PDK1 Homologs Activate the Pkc1-Mitogen-Activated Protein Kinase Pathway in Yeast

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Molecular and Cellular Biology, December 1999, p. 8344-8352, Vol. 19, No. 12
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

PDK1 Homologs Activate the Pkc1-Mitogen-Activated Protein Kinase Pathway in Yeast

Maiko Inagaki,¹ Tobias Schmelzle,² Kyoko Yamaguchi,¹ Kenji Irie,¹ Michael N. Hall,² and Kunihiro Matsumoto¹^,^*

Department of Molecular Biology, Graduate School of Science, Nagoya University, and CREST, Japan Science and Technology Corporation, Chikusa-ku, Nagoya 464-8602, Japan,¹ and Department of Biochemistry, Biozentrum, University of Basel, CH-4056 Basel, Switzerland²

Received 19 July 1999/Accepted 1 September 1999

PDK1 (phosphoinositide-dependent kinase 1) is a mammalian growth factor-regulated serine/threonine kinase. Using a geneticselection based on a mutant form of the yeast MAP kinase kinaseSte7, we isolated a gene, PKH2, encoding a structurally and functionallyconserved yeast homolog of PDK1. Yeast cells lacking both PKH2and PKH1, encoding another PDK1 homolog, were nonviable, indicatingthat Pkh1 and Pkh2 share an essential function. A temperature-sensitivemutant, pkh1^D398G pkh2, was phenotypically similar to mutants defective in thePkc1-mitogen-activated protein kinase (MAPK) pathway. Geneticepistasis analyses, the phosphorylation of Pkc1 by Pkh2 in vitro,and reduced Pkc1 activity in the pkh1^D398G pkh2 mutant indicate that Pkh functions upstream of Pkc1. ThePkh2 phosphorylation site in Pkc1 (Thr-983) is part of a conservedPDK1 target motif and essential for Pkc1 function. Thus, the yeastPDK1 homologs activate Pkc1 and the Pkc1-effector MAPKpathway.

^* Corresponding author. Mailing address: Department of Molecular Biology, Graduate School of Science, Nagoya University, Chikusa-ku,Nagoya 464-8602, Japan. Phone: 81-52-789-3000. Fax: 81-52-789-2589or 81-52-789-3001. E-mail: g44177a{at}nucc.cc.nagoya-u.ac.jp.

Molecular and Cellular Biology, December 1999, p. 8344-8352, Vol. 19, No. 12
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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