A Systems Model of Signaling Identifies a Molecular Basis Set for Cytokine-Induced Apoptosis Export

@article{citeulike:432065, abstract = {Signal transduction pathways control cellular responses to stimuli, but it is unclear how molecular information is processed as a network. We constructed a systems model of 7980 intracellular signaling events that directly links measurements to 1440 response outputs associated with apoptosis. The model accurately predicted multiple time-dependent apoptotic responses induced by a combination of the death-inducing cytokine tumor necrosis factor with the prosurvival factors epidermal growth factor and insulin. By capturing the role of unsuspected autocrine circuits activated by transforming growth factor-{alpha} and interleukin-1{alpha}, the model revealed new molecular mechanisms connecting signaling to apoptosis. The model derived two groupings of intracellular signals that constitute fundamental dimensions (molecular "basis axes") within the apoptotic signaling network. Projection along these axes captures the entire measured apoptotic network, suggesting that cell survival is determined by signaling through this canonical basis set. 10.1126/science.1116598}, author = {Janes, Kevin A. and Albeck, John G. and Gaudet, Suzanne and Sorger, Peter K. and Lauffenburger, Douglas A. and Yaffe, Michael B.}, citeulike-article-id = {432065}, citeulike-linkout-0 = {http://dx.doi.org/10.1126/science.1116598}, citeulike-linkout-1 = {http://www.sciencemag.org/cgi/content/abstract/310/5754/1646}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/16339439}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=16339439}, day = {9}, doi = {10.1126/science.1116598}, journal = {Science}, keywords = {biology, systems}, month = {December}, number = {5754}, pages = {1646--1653}, posted-at = {2006-05-07 02:36:42}, priority = {2}, title = {A Systems Model of Signaling Identifies a Molecular Basis Set for Cytokine-Induced Apoptosis}, url = {http://dx.doi.org/10.1126/science.1116598}, volume = {310}, year = {2005} }

TY - JOUR ID - citeulike:432065 L3 - citeulike-article-id:432065 N2 - Signal transduction pathways control cellular responses to stimuli, but it is unclear how molecular information is processed as a network. We constructed a systems model of 7980 intracellular signaling events that directly links measurements to 1440 response outputs associated with apoptosis. The model accurately predicted multiple time-dependent apoptotic responses induced by a combination of the death-inducing cytokine tumor necrosis factor with the prosurvival factors epidermal growth factor and insulin. By capturing the role of unsuspected autocrine circuits activated by transforming growth factor-{alpha} and interleukin-1{alpha}, the model revealed new molecular mechanisms connecting signaling to apoptosis. The model derived two groupings of intracellular signals that constitute fundamental dimensions (molecular "basis axes") within the apoptotic signaling network. Projection along these axes captures the entire measured apoptotic network, suggesting that cell survival is determined by signaling through this canonical basis set. 10.1126/science.1116598 IS - 5754 JF - Science EP - 1653 TI - A Systems Model of Signaling Identifies a Molecular Basis Set for Cytokine-Induced Apoptosis VL - 310 SP - 1646 KW - biology KW - systems AU - Janes, Kevin AU - Albeck, John AU - Gaudet, Suzanne AU - Sorger, Peter AU - Lauffenburger, Douglas AU - Yaffe, Michael PY - 2005/12/09/ UR - http://dx.doi.org/10.1126/science.1116598 ER -