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

Kanazawa, Chikako, Morita, Eiji, Yamada, Mitsuhiro, Ishii, Naoto, Miura, Shigeta, Asao, Hironobu, Yoshimori, Tamostu, Sugamura, Kazuo·2003·Biochemical and Biophysical Research Communications
DOI 10.1016/j.bbrc.2003.08.078
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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.

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  • Hrs and STAM deficiencies impair EGFR trafficking and degradation and lead to endocytic swelling.

    “Similarly, deficiencies in Hrs and STAM proteins impair EGFR trafficking and degradation and lead to gross endocytic swelling, characteristic of defects in cargo progression (11).”

    From Regulation of Epidermal Growth Factor Receptor Ubiquitination and Trafficking by the USP8·STAM Complex (2010) · cites this paper as [11]

  • The ESCRT-0 complex partitions cargo arriving at the sorting endosome between recycling and progression to the MVB.

    “The ESCRT-0 complex, consisting of adaptor proteins hepatocyte growth factor-regulated substrate (Hrs) and signal transducing adaptor molecule (STAM) (9), partitions cargo arriving at the sorting endosome between recycling and progression to the MVB (10 -13)”

    From Regulation of Epidermal Growth Factor Receptor Ubiquitination and Trafficking by the USP8·STAM Complex (2010) · cites this paper as [11]

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Metadata

Authors
Kanazawa, C., Morita, E., Yamada, M., Ishii, N., Miura, S., Asao, H., Yoshimori, T., & Sugamura, K.
Venue
Biochemical and Biophysical Research Communications
Publisher
Elsevier BV
Published
2003-10
Volume
309
Issue
4
Pages
848-856
ISSN
0006-291X
DOI
10.1016/j.bbrc.2003.08.078
Cited by
68
References
1
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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