Peroxide Sensors for Fission Yeast Stressactivated MAPkinase Pathway

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Peroxide Sensors for Fission Yeast
Stress-activated MAP-kinase Pathway
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V. Buck, J. Quinn, T.S. Pino, H. Martin, J.
Saldanha, K. Makino, B. A. Morgan, J. B.A.
Millar

• Molecular Biology of the Cell, 12, 2001
• Ashim Malhotra
• November 04, 2003

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MAP Kinase Pathway in Mammalian Cells
External Stimulus
MAP KKK
MAP KK
MAP K
Internal Stimulus
ATF-2
c-JUN
NUCLEUS
A Cell
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Finding Parallels
Sln1p
P
YD1P
P
Hog1p MAP kinase
Ssk1p
Ssk2p/Ssk22p
Stress Response Pathway in S. cerevisiae
P
Mcs4p
Wak1p
Sty1p
Stress Response in S. pombe
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Heavy Metal Poisoning
Superoxide ions
(Parquat)
Mak2p/Mak3p?
P
Mcs4p
Mcs4p
Sty1p
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Strains Used
Table 1
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Mcs4p is Required for Activation of Sty1p MAPK
Specifically in Response to Peroxide Stress
Fig. 01
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Sequence Alignment of Mak1p, Mak2p, Mak3p
Fig. 03
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Identification of Three Non-essential Histidine
kinases in Fission Yeast
PAS/PAC domain
His kinase domain
Response regulator domain
Sr/Thr domain
Fig. 02
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Identification of Three Non-essential Histidine
kinases in Fission Yeast
Fig. 02
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Mak2p Mak3p are Required for Sty1p Activation
in Response to Peroxide Stress
Fig. 04
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Bifurcation in Pathways Following Oxidative Stress
H2O2
H2O2
Sty1p
Sty1p
PAP1p or Prp1p
ATF1
gpx1
Pyp2
ctt
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Mak2p Mak3p Control Atf1p-dependent Gene
Transcription in Response to Peroxide Stress
Fig. 05
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Mak2p Mak3p Protect Cells Against Peroxide
Attack
Fig. 06
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Conclusions

• Mcs4p acts in a 2 component system, that
  specifically senses peroxide stress.
• Deletion of either Mak2p or Mak3p Histidine
  kinase, but not Mak1p, prevents phosphorylation
  of Sty1p in response to peroxide stress.
• Mak1p is partially required for catlase induction
  in response to peroxide stress.
• Mak1p, Mak2p Mak3p were the first proteins
  discovered that had 2 separate kinase domains of
  apparently distinct specificity.

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Regulation of the Sty1p MAP kinase Cascade by a
Two-Component Peroxide Receptor
Fig. 07
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