STAM and Hrs Are Subunits of a Multivalent Ubiquitin-binding Complex on Early Endosomes

Bache, Kristi G.; Raiborg, Camilla; Mehlum, Anja; Stenmark, Harald

doi:10.1074/jbc.m210843200

Cited by 286

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STAM and Hrs Are Subunits of a Multivalent Ubiquitin-binding Complex on Early Endosomes

Bache, Kristi G., Raiborg, Camilla, Mehlum, Anja, Stenmark, Harald·2003·Journal of Biological Chemistry

DOI 10.1074/jbc.m210843200

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Abstract

STAM1 and STAM2, which have been identified as regulators of receptor signaling and trafficking, interact directly with Hrs, which mediates the endocytic sorting of ubiquitinated membrane proteins. The STAM proteins interact with the same coiled-coil domain that is involved in the targeting of Hrs to endosomes. In this work, we show that STAM1 and STAM2, as well as an endocytic regulator protein, Eps15, can be co-immunoprecipitated with Hrs both from membrane and cytosolic fractions and that recombinant Hrs, STAM1/STAM2, and Eps15 form a ternary complex. We find that overexpression of Hrs causes a strong recruitment of STAM2 to endosome membranes. Moreover, STAM2, like Hrs and Eps15, binds ubiquitin, and Hrs, STAM2, and Eps15 colocalize with ubiquitinated proteins in clathrin-containing endosomal microdomains. The localization of Hrs, STAM2, Eps15, and clathrin to endosome membranes is controlled by the AAA ATPase mVps4, which has been implicated in multivesicular body formation. Depletion of cellular Hrs by small interfering RNA results in a strongly reduced recruitment of STAM2 to endosome membranes and an impaired degradation of endocytosed epidermal growth factor receptors. We propose that Hrs, Eps15, and STAM proteins function in a multivalent complex that sorts ubiquitinated proteins into the multivesicular body pathway.

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STAM2 together with Hrs plays a regulatory role in endocytic trafficking of growth factor receptor complexes through early endosomes.
“STAM2 (Hbp), together with Hrs, plays a regulatory role in endocytic trafficking of growth factor receptor complexes through early endosomes (4).”
From Essential Role of Ubiquitin-Specific Protease 8 for Receptor Tyrosine Kinase Stability and Endocytic Trafficking In Vivo (2007) · cites this paper as [4]

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TSG101/Mammalian VPS23 and Mammalian VPS28 Interact Directly and Are Recruited to VPS4-induced Endosomes
Bishop, N., & Woodman, P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009863200 · Cited by 187

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Authors: Bache, K. G., Raiborg, C., Mehlum, A., & Stenmark, H.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2003-04
Volume: 278
Issue: 14
Pages: 12513-12521
ISSN: 0021-9258
DOI: 10.1074/jbc.m210843200
Cited by: 286
References: 2
Language: en
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 6409 d)

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STAM and Hrs Are Subunits of a Multivalent Ubiquitin-binding Complex on Early Endosomes

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