which leads to
a frameshift and production of a truncated protein lacking the kinase
domain. We discuss the cell cycle phenotype of the win1-1 cdc25-22 we
e1-50 mutant and its suppression by wis genes.