FIGURE 6.

Role of the LL5β-Filamin A-SHIP2 complex during PtdIns(3,4,5)P₃-mediated directed migration. In directed migrating cells, PtdIns(3,4,5)P₃ accumulates in their leading edge. LL5β controls the spatial distribution and activity of Filamin A depending on the localization of membranous PtdIns(3,4,5)P₃ (shown as PIP₃). LL5β enhances lamellipodium formation by possibly increasing the cross-linking of newly polymerized F-actin at the plasma membrane (shown in red) by recruiting the F-actin-cross-linking molecule, Filamin A, to the plasma membrane. SHIP2 is co-recruited to sites of PtdIns(3,4,5)P₃ accumulation by LL5β via Filamin A, and then it reciprocally dephosphorylates PtdIns(3,4,5)P₃ to phosphatidylinositol 3,4-biphosphate (PtdIns(3,4)P₂, shown as PIP₂).