Figure 2. Model for the mechanistic basis of differential sensitivity of cells containing different γ subunits.

On activation, G proteins progress through two different paths: (i) when they contain a non-translocating γ subunit (left) or (ii) when they contain a translocating γ subunit (right). Left: the activated α and βγ remain on the plasma membrane. Since receptor activation requires the heterotrimer, this results in continual activation of Gαq reflected in a high level of PLCβ activation (multiple arrows). Right, the translocation of βγ away from the plasma membrane reduces the heterotrimer concentration and subsequent PLCβ stimulation. Although, we have been unable to obtain evidence for βγ activation of PLCβ in these cells (Text S2), this model is consistent with the results even if βγ activates PLCβ because βγ concentration available for PLCβ activation is lowered by translocation.