title: A novel protein kinase homolog essential for protein sorting to the yeast lysosome-like vacuole.
abstract: The VPS15 gene encodes a novel protein kinase homolog that is essential for the efficient delivery of soluble hydrolases to the yeast vacuole. Point mutations altering highly conserved residues within the Vps15p kinase domain result in the secretion of multiple vacuolar proteases. In addition, the in vivo phosphorylation of Vps15p is defective in these kinase domain mutants, suggesting that Vps15p may regulate specific protein phosphorylation reactions required for protein sorting to the yeast vacuole. Subcellular fractionation studies further demonstrate that the 1455 amino acid Vps15p is peripherally associated with the cytoplasmic face of a late Golgi or vesicle compartment. This association may be mediated by myristate as Vps15p contains a consensus signal for N-terminal myristoylation. We propose that protein phosphorylation may act as a molecular "switch" within intracellular protein sorting pathways by actively diverting proteins from a default transit pathway (e.g., secretion) to an alternative pathway (e.g., to the vacuole).
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena 91125.
authors.forename: P K
authors.initials: PK
authors.lastname: Herman
authors.forename: J H
authors.initials: JH
authors.lastname: Stack
authors.forename: J A
authors.initials: JA
authors.lastname: DeModena
authors.forename: S D
authors.initials: SD
authors.lastname: Emr
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D005800:Genes, Fungal; D006867:Hydrolases / Q000378:metabolism*; D007700:Kinetics; D008247:Lysosomes / Q000201:enzymology; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000648:ultrastructure; D012689:Sequence Homology, Nucleic Acid; D014617:Vacuoles / Q000201:enzymology* / Q000648:ultrastructure
chemical_list: D011494:Protein Kinases; D006867:Hydrolases