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Hrs recognizes a hydrophobic amino acid cluster in cytokine receptors during ubiquitin-independent endosomal sorting.


ABSTRACT: Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is a component of the ESCRT-0 protein complex that captures ubiquitylated cargo proteins and sorts them to the lysosomal pathway. Although Hrs acts as a key transporter for ubiquitin-dependent endosomal sorting, we previously reported that Hrs is also involved in ubiquitin-independent endosomal sorting of interleukin-2 receptor ? (IL-2R?). Here, we show direct interactions between bacterially expressed Hrs and interleukin-4 receptor ? (IL-4R?), indicating that their binding is not required for ubiquitylation of the receptors, similar to the case for IL-2R?. Examinations of the Hrs binding regions of the receptors reveal that a hydrophobic amino acid cluster in both IL-2R? and IL-4R? is essential for the binding. Whereas the wild-type receptors are delivered to LAMP1-positive late endosomes, mutant receptors lacking the hydrophobic amino acid cluster are sorted to lysobisphosphatidic acid-positive late endosomes rather than LAMP1-positive late endosomes. We also show that the degradation of these mutant receptors is attenuated. Accordingly, Hrs functions during ubiquitin-independent endosomal sorting of the receptors by recognizing the hydrophobic amino acid cluster. These findings suggest the existence of a group of cargo proteins that have this hydrophobic amino acid cluster as a ubiquitin-independent sorting signal.

SUBMITTER: Amano Y 

PROVIDER: S-EPMC3083181 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Hrs recognizes a hydrophobic amino acid cluster in cytokine receptors during ubiquitin-independent endosomal sorting.

Amano Yuji Y   Yamashita Yuki Y   Kojima Katsuhiko K   Yoshino Kazuhisa K   Tanaka Nobuyuki N   Sugamura Kazuo K   Takeshita Toshikazu T  

The Journal of biological chemistry 20110301 17


Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is a component of the ESCRT-0 protein complex that captures ubiquitylated cargo proteins and sorts them to the lysosomal pathway. Although Hrs acts as a key transporter for ubiquitin-dependent endosomal sorting, we previously reported that Hrs is also involved in ubiquitin-independent endosomal sorting of interleukin-2 receptor β (IL-2Rβ). Here, we show direct interactions between bacterially expressed Hrs and interleukin-4 recep  ...[more]

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