Reference - Detail
| RRC ID | 28633 |
|---|---|
| Author | Yamashita Y, Kojima K, Tsukahara T, Agawa H, Yamada K, Amano Y, Kurotori N, Tanaka N, Sugamura K, Takeshita T. |
| Title | Ubiquitin-independent binding of Hrs mediates endosomal sorting of the interleukin-2 receptor beta-chain. |
| Journal | J Cell Sci |
| Abstract |
Several lines of evidence have revealed that ubiquitylation of membrane proteins serves as a signal for endosomal sorting into lysosomes or lytic vacuoles. The hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) interacts with ubiquitylated cargoes through its ubiquitin-interacting-motif domain (UIM domain), and plays an essential early role in endosomal sorting. Here, we show that the C-terminal region of Hrs, which does not contain the UIM domain, can bind to interleukin-2 receptor beta (IL-2Rbeta). We found a direct interaction between bacterially expressed IL-2Rbeta and Hrs in GST pull-down assays, indicating that their binding is independent of ubiquitin. Trafficking and degradation assays revealed that, similarly to wild-type IL-2Rbeta, an IL-2Rbeta mutant lacking all the cytoplasmic lysine residues is sorted from Hrs-positive early endosomes to LAMP1-positive late endosomes, resulting in degradation of the receptor. By contrast, an IL-2Rbeta mutant lacking the Hrs-binding region passes through early endosomes and is mis-sorted to compartments positive for the transferrin receptor. The latter mutant exhibits attenuated degradation. Taken together, these results indicate that precise sorting of IL-2Rbeta from early to late endosomes is mediated by Hrs, a known sorting component of the ubiquitin-dependent machinery, in a manner that is independent of UIM-ubiquitin binding. |
| Volume | 121(Pt 10) |
| Pages | 1727-38 |
| Published | 2008-5-15 |
| DOI | 10.1242/jcs.024455 |
| PII | jcs.024455 |
| PMID | 18445679 |
| MeSH | Cell Line Endosomal Sorting Complexes Required for Transport Endosomes / metabolism* Endosomes / ultrastructure Humans Interleukin-2 Receptor beta Subunit / chemistry Interleukin-2 Receptor beta Subunit / genetics Interleukin-2 Receptor beta Subunit / metabolism* Lysosome-Associated Membrane Glycoproteins / metabolism* Phosphoproteins / chemistry Phosphoproteins / metabolism* Protein Structure, Tertiary Protein Transport Recombinant Fusion Proteins / metabolism Ubiquitin / metabolism* |
| IF | 4.573 |
| Times Cited | 15 |
| WOS Category | CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Wikipedia |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| DNA material | pSR-Flag-wt (RDB08501) pSR-Flag-d268 (RDB08502) pSR-Flag-d348 (RDB08503) pSR-Flag-d357 (RDB08504) pSR-Flag-d380 (RDB08505) pSR-Flag-d394 (RDB08506) pSR-Flag-d412 (RDB08507) pSR-Flag-d268-410 (RDB08508) pSR-Flag-d268-348 (RDB08509) pSR-Flag-d349-410 (RDB08510) |