Figure 6.

Schematic representation of the model for partially adapting PIP2 hydrolysis induced by the Gq pathway. Initial PIP2 hydrolysis upon Gq–GPCR activation is due to the formations of highly efficient Gαq_GTP–PLCβ–Gβγ sandwich complex. The subsequent partial adaptation (recovery) of the hydrolysis, indicated by the PIP2 synthesis, is due to the dissociation of Gβγ from this complex. Therefore, the steady-state partial PIP2 hydrolysis is primarily governed by the less-efficient Gαq_GTP–PLCβ complex. Injection of fresh Gβγ (from other GPCR pathways) converts Gαq_GTP–PLCβ to the sandwich complex, rescuing the PIP2 hydrolysis. The ability of Gβγ to stay bound to the PM is determined by the PM affinity of Gγ in the Gbγ dimer. Therefore, in the presence of Gβγ with high-PM affinity Gγ such as Gγ3, the PIP2 hydrolysis adaptation is slower than that of cells expressing low-PM affinity Gγ9. PIP2, phosphatidylinositol 4,5-bisphosphate; PLCβ, phospholipase C β.