Fig. 6.

Hypothetical model of regulatory mechanisms of PI3Kγ heterodimers. The scheme illustrates the activation processes of p87/p110γ (Left) and p101/p110γ (Right). Interaction of p101 with Gβγ is sufficient to translocate p101/p110γ to the plasma membrane as a prerequisite for its activation. In contrast, p87/p110γ is not translocated to the plasma membrane by Gβγ; instead, translocation of p87/p110γ is accomplished by the interaction of p110γ with Ras-GTP. Based on the requirement of Ras-dependent recruitment of p87/p110γ, Ras constitutes an indispensable activator in the activation process of this specific isoform. Following recruitment of PI3Kγ, both p87/p110γ and p101/p110γ are allosterically activated. Consistent with the present knowledge, these distinct mechanisms might be the basis for the specific regulation of different PI3Kγ-dependent cellular effects (see the text for details). The data presented here provide evidence of differential regulatory mechanisms of the 2 PI3Kγ heterodimers.