Both ligand- and cell-specific parameters control ligand agonism in a kinetic model of g protein-coupled receptor signaling.

ABSTRACT: G protein-coupled receptors (GPCRs) exist in multiple dynamic states (e.g., ligand-bound, inactive, G protein-coupled) that influence G protein activation and ultimately response generation. In quantitative models of GPCR signaling that incorporate these varied states, parameter values are often uncharacterized or varied over large ranges, making identification of important parameters and signaling outcomes difficult to intuit. Here we identify the ligand- and cell-specific parameters that are important determinants of cell-response behavior in a dynamic model of GPCR signaling using parameter variation and sensitivity analysis. The character of response (i.e., positive/neutral/inverse agonism) is, not surprisingly, significantly influenced by a ligand's ability to bias the receptor into a

SUBMITTER: Kinzer-Ursem TL 

PROVIDER: S-EPMC1769407 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature