Identification of Cdc37 as a novel regulator of the stress-responsive mitogen-activated protein kinase.
Eukaryotic cells utilize multiple mitogen-activated protein kinases (MAPKs) to transmit various extracellular stimuli to the nucleus. A subfamily of MAPKs that mediates environmental stress stimuli is also called stress-activated protein kinase (SAPK), which has crucial roles in cellular survival under stress conditions as well as inflammatory responses. Here we report that Cdc37, an evolutionarily conserved kinase-specific chaperone, is a positive regulator of Spc1 SAPK in the fission yeast Schizosaccharomyces pombe. Through a genetic screen, we have identified cdc37 as a mutation that compromises signaling through Spc1 SAPK. The Cdc37 protein physically interacts with Spc1, and the cdc37 mutation affects both the cellular level of the Spc1 protein and stress-induced Spc1 phosphorylation by Wis1 MAPK kinase (MAPKK). Consistently, expression of the stress response genes regulated by the Spc1 pathway is compromised in cdc37 mutant cells. On the other hand, a mutation in Hsp90, which often cooperates with Cdc37 in chaperoning protein kinases, does not affect Spc1 SAPK. These results suggest that Spc1 SAPK is a novel client protein for the Cdc37 chaperone, and the Cdc37 function is important to maintain the stability of the Spc1 protein and to facilitate stress signaling from Wis1 MAPKK to Spc1 SAPK.
Tatebe
Hisashi
H
Section of Microbiology, University of California, Davis, CA 95616, USA.
Shiozaki
Kazuhiro
K
D000483:Alleles; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000502:physiology*; D002470:Cell Survival; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D015151:Immunoblotting; D007249:Inflammation; D020935:MAP Kinase Signaling System; D008856:Microscopy, Fluorescence; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D018832:Molecular Chaperones / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D018384:Oxidative Stress; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013696:Temperature; D013997:Time Factors
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D029702:Schizosaccharomyces pombe Proteins; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe; D020929:Mitogen-Activated Protein Kinase Kinases; C072068:wis1 protein, S pombe