Effects of deficiencies of STAMs and Hrs, mammalian class E Vps proteins, on receptor downregulation

Chikako Kanazawa, Eiji Morita, Mitsuhiro Yamada, Naoto Ishii, Shigeta Miura, Hironobu Asao, Tamostu Yoshimori, Kazuo Sugamura

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

The STAM family proteins, STAM1 and STAM2/EAST/Hbp, are phosphotyrosine proteins that contain SH3 domains and ubiquitin-interacting motifs. Their yeast homologue, Hse1, and its binding protein, Vps27, are involved in the vacuolar membrane transport machinery. Here we show that STAM1 and STAM2 are localized to the endosomal membrane. Some of these complexes contain Eps15, an endocytic protein, which accumulates in clumps upon expression of a dominant-negative form of Vps4-A, an AAA-type ATPase, that is required for normal endosome function. These results support the idea that the STAMs are mammalian vacuolar protein sorting (Vps) proteins. We also demonstrate that ligand-mediated epidermal growth factor receptor (EGFR) degradation is partially but not completely impaired in both Hrs-/- and STAM1-/-STAM2 -/- mouse embryonic fibroblasts. Furthermore, endosome swelling is seen in both Hrs-/- and STAM1-/-STAM2-/- cells. These results suggest that the STAMs and Hrs play important roles in the mammalian endosomal/vacuolar protein sorting pathway.

Original languageEnglish
Pages (from-to)848-856
Number of pages9
JournalBiochemical and biophysical research communications
Volume309
Issue number4
DOIs
Publication statusPublished - 2003 Oct 3

Keywords

  • Hrs
  • MVB sorting
  • STAM1
  • STAM2
  • Vps

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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