Capturing cell-fate decisions from the molecular signatures of a receptor-dependent signaling response.

ABSTRACT: We examined responses of the B-cell antigen receptor-dependent intracellular signaling network to targeted perturbations induced through siRNA-mediated depletion of select signaling intermediates. The constituent nodes displayed graded sensitivities, which resulted from the differential effects of perturbations on the kinetic and quantitative aspects of phosphorylation at each node. By taking the rate of initial phosphorylation, rate of subsequent dephosphorylation, and the total intensity of phosphorylation at each node as separate signaling parameters, we generated data-driven models that accurately predicted the cellular responses of apoptosis, proliferation, and cytokine secretion. Importantly, the effects of perturbation on the primary target alone did not yield successful models. Rat

SUBMITTER: Kumar D 

PROVIDER: S-EPMC2174630 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature