The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Variability and Robustness in T Cell Activation from Regulated Heterogeneity in Protein Levels
Open accessAbstract
In T cells, the stochasticity of protein expression could contribute to the useful diversification of biological functions within a clonal population or interfere with accurate antigen discrimination. Combining computer modeling and single-cell measurements, we examined how endogenous variation in the expression levels of signaling proteins might affect antigen responsiveness during T cell activation. We found that the CD8 co-receptor fine-tunes activation thresholds, whereas the soluble hematopoietic phosphatase 1 (SHP-1) digitally regulates cell responsiveness. Stochastic variation in the expression of these proteins generates substantial diversity of activation within a clonal population of T cells, but co-regulation of CD8 and SHP-1 levels ultimately limits this very diversity. These findings reveal how eukaryotic cells can draw on regulated variation in gene expression to achieve phenotypic variability in a controlled manner.
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Cites
Stochastic Gene Expression in a Single Cell
Elowitz, M. B., Levine, A. J., Siggia, E. D., & Swain, P. S. (2002) · Science · doi:10.1126/science.1070919 · Cited by 5,441
Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise
Newman, J. R. S., Ghaemmaghami, S., Ihmels, J., Breslow, D. K., Noble, M., DeRisi, J. L., & Weissman, J. S. (2006) · Nature · doi:10.1038/nature04785 · Cited by 1,483
Noise in protein expression scales with natural protein abundance
Bar-Even, A., Paulsson, J., Maheshri, N., Carmi, M., O'Shea, E., Pilpel, Y., & Barkai, N. (2006) · Nature Genetics · doi:10.1038/ng1807 · Cited by 807
TCR ligand discrimination is enforced by competing ERK positive and SHP-1 negative feedback pathways
Štefanová, I., Hemmer, B., Vergelli, M., Martin, R., Biddison, W. E., & Germain, R. N. (2003) · Nature Immunology · doi:10.1038/ni895 · Cited by 465
Self-citation
Cited by
PD-1 signaling in primary T cells
Riley, J. L. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00767.x · Cited by 778
“SHP-1 was recently shown to be a digital regulator of T-cell activation (79).”
BackgroundTowards a rigorous assessment of systems biology models: the DREAM3 challenges
Prill, R. J., Marbach, D., Saez-Rodriguez, J., Sorger, P. K., Alexopoulos, L. G., Xue, X., Clarke, N. D., Altan-Bonnet, G., & Stolovitzky, G. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009202 · Cited by 439
Self-citationDecanalization and the origin of complex disease
Gibson, G. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2502 · Cited by 285
Ebert, P. J. R., Jiang, S., Xie, J., Li, Q.-J., & Davis, M. M. (2009) · Nature Immunology · doi:10.1038/ni.1797 · Cited by 251
Surviving apoptosis: life–death signaling in single cells
Flusberg, D. A., & Sorger, P. K. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.03.003 · Cited by 149
Metadata
- Authors
- Feinerman, O., Veiga, J., Dorfman, J. R., Germain, R. N., & Altan-Bonnet, G.
- Venue
- Science
- Published
- 2008-08-22
- Volume
- 321
- Issue
- 5892
- Pages
- 1081-1084
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2063131697
- Cited by
- 338
- References
- 4
- FWCI
- 9.43
- Type
- journal article
- Language
- en
- Open access
- green
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