MAP kinase kinase kinase (MAPKKK)-dependent and -independent activation of Sty1 stress MAPK in fission yeast.
In fission yeast, the Sty1/Spc1/Phh1 mitogen-activated protein kinase (MAPK) pathway is known to be involved in multiple-stress responses. It is currently thought that the Sty1 MAPK cascade is mediated by histidine kinases and phosphorelay proteins in response to oxidative stress signals. However, studies of the exact transduction mechanism of multiple-stress responses are lacking. Thus, in response to various stimuli, we monitored the Sty1 MAPK pathway through the downstream transcription factor Atf1 in living cells using a highly sensitive luciferase reporter gene. Surprisingly, in cadmium and low glucose (LG) medium, Atf1 activation was observed even in the absence of all of the four fission yeast MAPK kinase kinases (MAPKKKs); whereas in osmotic stress, Atf1 activation was abolished. Thus, the osmotic stress likely mediates the MAPK activation via MAPKKKs, whereas a cadmium or LG condition activates the MAPK in a MAPKKK-independent manner. On the other hand, knockout of tyrosine phosphatase gene pyp1(+) abolished the Atf1 response to cadmium and LG, but not to osmotic stress, suggesting that Pyp1 is a sensor for cadmium and LG.
Zhou
Xin
X
From the Division of Molecular Pharmacology and Pharmacogenomics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kusunoki-cho 6-5-1, Chuo-ku, Kobe 650-0017, Japan.
Ma
Yan
Y
From the Division of Molecular Pharmacology and Pharmacogenomics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kusunoki-cho 6-5-1, Chuo-ku, Kobe 650-0017, Japan.
Sugiura
Reiko
R
Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, Kowakae 3-4-1, Higashi-Osaka, 577-8502, Japan.
Kobayashi
Daiki
D
From the Division of Molecular Pharmacology and Pharmacogenomics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kusunoki-cho 6-5-1, Chuo-ku, Kobe 650-0017, Japan.
Suzuki
Masahiro
M
From the Division of Molecular Pharmacology and Pharmacogenomics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kusunoki-cho 6-5-1, Chuo-ku, Kobe 650-0017, Japan.
Deng
Lu
L
From the Division of Molecular Pharmacology and Pharmacogenomics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kusunoki-cho 6-5-1, Chuo-ku, Kobe 650-0017, Japan.
Kuno
Takayoshi
T
From the Division of Molecular Pharmacology and Pharmacogenomics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kusunoki-cho 6-5-1, Chuo-ku, Kobe 650-0017, Japan. Electronic address: tkuno@med.kobe-u.ac.jp.
D051697:Activating Transcription Factor 1 / Q000235:genetics / Q000378:metabolism; D002104:Cadmium / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009997:Osmotic Pressure / Q000187:drug effects / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000201:enzymology*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D013549:Sweetening Agents / Q000378:metabolism / Q000494:pharmacology
D051697:Activating Transcription Factor 1; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D029702:Schizosaccharomyces pombe Proteins; D013549:Sweetening Agents; C106740:atf1 protein, S pombe; D002104:Cadmium; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe; D020930:MAP Kinase Kinase Kinases; D017027:Protein Tyrosine Phosphatases; C097097:pyp1 protein, S pombe; D005947:Glucose