Heat-shock-induced activation of stress MAP kinase is regulated by threonine- and tyrosine-specific phosphatases.
In eukaryotic species from yeast to human, stress-activated protein kinases (SAPKs), members of a MAP kinase (MAPK) subfamily, regulate the transcriptional response to various environmental stress. It is poorly understood how diverse forms of stress are sensed and transmitted to SAPKs. Here, we report the heat shock regulation of the fission yeast Spc1 SAPK, a homolog of human p38 and budding yeast Hog1p. Although osmostress and oxidative stress induce strong activation of the Wis1 MAPK kinase (MEK), which activates Spc1 through Thr-171/Tyr-173 phosphorylation, activation of Wis1 upon heat shock is relatively weak and transient. However, in heat-shocked cells, Pyp1, the major tyrosine phosphatase that dephosphorylates and inactivates Spc1, is inhibited for its interaction with Spc1, which leads to strong activation of Spc1. Subsequently, Spc1 activity is rapidly attenuated by Thr-171 dephosphorylation, whereas Tyr-173 remains phosphorylated. Thr-171 dephosphorylation is compromised in a strain lacking functional type 2C serine/threonine phosphatases (PP2C), Ptc1 and Ptc3. Moreover, Ptc1 and Ptc3 can dephosphorylate Thr-171 of Spc1 both in vivo and in vitro. These observations strongly suggest that PP2C enzymes play an important role in the attenuation of Spc1 activity in heat-shocked cells. Thus, transient activation of Spc1 upon heat shock is ensured by differential regulation of threonine and tyrosine phosphorylation.
Section of Microbiology, University of California, Davis, California 95616, USA.
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Nguyen
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Shiozaki
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D018797:Cell Cycle Proteins; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal; D006358:Hot Temperature; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D010769:Phosphothreonine / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D054648:Protein Phosphatase 2; D000071636:Protein Phosphatase 2C; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological / Q000235:genetics* / Q000378:metabolism
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D010769:Phosphothreonine; D010768:Phosphoserine; D019000:Phosphotyrosine; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe; D020929:Mitogen-Activated Protein Kinase Kinases; C072068:wis1 protein, S pombe; C087358:PTC1 protein, S cerevisiae; C000607464:PTC3 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D000071636:Protein Phosphatase 2C; D017027:Protein Tyrosine Phosphatases; C097097:pyp1 protein, S pombe