| Title: | The conserved Pkh-Ypk kinase cascade is required for endocytosis in yeast |
| Author(s): | deHart AK; Schnell JD; Allen DA; Hicke L; |
| Address: | "Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208, USA" |
| ISSN/ISBN: | 0021-9525 (Print) 1540-8140 (Electronic) 0021-9525 (Linking) |
| Abstract: | "Internalization of activated signaling receptors by endocytosis is one way cells downregulate extracellular signals. Like many signaling receptors, the yeast alpha-factor pheromone receptor is downregulated by hyperphosphorylation, ubiquitination, and subsequent internalization and degradation in the lysosome-like vacuole. In a screen to detect proteins involved in ubiquitin-dependent receptor internalization, we identified the sphingoid base-regulated serine-threonine kinase Ypk1. Ypk1 is a homologue of the mammalian serum- and glucocorticoid-induced kinase, SGK, which can substitute for Ypk1 function in yeast. The kinase activity of Ypk1 is required for receptor endocytosis because mutations in two residues important for its catalytic activity cause a severe defect in alpha-factor internalization. Ypk1 is required for both receptor-mediated and fluid-phase endocytosis, and is not necessary for receptor phosphorylation or ubiquitination. Ypk1 itself is phosphorylated by Pkh kinases, homologues of mammalian PDK1. The threonine in Ypk1 that is phosphorylated by Pkh1 is required for efficient endocytosis, and pkh mutant cells are defective in alpha-factor internalization and fluid-phase endocytosis. These observations demonstrate that Ypk1 acts downstream of the Pkh kinases to control endocytosis by phosphorylating components of the endocytic machinery" |
| Keywords: | "3-Phosphoinositide-Dependent Protein Kinases Cloning, Molecular Conserved Sequence *Endocytosis Evolution, Molecular Glycogen Synthase Kinase 3 Mating Factor Mutation Peptides/genetics/metabolism Phosphorylation Protein Kinases/metabolism Protein Serine-T;" |
| Notes: | "MedlinedeHart, Amy K A Schnell, Joshua D Allen, Damian A Hicke, Linda eng R01 DK053257/DK/NIDDK NIH HHS/ R01 DK53257/DK/NIDDK NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 2002/01/25 J Cell Biol. 2002 Jan 21; 156(2):241-8. doi: 10.1083/jcb.200107135. Epub 2002 Jan 21" |
