Figure 5.

A model of the proposed mechanism by which β-adrenoceptor activation may down-regulate MMP-9 expression. Following binding of an agonist to the β-adrenoceptor, there is an increase in intracellular cAMP levels and phosphorylation of the receptor by PKA or GRK. As a result of this, β-arrestin is recruited to the receptor. Agonist stimulation also activates PP2A and initiates formation of a tri-molecular complex with β-arrestin and the p65 subunit of NF-κB. The trimolecular complex then interacts with the NF-κB binding motif on the MMP-9 promoter to inhibit transcription in a non-classical manner.