Ubiquitination of a Yeast Plasma Membrane Receptor Signals Its Ligand-Stimulated Endocytosis

Cell. 1996 Jan 26;84(2):277-87. doi: 10.1016/s0092-8674(00)80982-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Biological Transport
  • Carboxypeptidases / metabolism
  • Cathepsin A
  • Cysteine Endopeptidases / metabolism
  • Endocytosis / physiology*
  • Hydrolases / physiology
  • Ligands
  • Ligases / genetics
  • Ligases / physiology
  • Lysine / metabolism
  • Mating Factor
  • Molecular Sequence Data
  • Molecular Weight
  • Multienzyme Complexes / metabolism
  • Mutation
  • Peptides / metabolism
  • Proteasome Endopeptidase Complex
  • Receptors, Mating Factor
  • Receptors, Peptide / chemistry
  • Receptors, Peptide / metabolism*
  • Saccharomyces cerevisiae / cytology*
  • Signal Transduction / physiology*
  • Transcription Factors*
  • Ubiquitins / metabolism*
  • Vacuoles / enzymology

Substances

  • Ligands
  • Multienzyme Complexes
  • Peptides
  • Receptors, Mating Factor
  • Receptors, Peptide
  • Transcription Factors
  • Ubiquitins
  • Mating Factor
  • Hydrolases
  • Carboxypeptidases
  • Cathepsin A
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • Ligases
  • Lysine