Quantitative Modeling of GRK-Mediated β2AR Regulation
Figure 5
Simulated effects of phosphatase location and recycling of phosphorylated β2AR on receptor dephosphorylation.
HEK 293 cells stably overexpressing WT β2AR were treated for 5 min with 1 µM ISO (red bar) followed by washout and addition of 1 µM propranolol (blue bar). Experimental data [16] are shown as discrete points with standard errors and the simulations are shown as continuous lines. The black lines are the total phosphorylated receptor, red indicates the phosphorylated receptor on the plasma membrane and blue indicate internalized levels of phosphorylated β2AR. (A) Model A allows for dephosphorylation of both the internalized and plasma membrane bound receptor along with recycling of phosphorylated and dephosphorylated receptor. (B) Model B disallows plasma membrane dephosphorylation but allows both dephosphorylation of the internalized receptor and recycling of phosphorylated receptor. (C) Model C allows for dephosphorylation of both the internalized and plasma membrane bound receptor but limits recycling to only dephosphorylated receptor. (D) Model D allows for dephosphorylation only at the plasma membrane and also allows recycling of phosphorylated receptor. (E) Model E allows for dephosphorylation only at the plasma membrane and disallows recycling of phosphorylated receptor. (F) Model F allows for dephosphorylation only after internalization and prevents recycling of phosphorylated receptor.