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    J Theor Biol. 2010 Feb 21;262(4):679-90. Epub 2009 Oct 31.

    Modeling species-specific diacylglycerol dynamics in the RAW 264.7 macrophage.

    Callender HL, Horn MA, DeCamp DL, Sternweis PC, Alex Brown H.

    Source

    Department of Mathematics, Vanderbilt University, 1326 Stevenson Center, Nashville, TN 37240, USA. callende@up.edu

    Abstract

    A mathematical model of the G protein signaling pathway in RAW 264.7 macrophages downstream of P2Y(6) 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.

    (c) 2009 Elsevier Ltd. All rights reserved.

    PMID:
    19883664
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC2822135
    Free PMC Article

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