Variability and robustness in T cell activation from regulated heterogeneity in protein levels. Export

@article{citeulike:3188437, abstract = {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.}, address = {ImmunoDynamics Group, Program in Computational Biology and Immunology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 460, New York, NY 10065, USA.}, author = {Feinerman, O. and Veiga, J. and Dorfman, J. R. and Germain, R. N. and Altan-Bonnet, G.}, citeulike-article-id = {3188437}, citeulike-linkout-0 = {http://dx.doi.org/10.1126/science.1158013}, citeulike-linkout-1 = {http://www.sciencemag.org/cgi/content/abstract/321/5892/1081}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18719282}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18719282}, day = {22}, doi = {10.1126/science.1158013}, issn = {1095-9203}, journal = {Science (New York, N.Y.)}, keywords = {altan-bonnet, mskcc}, month = {August}, number = {5892}, pages = {1081--1084}, posted-at = {2008-09-03 23:36:51}, priority = {2}, title = {Variability and robustness in T cell activation from regulated heterogeneity in protein levels.}, url = {http://dx.doi.org/10.1126/science.1158013}, volume = {321}, year = {2008} }

TY - JOUR ID - citeulike:3188437 L3 - citeulike-article-id:3188437 N2 - 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. IS - 5892 JF - Science (New York, N.Y.) SN - 1095-9203 AD - ImmunoDynamics Group, Program in Computational Biology and Immunology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 460, New York, NY 10065, USA. EP - 1084 TI - Variability and robustness in T cell activation from regulated heterogeneity in protein levels. VL - 321 SP - 1081 KW - altan-bonnet KW - mskcc AU - Feinerman, O AU - Veiga, J AU - Dorfman, JR AU - Germain, RN AU - Altan-Bonnet, G PY - 2008/08/22/ UR - http://dx.doi.org/10.1126/science.1158013 ER -