2004/11/05 by James R. Faeder, Michael L. Blinov, Faeder, James R. +5
Biochemistry, Genetics and Molecular Biology · #FOS: Biological sciences #Molecular Networks (q-bio.MN) #Subcellular Processes (q-bio.SC) #q-bio.MN #q-bio.SC
paper · pdf · doi:10.48550/arxiv.q-bio/0411021
36 pages, 4 figures, 3 tables, 2 appendices. Submitted to Systems Biology
arxiv created 2004/11/05 · arxiv updated 2009/12/01
The activities and interactions of proteins that govern the cellular response to a signal generate a multitude of protein phosphorylation states and heterogeneous protein complexes. Here, using a computational model that accounts for 307 molecular species implied by specified interactions of four proteins involved in signalling by the immunoreceptor FcεRI, we determine the relative importance of molecular species that can be generated during signalling, chemical transitions among these species, and reaction paths that lead to activation of the protein tyrosine kinase (PTK) Syk. By all of these measures and over 2- and 10-fold ranges of model parameters--rate constants and initial concentrations--only a small portion of the biochemical network is active. The spectrum of active complexes, however, can be shifted dramatically, even by a change in the concentration of a single protein, which suggests that the network can produce qualitatively different responses under different cellular conditions and in response to different inputs. Reduced models that reproduce predictions of the full model for a particular set of parameters lose their predictive capacity when parameters are varied over 2-fold ranges.