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Molecular and Cellular Biology, August 2003, p. 5132-5142, Vol. 23, No. 15
0270-7306/03/$08.00+0 DOI: 10.1128/MCB.23.15.5132-5142.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Identification of Cdc37 as a Novel Regulator of the Stress-Responsive Mitogen-Activated Protein Kinase
Hisashi Tatebe and Kazuhiro Shiozaki*
Section of Microbiology, University of California, Davis, California 95616
Received 13 February 2003/
Returned for modification 8 April 2003/
Accepted 5 May 2003
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.
* Corresponding author. Mailing address: Section of Microbiology, University of California, Davis, CA 95616. Phone: (530) 752-3628. Fax: (530) 752-9014. E-mail:
kshiozaki{at}ucdavis.edu.
Molecular and Cellular Biology, August 2003, p. 5132-5142, Vol. 23, No. 15
0022-538X/03/$08.00+0 DOI: 10.1128/MCB.23.15.5132-5142.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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