A function for monoubiquitination in the internalization of a G protein-coupled receptor.
Modification of an S. cerevisiae G protein-coupled receptor with ubiquitin is required for its ligand-stimulated internalization. We now demonstrate that monoubiquitination on a single lysine residue is sufficient to signal receptor internalization, a modification distinct from that required for proteasome recognition. Formation of a polyubiquitin chain is not necessary, as demonstrated by the ability of mutant ubiquitins that lack lysine residues to serve as efficient internalization signals. Fusion of ubiquitin in-frame to a receptor that lacks cytoplasmic tail lysines also promotes rapid receptor internalization, indicating that ubiquitin itself and not a specific type of linkage to the receptor acts as an internalization signal. Thus, we have defined a cellular function for monoubiquitination in alpha-factor receptor endocytosis.
Terrell
J
J
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208-3500, USA.
Shih
S
S
Dunn
R
R
Hicke
L
L
D000818:Animals; D002455:Cell Division / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D016296:Mutagenesis / Q000502:physiology; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000502:physiology; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
D051964:Receptors, Mating Factor; D018000:Receptors, Peptide; D014157:Transcription Factors; D014452:Ubiquitins; D019204:GTP-Binding Proteins; D008239:Lysine