cGMP signaling: probing antagonistic cyclic nucleotide platelet signals by modeling and experiment

Dandekar, T.; Friebe, A.; Feil, R.; Dittrich, M.; Breitenbach, T.; Englert, N.; Osmanoglu, O.; rukoyatkina, n.; Wangorsch, G.; Butt, E.; Gambaryan, S.

doi:10.1101/2021.02.01.429103

bioRxiv · 10.1101/2021.02.01.429103

cGMP signaling: probing antagonistic cyclic nucleotide platelet signals by modeling and experiment

Dandekar, T.·Friebe, A.·Feil, R.·Dittrich, M.·Breitenbach, T.·Englert, N.·Osmanoglu, O.·rukoyatkina, n.·Wangorsch, G.·Butt, E.·Gambaryan, S.

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Abstract

BackgroundThe cyclic nucleotides cAMP and cGMP inhibit platelet activation. ResultsWe extended an older model and systematically integrated drugs as external stimuli. Data driven modeling allowed us to design models that provide a quantitative output for quantitative input information. This relies on condensed information about involved regulation and modeling of pharmacological interventions by systematic optimization methods. By multi-experiment fitting, we validated our model optimizing the parameters of the model. In addition, we show how the output of the developed cGMP model can be used as input for a modular model of VASP phosphorylation and for the activity of cAMP and cGMP pathways in platelets. ConclusionsWe present a model for cGMP signaling and VASP phosphorylation, that allows to estimate drug action on any of the inhibitory cyclic nucleotide pathways (cGMP, cAMP) and has been validated by experimental data.

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Dandekar, T., Friebe, A., Feil, R., Dittrich, M., Breitenbach, T., Englert, N., Osmanoglu, O., rukoyatkina, n., Wangorsch, G., Butt, E., Gambaryan, S.. 2021-02-03. cGMP signaling: probing antagonistic cyclic nucleotide platelet signals by modeling and experiment. https://doi.org/10.1101/2021.02.01.429103

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