PMID: 19690332 RLIMS-P 3 Check other iTextMine results Issue Report
Title
| 1. | Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. |
Abstract
| 2. | Protein phosphorylation events during T cell receptor (TCR) signaling control the formation of complexes among proteins proximal to the TCR, the activation of kinase cascades, and the activation of transcription factors; however, the mode and extent of the influence of phosphorylation in coordinating the diverse phenomena associated with T cell activation are unclear. |
| 3. | Therefore, we used the human Jurkat T cell leukemia cell line as a model system and performed large-scale quantitative phosphoproteomic analyses of TCR signaling. |
| 4. | We identified 10,665 unique phosphorylation sites, of which 696 showed TCR-responsive changes. |
| 5. | In addition, we analyzed broad trends in phosphorylation data sets to uncover underlying mechanisms associated with T cell activation. |
| 6. | We found that, upon stimulation of the TCR, phosphorylation events extensively targeted protein modules involved in all of the salient phenomena associated with T cell activation: patterning of surface proteins, endocytosis of the TCR, formation of the F-actin cup, inside-out activation of integrins, polarization of microtubules, production of cytokines, and alternative splicing of messenger RNA. |
| 7. | Further, case-by-case analysis of TCR-responsive phosphorylation sites on proteins belonging to relevant functional modules together with network analysis allowed us to deduce that serine-threonine (S-T) phosphorylation modulated protein-protein interactions (PPIs) in a system-wide fashion. |
| 8. | We also provide experimental support for this inference by showing that phosphorylation of tubulin on six distinct serine residues abrogated PPIs during the assembly of microtubules. |
| 9. | We propose that modulation of PPIs by stimulus-dependent changes in S-T phosphorylation state is a widespread phenomenon applicable to many other signaling systems. |
Loading...
Loading data
Legend: SUBSTRATE KINASE INTERACTANT SITE GENE MIRNA ANOMALY EXPRESSION DISEASE OUTCOME/RESPONSE SR_DRUG DRUG CELL TRIGGER Normalized
Tool: RLIMS-P
| PTM enzyme | Substrate | Site | Sentence |
|---|---|---|---|
| tubulin | Ser | 8 | |
| S-T | 9 | ||
| serine-threonine (S-T) | protein-protein interactions (PPIs) | Ser, Thr | 7 |