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 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.
Constitutive endocytosis and degradation of the pre-T cell receptor / M. Panigada, S. Porcellini, E. Barbier, S. Hoeflinger, P.A. Cazenave, H. Gu, H. Band, H. von Boehmer, F. Grassi. - In: JOURNAL OF EXPERIMENTAL MEDICINE. - ISSN 0022-1007. - 195:12(2002), pp. 1585-1597.
|Titolo:||Constitutive endocytosis and degradation of the pre-T cell receptor|
GRASSI, FABIO MARIA (Ultimo)
|Parole Chiave:||c-Cbl; Pre-TCR; T cell development; Thymocyte; Ubiquitin|
|Settore Scientifico Disciplinare:||Settore BIO/13 - Biologia Applicata|
|Data di pubblicazione:||2002|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1084/jem.20020047|
|Appare nelle tipologie:||01 - Articolo su periodico|