Abstract
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 p56lck, actin polymerization, and dynamin. Constitutive signaling and degradation represents a feature of the pre-TCR because the γδTCR 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 γδTCR-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.
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Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 12:48 p.m.) |
Deposited | 2 years, 1 month ago (July 25, 2023, 7:28 a.m.) |
Indexed | 2 months, 2 weeks ago (June 12, 2025, 11:53 a.m.) |
Issued | 23 years, 2 months ago (June 10, 2002) |
Published | 23 years, 2 months ago (June 10, 2002) |
Published Online | 23 years, 2 months ago (June 10, 2002) |
Published Print | 23 years, 2 months ago (June 17, 2002) |
@article{Panigada_2002, title={Constitutive Endocytosis and Degradation of the Pre-T Cell Receptor}, volume={195}, ISSN={0022-1007}, url={http://dx.doi.org/10.1084/jem.20020047}, DOI={10.1084/jem.20020047}, number={12}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Panigada, Maddalena and Porcellini, Simona and Barbier, Eliane and Hoeflinger, Sonja and Cazenave, Pierre-André and Gu, Hua and Band, Hamid and von Boehmer, Harald and Grassi, Fabio}, year={2002}, month=jun, pages={1585–1597} }