T-cell receptor (TCR) signaling is essential for the function of T cells and negatively regulated by the E3 ubiquitin-protein ligases CBL and CBLB Here, we combined mouse genetics and affinity purification coupled to quantitative mass spectrometry to monitor the dynamics of the CBL and CBLB signaling complexes that assemble in normal T cells over 600 seconds of TCR stimulation. We identify most previously known CBL and CBLB interacting partners, as well as a majority of proteins that have not yet been implicated in those signaling complexes. We exploit correlations in protein association with CBL and CBLB as a function of time of TCR stimulation for predicting the occurrence of direct physical association between them. By combining co-recruitment analysis with biochemical analysis, we demonstrated that the CD5 transmembrane receptor constitutes a key scaffold for CBL- and CBLB-mediated ubiquitylation following TCR engagement. Our results offer an integrated view of the CBL and CBLB signaling complexes induced by TCR stimulation and provide a molecular basis for their negative regulatory function in normal T cells.
Pubmed ID: 27474268 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Centralized, standards compliant, public data repository for proteomics data, including protein and peptide identifications, post-translational modifications and supporting spectral evidence. Originally it was developed to provide a common data exchange format and repository to support proteomics literature publications. This remit has grown with PRIDE, with the hope that PRIDE will provide a reference set of tissue-based identifications for use by the community. The future development of PRIDE has become closely linked to HUPO PSI. PRIDE encourages and welcomes direct user submissions of protein and peptide identification data to be published in peer-reviewed publications. Users may Browse public datasets, use PRIDE BioMart for custom queries, or download the data directly from the FTP site. PRIDE has been developed through a collaboration of the EMBL-EBI, Ghent University in Belgium, and the University of Manchester.
View all literature mentionsCurated protein-protein and genetic interaction repository of raw protein and genetic interactions from major model organism species, with data compiled through comprehensive curation efforts.
View all literature mentionsA data repository for proteomic data sets. The ProteomeExchange consortium, as a whole, aims to provide a coordinated submission of MS proteomics data to the main existing proteomics repositories, as well as to encourage optimal data dissemination. ProteomeXchange provides access to a number of public databases, and users can access and submit data sets to the consortium's PRIDE database and PASSEL/PeptideAtlas.
View all literature mentionsRandomized controlled trial being conducted at two clinical centers in the United States to learn more about the effects of weight loss on urinary incontinence. About 330 overweight women aged 30 or older will participate and will be followed for 18 months. Efficacy of weight reduction as a treatment for urinary incontinence will be examined at 6 months following the intensive weight control program, and the sustained impact of the intervention will be examined at 18 months. To increase the maintenance of weight reduction and facilitate evaluation of the enduring impact of weight loss on urinary incontinence, they propose to study a motivation-based weight maintenance program. At the end of the intensive weight control program, women randomized to the weight loss program will be randomized to either a 12-month skill-based maintenance intervention or to a motivation-based maintenance intervention. The maintenance interventions maximize the potential for sustained weight loss and will allow them to determine if long-term weight reduction will produce continued improvement in urinary incontinence.
View all literature mentionsA quantitative proteomics software package for analyzing large-scale mass-spectrometric data sets. It is a set of algorithms that include peak detection and scoring of peptides, mass calibration, database searches for protein identification, protein quantification, and provides summary statistics.
View all literature mentionsA software which acquires and processes data sets, primarily through the Xcalibur system.
View all literature mentionslaboratory mouse with name B6.129P2-Cd5tm1Cgn from MGI.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionslaboratory mouse with name C57BL/6N from MGI.
View all literature mentions