title: PDK1 homologs activate the Pkc1-mitogen-activated protein kinase pathway in yeast.
abstract: PDK1 (phosphoinositide-dependent kinase 1) is a mammalian growth factor-regulated serine/threonine kinase. Using a genetic selection based on a mutant form of the yeast MAP kinase kinase Ste7, we isolated a gene, PKH2, encoding a structurally and functionally conserved yeast homolog of PDK1. Yeast cells lacking both PKH2 and PKH1, encoding another PDK1 homolog, were nonviable, indicating that Pkh1 and Pkh2 share an essential function. A temperature-sensitive mutant, pkh1(D398G) pkh2, was phenotypically similar to mutants defective in the Pkc1-mitogen-activated protein kinase (MAPK) pathway. Genetic epistasis 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. The Pkh2 phosphorylation site in Pkc1 (Thr-983) is part of a conserved PDK1 target motif and essential for Pkc1 function. Thus, the yeast PDK1 homologs activate Pkc1 and the Pkc1-effector MAPK pathway.
authors.affiliation: Department of Molecular Biology, Graduate School of Science, Nagoya University, and CREST, Japan Science and Technology Corporation, Chikusa-ku, Nagoya 464-8602, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Inagaki
authors.forename: T
authors.initials: T
authors.lastname: Schmelzle
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: K
authors.initials: K
authors.lastname: Irie
authors.forename: M N
authors.initials: MN
authors.lastname: Hall
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D020935:MAP Kinase Signaling System; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016296:Mutagenesis; D010766:Phosphorylation; D011493:Protein Kinase C; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C097993:Pkc1 protein, Trichoderma reesei; D064413:3-Phosphoinositide-Dependent Protein Kinases; C072075:BCK1 protein, S cerevisiae; C118385:PKH1 protein, S cerevisiae; C118386:PKH2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D020929:Mitogen-Activated Protein Kinase Kinases; C119844:STE7 protein, S cerevisiae