Figure 5.

Summary of the mechanisms responsible for β₂AR down-regulation by CREB-mediated/let-7f processes in HASM cells. HASM cells express β₂AR at a stable level when receptor production and degradation are at an equilibrium. Upon agonist activation of β₂AR, intracellular cAMP levels increase due to receptor-G_s coupling. cAMP activates PKA, which in turn activates the CREB transcription factor. The transcription factor subsequently binds to the promoter of pri-let-7f, increasing expression of let-7f. Then let-7f binds to the 3′UTR of ADRB2 and represses translation, contributing to agonist-promoted long-term down-regulation of β₂AR. Another mechanism of down-regulation that is apparent in HASM cells is the degradation of β-arrestin–mediated internalized receptors.