Src-like adaptor protein regulates TCR expression on thymocytes by linking the ubiquitin ligase c-Cbl to the TCR complex
Copyright policy )Src-like adaptor protein regulates TCR expression on thymocytes by linking the ubiquitin ligase c-Cbl to the TCR complex
The adaptor molecule SLAP and E3 ubiquitin ligase c-Cbl each regulate expression of T cell receptor (TCR)-CD3 on thymocytes. Here we provide genetic and biochemical evidence that both molecules function in the same pathway. TCR-CD3 expression was similar in the absence of SLAP and/or c-Cbl. SLAP and c-Cbl were found to interact, and their expression together downregulated CD3epsilon. This required multiple domains in SLAP and the ring finger of c-Cbl. Furthermore, expression of SLAP and c-Cbl together induced TCRzeta ubiquitination and degradation, preventing the accumulation of fully assembled recycling TCR complexes. These studies indicate that SLAP links the E3 ligase activity of c-Cbl to the TCR, allowing for stage-specific regulation of TCR expression.
- Northwestern University United States
- Columbia University United States
- King’s University United States
- Howard Hughes Medical Institute United States
- University of California, San Francisco United States
CD3 Complex, T-Lymphocytes, Immunoblotting, Proto-Oncogene Proteins pp60(c-src), Receptors, Antigen, T-Cell, Flow Cytometry, Transfection, Mice, Mutant Strains, Jurkat Cells, Mice, Animals, Humans, Proto-Oncogene Proteins c-cbl
CD3 Complex, T-Lymphocytes, Immunoblotting, Proto-Oncogene Proteins pp60(c-src), Receptors, Antigen, T-Cell, Flow Cytometry, Transfection, Mice, Mutant Strains, Jurkat Cells, Mice, Animals, Humans, Proto-Oncogene Proteins c-cbl
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).86 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!