@article{oai:soar-ir.repo.nii.ac.jp:00003800,
 author = {Amano,  Yuji and Yamashita,  Yuki and Kojima,  Katsuhiko and Yoshino,  Kazuhisa and Tanaka,  Nobuyuki and Sugamura,  Kazuo and Takeshita,  Toshikazu},
 issue = {17},
 journal = {JOURNAL OF BIOLOGICAL CHEMISTRY},
 month = {Apr},
 note = {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 beta (IL-2R beta). Here, we show direct interactions between bacterially expressed Hrs and interleukin-4 receptor alpha (IL-4R alpha), indicating that their binding is not required for ubiquitylation of the receptors, similar to the case for IL-2R beta. Examinations of the Hrs binding regions of the receptors reveal that a hydrophobic amino acid cluster in both IL-2R beta and IL-4R alpha 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., Article, JOURNAL OF BIOLOGICAL CHEMISTRY. 286(17):15458-15472 (2011)},
 pages = {15458--15472},
 title = {Hrs Recognizes a Hydrophobic Amino Acid Cluster in Cytokine Receptors during Ubiquitin-independent Endosomal Sorting},
 volume = {286},
 year = {2011}
}