Figure 7. Proposed functions of PP1 in IP₃R signalling.

Proposed model in which IP₃ competes with IRBIT for binding to the N-terminus of IP₃R (residues 1–604). Binding of IP₃ is favoured as it has a higher affinity for the IP₃R. The binding of IP₃ induces Ca²⁺ release from the ER (endoplasmic reticulum). Ca²⁺ can then activate the phosphorylation cascade on Ser⁶⁸, Ser⁷¹ and Ser⁷⁴. We propose that PKD, CaMKI/II/IV, AMPK and/or MK-2 are probable candidates to phosphorylate Ser⁶⁸ in response to Ca²⁺ release. PP1 is bound to the N-terminal KQIQF motif on IRBIT, and this binding of PP1 allows for efficient dephosphorylation of Ser⁶⁸. PP1 also directly interacts with the C-terminus of the IP₃R (residues 2590–2749) and indirectly via AKAP9 to the regulatory domain of the IP₃R.