title: The ubiquitin-proteasome pathway regulates lysosomal degradation of the growth hormone receptor and its ligand.
abstract: The growth hormone (GH) receptor (GHR) is a mammalian plasma membrane protein whose internalization is mediated by the ubiquitin-proteasome pathway. GH internalization and degradation are inhibited when cells are treated with proteasome inhibitors. Here we show that a GHR truncated at residue 369 can enter the cells in the presence of a proteasome inhibitor, but that the subsequent lysosomal degradation of GH is blocked. Lysosomal inhibitors prolong the half-life of both receptor and ligand. Experiments with antibodies against different receptor tail sections show that degradation of the GHR cytosolic domain precedes degradation of the extracellular GH-binding domain. A possible role for the ubiquitin-proteasome pathway in the degradation of the receptor and ligand is discussed.
authors.affiliation: Department of Cell Biology, University Medical Center Utrecht and Institute of Biomembranes, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: van Kerkhof
authors.forename: G J
authors.initials: GJ
authors.lastname: Strous
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004705:Endocytosis; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008247:Lysosomes / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D046988:Proteasome Endopeptidase Complex; D011817:Rabbits; D011986:Receptors, Somatotropin / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D008024:Ligands; D009097:Multienzyme Complexes; D011986:Receptors, Somatotropin; D025801:Ubiquitin; D019382:Human Growth Hormone; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex