Quantitative modeling of GRK-mediated beta2AR regulation.

ABSTRACT: We developed a unified model of the GRK-mediated beta2 adrenergic receptor (beta2AR) regulation that simultaneously accounts for six different biochemical measurements of the system obtained over a wide range of agonist concentrations. Using a single deterministic model we accounted for (1) GRK phosphorylation in response to various full and partial agonists; (2) dephosphorylation of the GRK site on the beta2AR; (3) beta2AR internalization; (4) recycling of the beta2AR post isoproterenol treatment; (5) beta2AR desensitization; and (6) beta2AR resensitization. Simulations of our model show that plasma membrane dephosphorylation and recycling of the phosphorylated receptor are necessary to adequately account for the measured dephosphorylation kinetics. We further used the model to predict th

SUBMITTER: Vayttaden SJ 

PROVIDER: S-EPMC2798957 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature