| pubmed-article:12070286 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12070286 | lifeskim:mentions | umls-concept:C0007634 | lld:lifeskim |
| pubmed-article:12070286 | lifeskim:mentions | umls-concept:C0597357 | lld:lifeskim |
| pubmed-article:12070286 | lifeskim:mentions | umls-concept:C0014139 | lld:lifeskim |
| pubmed-article:12070286 | lifeskim:mentions | umls-concept:C0699900 | lld:lifeskim |
| pubmed-article:12070286 | lifeskim:mentions | umls-concept:C0243125 | lld:lifeskim |
| pubmed-article:12070286 | pubmed:issue | 12 | lld:pubmed |
| pubmed-article:12070286 | pubmed:dateCreated | 2002-6-18 | lld:pubmed |
| pubmed-article:12070286 | pubmed:abstractText | The pre-T cell receptor (TCR) signals constitutively in the absence of putative ligands on thymic stroma and signal transduction correlates with translocation of the pre-TCR into glycolipid-enriched microdomains (rafts) in the plasma membrane. Here, we show that the pre-TCR is constitutively routed to lysosomes after reaching the cell surface. The cell-autonomous down-regulation of the pre-TCR requires activation of the src-like kinase p56(lck), actin polymerization, and dynamin. Constitutive signaling and degradation represents a feature of the pre-TCR because the gammadeltaTCR expressed in the same cell line does not exhibit these features. This is also evident by the observation that the protein adaptor/ubiquitin ligase c-Cbl is phosphorylated and selectively translocated into rafts in pre-TCR- but not gammadeltaTCR-expressing cells. A role of c-Cbl-mediated ubiquitination in pre-TCR degradation is supported by the reduction of degradation through pharmacological inhibition of the proteasome and through a dominant-negative c-Cbl ubiquitin ligase as well as by increased pre-TCR surface expression on immature thymocytes in c-Cbl-deficient mice. The pre-TCR internalization contributes significantly to the low surface level of the receptor on developing T cells, and may in fact be a requirement for optimal pre-TCR function. | lld:pubmed |
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| pubmed-article:12070286 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12070286 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12070286 | pubmed:citationSubset | IM | lld:pubmed |
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