dorsal/arxiv
View SchemaCombinatorial complexity and dynamical restriction of network flows in signal transduction
| Authors | James R. Faeder, Michael L. Blinov, Byron Goldstein, William S. Hlavacek |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0411021 |
| URL | https://arxiv.org/abs/q-bio/0411021 |
Abstract
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 Fc$\epsilon$RI, 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.
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"abstract": "The activities and interactions of proteins that govern the cellular response\nto a signal generate a multitude of protein phosphorylation states and\nheterogeneous protein complexes. Here, using a computational model that\naccounts for 307 molecular species implied by specified interactions of four\nproteins involved in signalling by the immunoreceptor Fc$\\epsilon$RI, we\ndetermine the relative importance of molecular species that can be generated\nduring signalling, chemical transitions among these species, and reaction paths\nthat lead to activation of the protein tyrosine kinase (PTK) Syk. By all of\nthese measures and over 2- and 10-fold ranges of model parameters--rate\nconstants and initial concentrations--only a small portion of the biochemical\nnetwork is active. The spectrum of active complexes, however, can be shifted\ndramatically, even by a change in the concentration of a single protein, which\nsuggests that the network can produce qualitatively different responses under\ndifferent cellular conditions and in response to different inputs. Reduced\nmodels that reproduce predictions of the full model for a particular set of\nparameters lose their predictive capacity when parameters are varied over\n2-fold ranges.",
"arxiv_id": "q-bio/0411021",
"authors": [
"James R. Faeder",
"Michael L. Blinov",
"Byron Goldstein",
"William S. Hlavacek"
],
"categories": [
"q-bio.MN",
"q-bio.SC"
],
"title": "Combinatorial complexity and dynamical restriction of network flows in signal transduction",
"url": "https://arxiv.org/abs/q-bio/0411021"
},
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