The Hrs/STAM complex in the downregulation of receptor tyrosine kinases.
Cell surface receptor proteins that have undergone endocytosis are transported to the endosome. From the endosome, ligand-activated receptor tyrosine kinases are further transported to the lysosome for degradation, a process called "receptor downregulation." By contrast, nutrient receptors, such as those for low-density lipoprotein and transferrin, are recycled back to the plasma membrane. Sorting of these two types of receptors occurs at the endosome, where ubiquitination of receptor proteins serves as the sorting signal. Namely, ubiquitinated receptors are incorporated into the lysosomal degradation pathway, whereas those that are not ubiquitinated are returned to the cell surface. Hrs and STAM are proteins that form a complex on the endosomal membrane. Recent studies have shown that the Hrs/STAM complex binds ubiquitin moieties and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes.
Komada
Masayuki
M
Department of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-16 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan. makomada@bio.titech.ac.jp
Kitamura
Naomi
N
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D056827:Endosomal Sorting Complexes Required for Transport; D006801:Humans; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D056827:Endosomal Sorting Complexes Required for Transport; D046912:Multiprotein Complexes; D010750:Phosphoproteins; C109775:STAM protein, human; C491648:Stam protein, mouse; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate; D020794:Receptor Protein-Tyrosine Kinases