Ubiquitination of a yeast plasma membrane receptor signals its ligand-stimulated endocytosis.
Binding of alpha factor to Ste2p, a G protein-coupled plasma membrane receptor, activates a signal transduction pathway and stimulates endocytosis of the receptor-ligand complex. Ligand binding also induces ubiquitination of the Ste2p cytoplasmic tail. Protein ubiquitination is required for stimulated endocytosis of Ste2p, as internalization is 5- to 15-fold slower in ubc mutants that lack multiple ubiquitin-conjugating enzymes. In a C-terminal truncated form of Ste2p that is rapidly ubiquitinated and endocytosed in response to ligand binding, a single lysine to arginine substitution in its cytoplasmic tail eliminates both ubiquitination and internalization. Thus, ubiquitination of Ste2p itself is required for ligand-stimulated endocytosis. We propose that ubiquitination mediates degradation of receptor-ligand complexes, not via the proteasome, but by acting as a signal for endocytosis leading to subsequent degradation in the lysosome/vacuole.
Hicke
L
L
Department of Biochemistry, Biozentrum, University of Basel, Switzerland.
Riezman
H
H
D000595:Amino Acid Sequence; D001692:Biological Transport; D002268:Carboxypeptidases / Q000378:metabolism; D043402:Cathepsin A; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D006867:Hydrolases / Q000502:physiology; D008024:Ligands; D008025:Ligases / Q000235:genetics / Q000502:physiology; D008239:Lysine / Q000378:metabolism; D000072235:Mating Factor; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000378:metabolism; D009154:Mutation; D010455:Peptides / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors; D014452:Ubiquitins / Q000378:metabolism*; D014617:Vacuoles / Q000201:enzymology
D008024:Ligands; D009097:Multienzyme Complexes; D010455:Peptides; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide; D014157:Transcription Factors; D014452:Ubiquitins; D000072235:Mating Factor; D006867:Hydrolases; D002268:Carboxypeptidases; D043402:Cathepsin A; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases; D008239:Lysine