Crossref journal-article
Rockefeller University Press
The Journal of Experimental Medicine (291)
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.

Bibliography

Panigada, M., Porcellini, S., Barbier, E., Hoeflinger, S., Cazenave, P.-A., Gu, H., Band, H., von Boehmer, H., & Grassi, F. (2002). Constitutive Endocytosis and Degradation of the Pre-T Cell Receptor. The Journal of Experimental Medicine, 195(12), 1585–1597.

Authors 9
  1. Maddalena Panigada (first)
  2. Simona Porcellini (additional)
  3. Eliane Barbier (additional)
  4. Sonja Hoeflinger (additional)
  5. Pierre-André Cazenave (additional)
  6. Hua Gu (additional)
  7. Hamid Band (additional)
  8. Harald von Boehmer (additional)
  9. Fabio Grassi (additional)
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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)
Funders 0

None

@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} }