Modeling species-specific diacylglycerol dynamics in the RAW 264.7 macrophage

Hannah L. Callender, Mary Ann Horn, Dianne L. DeCamp, Paul C. Sternweis, H. Alex Brown

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

A mathematical model of the G protein signaling pathway in RAW 264.7 macrophages downstream of P2Y6 receptors activated by the ubiquitous signaling nucleotide uridine 5'-diphosphate is developed. The model, which is based on time-course measurements of inositol trisphosphate, cytosolic calcium, and diacylglycerol, focuses particularly on differential dynamics of multiple chemical species of diacylglycerol. When using the canonical pathway representation, the model predicted that key interactions were missing from the current network structure. Indeed, the model suggested that accurate depiction of experimental observations required an additional branch to the signaling pathway. An intracellular pool of diacylglycerol is immediately phosphorylated upon stimulation of an extracellular receptor for uridine 5'-diphosphate and subsequently used to aid replenishment of phosphatidylinositol. As a result of sensitivity analysis of the model parameters, key predictions can be made regarding which of these parameters are the most sensitive to perturbations and are therefore most responsible for output uncertainty.

Original languageEnglish (US)
Pages (from-to)679-690
Number of pages12
JournalJournal of Theoretical Biology
Volume262
Issue number4
DOIs
StatePublished - Feb 1 2010

Keywords

  • Cellular signaling pathways
  • Mathematical modeling
  • P2Y receptor
  • Sensitivity analysis
  • Uridine 5'-diphosphate

ASJC Scopus subject areas

  • Statistics and Probability
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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