Figure 6. Model for interaction of PDE4D3 with mAKAP in vivo.
(A) Under resting conditions, PDE4D3 binds to the mAKAP signalling complex. (B) Upon hormonal stimulation of a cell, cAMP increases and activates mAKAP-bound PKA. The catalytic subunits phosphorylate local substrates, including PDE4D3. Phosphorylation of PDE4D3 on Ser-13 enhances the binding affinity of PDE4D3 for mAKAP. Phosphorylation of PDE4D3 on Ser-54 increases PDE activity 2-fold and causes cAMP breakdown. (C) With the return of basal cAMP levels, the PKA holoenzyme reforms. Phosphatase activity dephosphorylates PDE4D3, and the signalling system is reset.