V. Buck et al., Peroxide sensors for the fission yeast stress-activated mitogen-activated protein kinase pathway, MOL BIOL CE, 12(2), 2001, pp. 407-419
The Schizosaccharomyces pombe stress-activated Sty1p/Spc1p mitogen-activate
d protein (MAP) kinase regulates gene expression through the Atf1p and Pap1
p transcription factors, homologs of human ATF2 and c-jun, respectively. Mc
s4p, a response regulator protein, acts upstream of Sty1p by binding the Wa
k1p/Wis4p MAP kinase kinase kinase. We show that phosphorylation. of Mcs4p
on a conserved aspartic acid residue is required for activation of Sty1p on
ly in response to peroxide stress. Mcs4p acts in a conserved phospho-relay
system initiated by two PAS/PAC domain-containing histidine kinases, Mak2p
and Mak3p. In the absence of Mak2p or Mak3p, Sty1p fails to phosphorylate t
he Atf1p transcription factor or induce Atf1p-dependent gene expression. As
a consequence, cells lacking Mak2p and Mak3p are sensitive to peroxide att
ack in the absence of Prr1p, a distinct response regulator protein that fun
ctions in association with Pap1p. The Mak1p histidine kinase, which also co
ntains PAS/PAC repeats, does not regulate Sty1p or Atf1p but is partially r
equired for Pap1p- and Prr1p-dependent transcription. We conclude that the
transcriptional response to free radical attack is initiated by at least tw
o distinct phospho-relay pathways in fission yeast.