2. Peroxide Sensors for Fission Yeast Stress-activated MAP- kinase Pathway

3. 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

4. External Stimulus MAP KKK MAP KK MAP K ATF-2c-JUN NUCLEUS A Cell MAP Kinase Pathway in Mammalian Cells Internal Stimulus

5. Hog1p MAP kinase Ssk1pSsk2p/Ssk22p P Sln1p YD1P P Stress Response Pathway in S. cerevisiae Finding Parallels Sty1p Mcs4pWak1p P Stress Response in S. pombe

6. Mcs4p Sty1p P Heavy Metal Poisoning Superoxide ions (Parquat) Mak2p/Mak3p?

7. Strains Used Table 1

8. Mcs4p is Required for Activation of Sty1p MAPK Specifically in Response to Peroxide Stress Fig. 01

9. Sequence Alignment of Mak1p, Mak2p, & Mak3p Fig. 03

10. Identification of Three Non-essential Histidine kinases in Fission Yeast Fig. 02 Sr/Thr domain PAS/PAC domain His kinase domain Response regulator domain

11. Identification of Three Non-essential Histidine kinases in Fission Yeast Fig. 02

12. Mak2p & Mak3p are Required for Sty1p Activation in Response to Peroxide Stress Fig. 04

13. H2O2H2O2 Sty1p ATF1 gpx1 Pyp2 H2O2H2O2 Sty1p PAP1p or Prp1p ctt Bifurcation in Pathways Following Oxidative Stress

14. Mak2p & Mak3p Control Atf1p-dependent Gene Transcription in Response to Peroxide Stress Fig. 05

15. Mak2p & Mak3p Protect Cells Against Peroxide Attack Fig. 06

16. 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.

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

18. Thanks!