Early endosomal localization of hrs requires a sequence within the proline- and glutamine-rich region but not the FYVE finger.
Hrs is an early endosomal protein that is tyrosine-phosphorylated in cells stimulated with growth factors. Hrs is thought to play a regulatory role in endocytosis of growth factor-receptor complexes through early endosomes. Early endosomal localization of Hrs seems to be essential for Hrs to exert its function in the endocytosis. Hrs has a FYVE finger domain that binds specifically to phosphatidylinositol 3-phosphate in vitro. The FYVE finger is a likely domain that mediates membrane association of endosomal proteins. In this study, we examined whether the FYVE finger participates in early endosomal targeting of Hrs. Hrs with a zinc binding-defective FYVE finger was still localized to early endosomes. In addition, the N-terminal FYVE finger-containing fragment of Hrs showed a cytosolic distribution in mammalian cells. These results indicate that the FYVE finger is not required for the localization of Hrs to early endosomes. Furthermore, by analyzing a series of deletion mutants of Hrs, we identified a sequence of about 100 amino acids within the C-terminal proline- and glutamine-rich region as a domain essential for the targeting of Hrs to early endosomes.
Hayakawa
A
A
Department of Life Science, Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
Kitamura
N
N
D000818:Animals; D001665:Binding Sites; D001692:Biological Transport / Q000235:genetics; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000378:metabolism*; D005973:Glutamine / Q000235:genetics; D006367:HeLa Cells; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011392:Proline / Q000235:genetics; D016335:Zinc Fingers
D056827:Endosomal Sorting Complexes Required for Transport; D010750:Phosphoproteins; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate; D005973:Glutamine; D017228:Hepatocyte Growth Factor; D011392:Proline